Multiple SclerosisPhase 2OMS115102NCT00640328

Ofatumumab Dose-finding in Relapsing Remitting Multiple Sclerosis (RRMS) Patients

A Phase 2 study testing Ofatumumab 100, Ofatumumab 300 and Ofatumumab 700 in people with Multiple Sclerosis, run by GlaxoSmithKline.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The trial consists of a dose escalation, to establish the safety of ofatumumab in RRMS patients. A 48-week treatment period followed by an individualized follow-up period until normalization of peripheral B-cell counts or Immunoglobulin G (IgG) levels. Read more about this study

Who is it for?: Ages 18 to 55 years
Conditions the study is for: Multiple Sclerosis
What is being tested?: Ofatumumab 100, Ofatumumab 300 and Ofatumumab 700
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 38 participants
Where: No sites listed yet
Study dates: May 2008to Oct 2011
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Patients with definite diagnosis of relapsing-remitting MS according to McDonald criteria
Patients with:
At least two confirmed relapses within the last 24 months or
At least one confirmed relapse within the last 12 months or
One confirmed relapse between 12 and 24 months prior to screening, and at least one documented T1 Gd-enhancing lesion on an MRI performed within 12 months prior to screening.
Patients with disability equivalent to Expanded Disability Status Scale (EDSS) score of 0-5.0 (both included) at screening

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Neurologically stable patients with no evidence of relapse for at least 30 days prior to start of Screening and during the Screening Phase
Female patients must be either post-menopausal, surgically incapable of bearing children or practicing an acceptable method of birth control e.g. hormonal contraceptives, intrauterine device, spermicide and barrier as long as they are on trial medication and for a period of 1 year following the last infusion of trial drug. Females of childbearing potential must have a negative pregnancy test at screening visit prior to entry into the treatment period
Following receipt of verbal and written information about the trial, the patient must provide signed informed consent before any trial related activity is carried out.

Who cannot join

Diagnosis of Secondary Progressive Multiple Sclerosis (SPMS), Primary Progressive Multiple Sclerosis (PPMS) or Progressive Relapsing Multiple Sclerosis (PRMS) or Neuromyelitis optica
Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) or confirmed PML
Findings on brain MRI scan indicating any other clinically significant brain abnormality other than MS
Patients unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media) or who lack adequate peripheral venous access
Patients who have had the following treatments:
Lymphocyte-depleting therapies (e.g. alemtuzumab (Campath®), anti-Cluster of Differentiation (CD4), cladribine, total body irradiation, bone marrow transplantation), mitoxantrone or cyclophosphamide at any time

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Anti-CD20 treatments or any monoclonal antibodies at any time
Immunoglobulin, azathioprine, cyclosporine, tacrolimus or other immunosuppressive agents, immunomodulatory agents or plasma exchange within six months prior to randomization in the trial apart from Glatiramer Acetate and Interferon Beta (IFN-b).
Glatiramer Acetate or IFN-b within three months prior to the randomization in the trial.
Glucocorticoids or Adrenocorticotropic Hormone (ACTH) within one month prior to the screening in the trial.
Receipt of a live vaccine within one month prior to screening in the trial.
Plasmapheresis for treatment of relapses within 2 months prior to randomization in the trial.
Initiation of therapy with Statins or hormone replacement treatment within one month or less prior to screening in the trial.
Patients who have received other disease modifying therapies for MS may be allowed on a case to case basis after discussion with the sponsors medical monitor
Past or current history of medically significant adverse effects (including allergic reactions) from:
Cetirizine
Prednisolone
Paracetamol/acetaminophen
Plasma proteins or a known hypersensitivity to components of the investigational product.
Past or current malignancy, except for
Cervical carcinoma Stage 1B or less
Non-invasive basal cell and squamous cell skin carcinoma
Cancer diagnoses with a complete response of a duration of > 5 years. Patients with a prior history of hematological malignancies are excluded regardless of response
Clinically significant cardiac disease, including acute myocardial infarction within six months from screening, unstable angina, congestive heart failure, previous venous or arterial thrombosis or arrhythmia requiring therapy.
Electrocardiogram (ECG) showing significant abnormality that the treating investigator determines may jeopardize the subject's health (i.e. acute ischemia, left bundle branch or bifascicular block)
Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, immunodeficiency syndrome, pulmonary, cerebral, psychiatric or neurological disease which may impair their reliable participation in the trial or necessitate the use of medication not allowed by this protocol.
History of severe, clinically significant Central Nervous System (CNS) trauma (e.g. cerebral contusion, spinal cord compression) or a history or presence of myelopathy due to spinal cord compression by disk or vertebral disease
Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. Any previous serious infections should be discussed with the sponsors medical monitor (e.g. opportunistic or atypical infections)
Female patients who are pregnant or nursing.
Use of an investigational drug or other experimental therapy for a condition other than MS within 4 weeks prior to screening. Any prior use of an investigational drug or other experimental therapy for MS at any time should be discussed with the medical monitor.
Current participation in any other interventional clinical trial. Participation in non-interventional trial requires approval of the protocol by the sponsor
Serum vitamin B12 below lower limit of normal
Positive polymerase chain reaction (PCR) screening for John Cunningham Virus (JC Virus) as measured by qualitative plasma and/or white blood cell JCV DNA
Serologic evidence of Hepatitis B (HB) infection based on the results of testing for Hepatitis B Surface Antigen (HBsAg), anti- Hepatitis B Core (HBc) and anti- Hepatitis B Surface (HBs) antibodies with eligibility based on the results as follows:
Patients positive for HBsAg are excluded
Patients negative for HBsAg but positive for both anti-HBc and anti-HBs antibodies (indicating past infection) are eligible
Patients negative for HBsAg and anti-HBc antibody but positive for anti-HBs antibody (indicating past vaccination) are eligible
Patients negative for HBsAg and anti-HBs antibody but positive for anti-HBc antibody will require clarification of their status by testing for HB DNA, which if positive will exclude the patient from participation
Patient with documented vaccination against Hepatitis B (primary and secondary immunization and booster) will be considered eligible for the trial.
Positive serology for HIV
Screening laboratory values:
White Blood Cell (WBC) < 3.0 x 109/L
Neutrophils < 2 x 109/L
Platelets < 100 x 109/L
Circulating IgG level < lower limit of normal (according to central laboratory range)
Serum Alanine Aminotransferase (S-ALAT) > 2.5 times the upper limit of normal (according to central laboratory range)
Serum Alpha Fetoprotein (S-AP) > 2.0 times the upper limit of normal (according to central laboratory range)
Serum Aspartate Aminotransferase (ASAT) >3.0 times the upper limit of normal (according to central laboratory range)
Bilirubin > 1.5 times the upper limit of normal (according to central laboratory range)
S-creatinine > the upper limit of normal (according to central laboratory range)
CD4 count <500 cells/mm3, CD4:CD8 <0.9
Patients known or suspected of not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychological disorder).
Positive test for Hepatitis C antibody confirmed with a Hepatitis C real time (RT) PCR assay.
Patients who are positive for Hepatitis C antibody and negative when the Hepatitis C RT PCR assay is performed will be eligible for the study. Patients who are positive for Hepatitis C antibody and have a positive or indeterminate result when the Hepatitis C RT PCR assay is performed will not be eligible for the study.
Positive test results for tuberculosis using the QuantiFERON test and/or Chest X-ray findings suggestive of tuberculosis (TB). For patients who have had a Chest X-ray performed within the past 6 months without any findings indicative of TB, QuantiFERON test alone may be performed.

About this study

Official title: A Double-blind, Randomized, Placebo Controlled, Multicenter, Dose-finding Trial of Ofatumumab in Relapsing Remitting Multiple Sclerosis (RRMS) Patients

Read the detailed description

The trial consists of two phases, a 48 week treatment period, followed by an individualized treatment period of up to two years.

Patients are treated in cohorts of increasing doses (100 mg, 300 mg and 700 mg) with 12 patients in each dose cohort. Within each cohort patients are randomized asymmetrically in a 2:1 ratio such that eight patients will receive ofatumumab and four patients will receive placebo. After 24 weeks the patients randomized to placebo will be treated with the active dose for the cohort. For blinding purposes, patients randomized to the active dose will be treated with placebo after 24 weeks. Thus, each patient will receive two administrations of trial product with 24 weeks follow-up resulting in a total treatment period of 48 weeks duration. An Independent Data Monitoring Committee (IDMC) will review and evaluate the safety data of each cohort, a minimum of 4 weeks data including the week 4 Magnetic Resonance Imaging (MRI) from at least 10 patients, to consider if progression to the next higher dose cohort is acceptable.

The trial product is administered as two infusions separated by two weeks. Clinical assessment and Gadolinium enhanced (Gd-enhanced) MRI scan will be performed at weeks -4, 0, 2, 4, and every 4 weeks until week 48. The MRI scan at week 2 is carried out for safety assessment prior to administering the second infusion in the first treatment course. When patients in all dose cohorts have been dosed and have had week 4 MRI scans performed, an IDMC will review all available safety data.

After completion of week 48 patients will be followed to monitor B-cell and IgG normalization. B-cell levels will be monitored every 12 weeks until CD19+ cells have returned to baseline level (Visit 3) or normalized level. If the B-cell levels are not normalized after two years the patient should be followed until either the IgG or the B-cell levels are normalized (see Section 9.2.4 for details). During this period Gd-enhanced MRI follow up scans will be performed every 12 weeks to evaluate potential rebound, safety and for Progressive Multifocal Leukoencephalopathy (PML) monitoring.

Conditions: Multiple Sclerosis
Being tested: Ofatumumab 100, Ofatumumab 300, Ofatumumab 700, Placebo
Keywords: relapsing forms of multiple sclerosis, ofatumumab, multiple sclerosis
Medical subject headings: Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Ofatumumab 100Drug
100mg
Ofatumumab 300Drug
300mg
Ofatumumab 700Drug
700mg
PlaceboDrug
matching placebo

Study groups in NCT00640328
Study group	Role	What they receive
Cohort 1.1	Experimental	100mg ofatumumab then placebo Receives: Drug: Ofatumumab 100; Drug: Placebo
Cohort 1.2	Experimental	placebo then 100mg ofatumumab Receives: Drug: Ofatumumab 100; Drug: Placebo
Cohort 2.1	Experimental	300mg ofatumumab then placebo Receives: Drug: Ofatumumab 300; Drug: Placebo
Cohort 2.2	Experimental	placebo then 300mg ofatumumab Receives: Drug: Ofatumumab 300; Drug: Placebo
Cohort 3.1	Experimental	700mg ofatumumab then placebo Receives: Drug: Ofatumumab 700; Drug: Placebo
Cohort 3.2	Experimental	placebo then 700mg ofatumumab Receives: Drug: Ofatumumab 700; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Any Adverse Event
An Adverse Event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A list of all adverse events is reported in the "Other (Non-Serious) Adverse Events" section. Non-serious AEs were not collected during the Individualized Follow-up Period.
Measured: First Treatment Period (FTP): From Visit 3 (Week 0) up to Visit 10 (Week 24); Second Treatment Period (STP): From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Number of Participants With the Indicated Critical Adverse Events (CAEs)
A CAE=treatment-related (TR) grade (G) >=3 AE on day of infusion (inf.) preventing inf. to be resumed, a TR G 3 bronchospasm during 1 inf., an AE whose severity becomes G 3 for the third time during 1 inf., infections reported as serious, a TR neurological event consistent with progressive multifocal leukoencephalopathy (PML), any malignancy, and any fatal adverse drug reaction. AE severity (assessed as G 1-5) was classified using the Common Terminology Criteria for Adverse Events v3.0: G 1=mild AE; G 2=moderate AE; G 3=severe AE; G 4=life-threatening or disabling AE; G 5=death related to AE.
Measured: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Number of Participants With Negative or Unconfirmed Human Anti-human Antibodies (HAHA) in Which Concentrations of Ofa Were Below 500 Nanograms Per Milliliter (ng/ml)
Participants are checked for negative (or a lack of) HAHA at Baseline, and then throughout the study, to ensure that the investigational product is not causing HAHA development. Participants with concentrations of Ofa that are missing or are above 500 nanograms per milliliter (ng/mL) are considered to have unconfirmed HAHA results.
Measured: Visit 3 (Week 0), Visit 10 (Week 24), Visit 17 (Week 48) or early withdrawal (EW), and Visit 26 (Week 104)
Number of Participants With Abnormal Physical Examination Findings
The investigator performed the physical examination, which included but was not limited to: general appearance and the following body systems: lymph nodes, mouth and throat, lungs, cardiovascular, abdomen, extremities, muscular-skeletal, neurological (apart from multiple sclerosis [a brain and spinal cord disease]), and skin. All abnormal clinically relevant findings such as vein problems (venous varices), disorder of the vertebral column (vertebropathy), increased hearing loss, post operative mark (scar), and chronic skin disorder with no sweat and itching (anhidrotic eczema) were reported.
Measured: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelet Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for hematology assessment. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in basophils, eosinophils, leukocytes, monocytes, lymphocytes, neutrophils, and platelets count was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Week 104 for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Erythrocyte Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for assessment of erythrocyte count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in erythrocyte count was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hematocrit at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for hematocrit assessment. Hematocrit is the percentage of blood volume (BV) that is occupied by red blood cells (RBCs). Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in hematocrit was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline. Hematocrit is measured as a percentage, i.e., volume (V) of red blood cells per volume of blood.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hemoglobin Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for assessment of hemoglobin count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in hemoglobin was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Albumin at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for assessment of albumin count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 104 for the IFUP) in albumin was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: VIsit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Transaminase (ALT) at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for the assessment of alkaline phosphatase, AST, and ALT. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Bicarbonate, Glucose, Potassium, Sodium, and Urea at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for the assessment of bicarbonate, glucose, potassium, and urea. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP,Week 24 for the STP, and Week 0 for the IFUP) in Bilirubin and Creatinine at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for the assessment of bilirubin and creatinine. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Immunoglobins at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Blood samples of participants were collected for the assessment of antibodies produced by B-cells (immunoglobins): immunoglobulin A, immunoglobin G, and immunoglobin M. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Blood Pressure (BP) at Week 24 (FTP) and Week 48 (STP)
Maximum (systolic) and minimum (diastolic) BP were assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Pulse Rate at Week 24 (FTP) and Week 48 (STP)
The pulse rate of each participant was assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Temperature at Week 24 (FTP) and Week 48 (STP)
The temperature of each participant was assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Complement Activation (CH50) at Week 24 (FTP) and Week 48 (STP)
Blood samples of participants were collected for CH50 prior to and 2 hours after dosing, and the samples were sent to a Central Laboratory for analysis: Bio Analytical Research Corporation (BARC). Change from Baseline (Week 0 for the FTP; Week 24 for the STP) was calculated as the value at Weeks 24 (FTP) and 48 (STP) minus the value at Baseline. Ofa depletes (induces the cell death of) B cells. When Ofa binds to a B cell, it induces complement CH50, which in turn causes cell death via cytotoxicity. Therefore, the CH50 levels were measured to ensure that CH50 was being appropriately activated.
Measured: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)

Secondary outcomes (9)

Number of the Indicated Types of Lesions (Ls) Assessed Per Magnetic Resonance Imaging (MRI)
The MRI scan was performed prior to dosing and could be performed up to 4 days prior to Visits 3 and 10. An IDMC reviewed the data. T1 enhancing Ls are enhanced by gadolinium, are considered representative of disease activity/inflammation, and may signify a relapse. Measurement of these Ls is comparative from visit to visit. "Total T1 enhancing Ls" represent the total of the new T1 enhancing Ls over the entire study period. T2 L measurements measure all Ls on the brain in terms of volume and size, measuring for new or enlarging Ls. T1 hypointensive Ls are areas of permanent damage.
Measured: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Total Volume of T2 Lesions at Week 24 and Week 48
The MRI scan should be performed prior to dosing and can be performed up to 4 days prior to Visits 3 and 10. An IDMC reviewed the data. The volume of T2 lesions was not a cumulative volume, but the volume measured at Visit 10 and Visit 17. T2 lesion measurements measure all lesions on the brain in terms of volume and size, measuring for new lesions or enlarging lesions.
Measured: Visit 10 (Week 24) and Visit 17 (Week 48)
Ofa Drug Concentration After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) Intravenous (i.v.) Infusions
The peripheral blood for each participant was collected and analyzed for the concentration of the drug in serum. There were four infusions in the study; the third infusion at Visit 10 represents the first infusion of the second treatment period (Weeks 24-48). Data are presented for the predose concentrations.
Measured: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion.
The Maximum Observed Plasma Concentration (Cmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions
The peripheral blood for each participant was collected and analyzed for Cmax after the first, second, third, and fourth i.v. infusions. Assessment was performed using the noncompartmental method (this analysis is highly dependent on the estimation of total drug exposure).
Measured: Visit 3 (Week 0), Visit 4, (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion.
The Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point (AUC(0-t)) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions
The peripheral blood for each participant was collected and analyzed to estimate the area under the plasma concetration-time curve, AUC(0-t), and was assessed using the non-compartmental method.
Measured: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour (hr) after infusion, and 2 hours after infusion.
Time to Reach Cmax (Tmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions
The peripheral blood for each participant was collected and analyzed for tmax.
Measured: Visit 3 (Week 0), Visit 4 (Week 2),Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion.
Clearance of Ofa Over the Course of Weeks 0-2 and 24-26
The peripheral blood for each participant was collected and analyzed for clearance. Clearance is the measure of efficiency with which a drug is irreversibly removed form the body. The average clearance over the course of Weeks 0-2 and 24-26 is reported.
Measured: Weeks 0-2 and 24-26
The Volume of Distribution at Steady State (Vss) of Ofatumumab Over the Course of Weeks 0-2 and 24-26
The peripheral blood for each participant was collected and analyzed for Vss. The average Vss over the course of Weeks 0-2 and 24-26 is reported.
Measured: Weeks 0-2 and 24-26
Half Life (t1/2) of Ofatumumab in the Terminal Elimination Phase Over the Course of Weeks 0-2 and 24-26
The peripheral blood for each participant was collected and analyzed for half life. Half life is defined as the period of time required for the amount of drug in the body to be reduced by half. The average t1/2 over the course of Weeks 0-2 and 24-26 is reported.
Measured: Weeks 0-2 and 24-26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2008Oct 2011

First posted21 Mar 2008 (estimated)
Study startMay 2008
Primary completionMay 2010
Study completionOct 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Multiple SclerosisStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 38 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00640328
Sponsor's protocol ID: 115102
Acronym: OMS115102
Status last verified: Mar 2017
First submitted: 18 Mar 2008
Last updated: 11 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 3
An Extension Study of Ublituximab in Participants With Relapsing Multiple Sclerosis
Relapsing Multiple Sclerosis (RMS)
RecruitingObservational study
A Study Evaluating the Real World Experience of Participants Treated With BRIUMVI® (Ublituximab-xiiy) for Relapsing Multiple Sclerosis (RMS)
Relapsing Multiple Sclerosis, Multiple Sclerosis
RecruitingObservational study
Non-interventional Study of Subcutaneous Ocrelizumab in Persons With Relapsing-Remitting Multiple Sclerosis
Relapsing-Remitting Multiple Sclerosis
RecruitingPhase 2
A Phase 2a Study of SUN-627 in Participants With Non-Active Secondary Progressive and Primary Progressive Multiple Sclerosis (SPMS/PPMS)
Primary Progressive Multiple Sclerosis, Primary Progressive MS
RecruitingPhase 4
A Study of Ocrelizumab Administered Subcutaneously in Participants With Multiple Sclerosis Who Switch From an Approved Anti-CD20 Therapy
Multiple Sclerosis

All Multiple Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Randomized, Placebo Controlled, Multicenter, Dose-finding Trial of Ofatumumab in Relapsing Remitting Multiple Sclerosis (RRMS) Patients
ClinicalTrials.gov ID: NCT00640328
Acronym / sponsor ID: OMS115102 / 115102
Conditions: Multiple Sclerosis
Keywords: relapsing forms of multiple sclerosis, ofatumumab, multiple sclerosis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 38 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: May 2008
Primary completion: May 2010 (actual)
Study completion: Oct 2011 (actual)
First posted: 21 Mar 2008 (estimated)
Results: Posted 4 Dec 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The trial consists of two phases, a 48 week treatment period, followed by an individualized treatment period of up to two years.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 6

Arm	Type	Receives
Cohort 1.1	Experimental	Drug: Ofatumumab 100, Drug: Placebo100mg ofatumumab then placebo
Cohort 1.2	Experimental	Drug: Ofatumumab 100, Drug: Placeboplacebo then 100mg ofatumumab
Cohort 2.1	Experimental	Drug: Ofatumumab 300, Drug: Placebo300mg ofatumumab then placebo
Cohort 2.2	Experimental	Drug: Ofatumumab 300, Drug: Placeboplacebo then 300mg ofatumumab
Cohort 3.1	Experimental	Drug: Ofatumumab 700, Drug: Placebo700mg ofatumumab then placebo
Cohort 3.2	Experimental	Drug: Ofatumumab 700, Drug: Placeboplacebo then 700mg ofatumumab

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Patients with definite diagnosis of relapsing-remitting MS according to McDonald criteria
Patients with:
At least two confirmed relapses within the last 24 months or
At least one confirmed relapse within the last 12 months or
One confirmed relapse between 12 and 24 months prior to screening, and at least one documented T1 Gd-enhancing lesion on an MRI performed within 12 months prior to screening.

Key exclusion criteria (55 listed)

Diagnosis of Secondary Progressive Multiple Sclerosis (SPMS), Primary Progressive Multiple Sclerosis (PPMS) or Progressive Relapsing Multiple Sclerosis (PRMS) or Neuromyelitis optica
Neurological findings consistent with Progressive Multifocal Leukoencephalopathy (PML) or confirmed PML
Findings on brain MRI scan indicating any other clinically significant brain abnormality other than MS
Patients unable to undergo MRI scans (e.g. due to pacemaker, severe claustrophobia, hypersensitivity to contrast media) or who lack adequate peripheral venous access
Patients who have had the following treatments:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ofatumumab 100100mg	Drug	Cohort 1.1, Cohort 1.2
Ofatumumab 300300mg	Drug	Cohort 2.1, Cohort 2.2
Ofatumumab 700700mg	Drug	Cohort 3.1, Cohort 3.2
Placebomatching placebo	Drug	Cohort 1.1, Cohort 1.2, Cohort 2.1, Cohort 2.2, Cohort 3.1, Cohort 3.2

Primary outcome

Number of Participants With Any Adverse Event
Time frame: First Treatment Period (FTP): From Visit 3 (Week 0) up to Visit 10 (Week 24); Second Treatment Period (STP): From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
An Adverse Event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A list of all adverse events is reported in the "Other (Non-Serious) Adverse Events" section. Non-serious AEs were not collected during the Individualized Follow-up Period.
Number of Participants With the Indicated Critical Adverse Events (CAEs)
Time frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
A CAE=treatment-related (TR) grade (G) >=3 AE on day of infusion (inf.) preventing inf. to be resumed, a TR G 3 bronchospasm during 1 inf., an AE whose severity becomes G 3 for the third time during 1 inf., infections reported as serious, a TR neurological event consistent with progressive multifocal leukoencephalopathy (PML), any malignancy, and any fatal adverse drug reaction. AE severity (assessed as G 1-5) was classified using the Common Terminology Criteria for Adverse Events v3.0: G 1=mild AE; G 2=moderate AE; G 3=severe AE; G 4=life-threatening or disabling AE; G 5=death related to AE.
Number of Participants With Negative or Unconfirmed Human Anti-human Antibodies (HAHA) in Which Concentrations of Ofa Were Below 500 Nanograms Per Milliliter (ng/ml)
Time frame: Visit 3 (Week 0), Visit 10 (Week 24), Visit 17 (Week 48) or early withdrawal (EW), and Visit 26 (Week 104)
Participants are checked for negative (or a lack of) HAHA at Baseline, and then throughout the study, to ensure that the investigational product is not causing HAHA development. Participants with concentrations of Ofa that are missing or are above 500 nanograms per milliliter (ng/mL) are considered to have unconfirmed HAHA results.
Number of Participants With Abnormal Physical Examination Findings
Time frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
The investigator performed the physical examination, which included but was not limited to: general appearance and the following body systems: lymph nodes, mouth and throat, lungs, cardiovascular, abdomen, extremities, muscular-skeletal, neurological (apart from multiple sclerosis [a brain and spinal cord disease]), and skin. All abnormal clinically relevant findings such as vein problems (venous varices), disorder of the vertebral column (vertebropathy), increased hearing loss, post operative mark (scar), and chronic skin disorder with no sweat and itching (anhidrotic eczema) were reported.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Basophils, Eosinophils, Leukocytes, Monocytes, Lymphocytes, Neutrophils, and Platelet Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Blood samples of participants were collected for hematology assessment. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in basophils, eosinophils, leukocytes, monocytes, lymphocytes, neutrophils, and platelets count was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Week 104 for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Erythrocyte Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Blood samples of participants were collected for assessment of erythrocyte count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in erythrocyte count was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hematocrit at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Blood samples of participants were collected for hematocrit assessment. Hematocrit is the percentage of blood volume (BV) that is occupied by red blood cells (RBCs). Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in hematocrit was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline. Hematocrit is measured as a percentage, i.e., volume (V) of red blood cells per volume of blood.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Hemoglobin Count at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: Visit 26 (Week 104)
Blood samples of participants were collected for assessment of hemoglobin count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in hemoglobin was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Albumin at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: VIsit 26 (Week 104)
Blood samples of participants were collected for assessment of albumin count. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 104 for the IFUP) in albumin was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Alkaline Phosphatase, Aspartate Aminotransferase (AST), and Alanine Transaminase (ALT) at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Blood samples of participants were collected for the assessment of alkaline phosphatase, AST, and ALT. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Bicarbonate, Glucose, Potassium, Sodium, and Urea at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Blood samples of participants were collected for the assessment of bicarbonate, glucose, potassium, and urea. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP,Week 24 for the STP, and Week 0 for the IFUP) in Bilirubin and Creatinine at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Blood samples of participants were collected for the assessment of bilirubin and creatinine. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) in Immunoglobins at Week 24 (FTP), Week 48 (STP), and Week 104 (IFUP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Blood samples of participants were collected for the assessment of antibodies produced by B-cells (immunoglobins): immunoglobulin A, immunoglobin G, and immunoglobin M. Change from Baseline (Week 0 for the FTP, Week 24 for the STP, and Week 0 for the IFUP) was calculated as the value at Visit 10 (Week 24) for the FTP, the value at Visit 17 (Week 48) for the STP, and the value at Visit 26 (Week 104) for the IFUP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Blood Pressure (BP) at Week 24 (FTP) and Week 48 (STP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
Maximum (systolic) and minimum (diastolic) BP were assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Pulse Rate at Week 24 (FTP) and Week 48 (STP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
The pulse rate of each participant was assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Temperature at Week 24 (FTP) and Week 48 (STP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
The temperature of each participant was assessed prior to infusion. Change from Baseline (Week 0 for the FTP and Week 24 for the STP) was calculated as the value at Visit 10 (Week 24) for the FTP and the value at Visit 17 (Week 48) for the STP minus the value at Baseline.
Change From Baseline (Week 0 for the FTP and Week 24 for the STP) in Complement Activation (CH50) at Week 24 (FTP) and Week 48 (STP)
Time frame: FTP: Visit 3 (Week 0) and Visit 10 (Week 24); STP: Visit 10 (Week 24) and Visit 17 (Week 48)
Blood samples of participants were collected for CH50 prior to and 2 hours after dosing, and the samples were sent to a Central Laboratory for analysis: Bio Analytical Research Corporation (BARC). Change from Baseline (Week 0 for the FTP; Week 24 for the STP) was calculated as the value at Weeks 24 (FTP) and 48 (STP) minus the value at Baseline. Ofa depletes (induces the cell death of) B cells. When Ofa binds to a B cell, it induces complement CH50, which in turn causes cell death via cytotoxicity. Therefore, the CH50 levels were measured to ensure that CH50 was being appropriately activated.

9 secondary outcomes

Number of the Indicated Types of Lesions (Ls) Assessed Per Magnetic Resonance Imaging (MRI)
Time frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)
Total Volume of T2 Lesions at Week 24 and Week 48
Time frame: Visit 10 (Week 24) and Visit 17 (Week 48)
Ofa Drug Concentration After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) Intravenous (i.v.) Infusions
Time frame: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion.
The Maximum Observed Plasma Concentration (Cmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions
Time frame: Visit 3 (Week 0), Visit 4, (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion.
The Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Time Point (AUC(0-t)) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions
Time frame: Visit 3 (Week 0), Visit 4 (Week 2), Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour (hr) after infusion, and 2 hours after infusion.
Time to Reach Cmax (Tmax) After the First (Visit 3), Second (Visit 4), Third (Visit 10), and Fourth (Visit 11) i.v. Infusions
Time frame: Visit 3 (Week 0), Visit 4 (Week 2),Visit 10 (Week 24), and Visit 11 (Week 26). Samples were drawn predose, immediately following the end of infusion, 10 minutes after infusion, 1 hour after infusion, and 2 hours after infusion.
Clearance of Ofa Over the Course of Weeks 0-2 and 24-26
Time frame: Weeks 0-2 and 24-26
The Volume of Distribution at Steady State (Vss) of Ofatumumab Over the Course of Weeks 0-2 and 24-26
Time frame: Weeks 0-2 and 24-26
Half Life (t1/2) of Ofatumumab in the Terminal Elimination Phase Over the Course of Weeks 0-2 and 24-26
Time frame: Weeks 0-2 and 24-26

Results and safety

Results posted to the registry on 4 Dec 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo	8	8
300 mg Ofa/Matching Placebo	11	10
700 mg Ofa/Matching Placebo	7	7
Matching Placebo/100 mg Ofa	4	4
Matching Placebo/300 mg Ofa	4	4
Matching Placebo/700 mg Ofa	4	4

Primary outcome: Number of Participants With Any Adverse Event

Time frame: First Treatment Period (FTP): From Visit 3 (Week 0) up to Visit 10 (Week 24); Second Treatment Period (STP): From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104). Number. Unit: participants

Measure	100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo n = 8	300 mg Ofa/Matching Placebo n = 11	700 mg Ofa/Matching Placebo n = 7	Matching Placebo/100 mg Ofa n = 4	Matching Placebo/300 mg Ofa n = 4	Matching Placebo/700 mg Ofa n = 4
Weeks 0-24	8	10	7	3	2	2
Weeks 24-48	4	5	4	3	4	4
Individualized Follow-up Period	0	0	0	0	0	0

Population analysed: Full Analysis Set (FAS): all participants who had been exposed to the investigational product (IP) irrespective of their compliance to the planned course of treatment.

Primary outcome: Number of Participants With the Indicated Critical Adverse Events (CAEs)

Time frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104). Number. Unit: participants

Measure	300 mg Ofa/Matching Placebo n = 11	Matching Placebo/100 mg Ofa n = 4
Week 0-24; Influenza	0	1
Week 0-24; Bronchospasm	1	0
Week 0-24; Cough	1	0
Week 0-24; Rash pruritic	1	0
Week 24-48; any CAE	0	0
Individualized Follow-up Period; any CAE	0	0

Population analysed: FAS

Primary outcome: Number of Participants With Negative or Unconfirmed Human Anti-human Antibodies (HAHA) in Which Concentrations of Ofa Were Below 500 Nanograms Per Milliliter (ng/ml)

Time frame: Visit 3 (Week 0), Visit 10 (Week 24), Visit 17 (Week 48) or early withdrawal (EW), and Visit 26 (Week 104). Number. Unit: participants

Measure	100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo n = 8	300 mg Ofa/Matching Placebo n = 11	700 mg Ofa/Matching Placebo n = 7	Matching Placebo/100 mg Ofa n = 4	Matching Placebo/300 mg Ofa n = 4	Matching Placebo/700 mg Ofa n = 4
Week 0; n=8, 8, 2, 4, 3, 4	8	8	2	4	3	4
Week 24; n=8, 9, 1, 4, 4, 4	8	9	1	4	4	4
Week 48 or EW, negative; n=8, 11, 7, 4, 3, 4	8	11	7	4	3	1
Week 48 or EW, unconfirmed, n=8, 11, 7, 4, 3, 4	0	0	0	0	0	3
IFUP, n=8, 11, 7, 4, 4, 4	0	0	0	0	0	0

Population analysed: FAS. Only those participants contributing data at the indicated time points were analyzed (reflected by "n=" in the category titles).

Primary outcome: Number of Participants With Abnormal Physical Examination Findings

Time frame: FTP: From Visit 3 (Week 0) up to Visit 10 (Week 24); STP: From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104). Number. Unit: participants

Measure	100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo n = 8	700 mg Ofa/Matching Placebo n = 7	Matching Placebo/700 mg Ofa n = 4
Week 0-24; Venous varices on legs	1	0	0
Week 0-24; Vertebropathy	1	0	0
Week 0-24; Obesitas	1	0	0
Week 0-24; Increased hearing loss	0	1	0
Week 0-24; Post operative scar	0	1	0
Week 0-24; Anhidrotic eczema	0	0	1
Week 24-48; Venous varices on legs	1	0	0
Week 24-48; Vertebropathy	1	0	0

Population analysed: FAS

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Serious adverse events (SAEs) and non-serious AEs are reported for both the first period (FP; Weeks 0-24) and the second period (SP; Weeks 24-48). SAEs were collected during the IFUP (collected/reported up to Week 104); however, non-serious AEs were not.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
100 Milligrams (mg) Ofatumumab (Ofa)/Matching Placebo	0 of 8 (0%)	8 of 8 (100%)	Not reported
300 mg Ofa/Matching Placebo	2 of 11 (18.2%)	10 of 11 (90.9%)	Not reported
700 mg Ofa/Matching Placebo	0 of 7 (0%)	7 of 7 (100%)	Not reported
Matching Placebo/100 mg Ofa	1 of 4 (25%)	3 of 4 (75%)	Not reported
Matching Placebo/300 mg Ofa	0 of 4 (0%)	4 of 4 (100%)	Not reported
Matching Placebo/700 mg Ofa	0 of 4 (0%)	4 of 4 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ofatumumab 100, Ofatumumab 300 and Ofatumumab 700 in people with Multiple Sclerosis, run by GlaxoSmithKline.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 55 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Any Adverse Event (time frame: First Treatment Period (FTP): From Visit 3 (Week 0) up to Visit 10 (Week 24); Second Treatment Period (STP): From Visit 10 (Week 24) up to Visit 17 (Week 48); IFUP: up to Visit 26 (Week 104)). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00640328.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2017.