Multiple SclerosisPhase 1/2NCT01517282
Phase Ib Study to Evaluate MOR103 in Multiple Sclerosis
A Phase 1/2 study testing MOR103 in people with Multiple Sclerosis, run by MorphoSys AG at 5 sites in 3 countries.
Trial summary
Multiple sclerosis (MS) is a chronic inflammatory disease associated with central nervous system (CNS) demyelination and subsequent axonal degeneration. Multiple sclerosis exhibits an unpredictable and variable clinical course. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- MOR103
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 5 sitesin 3 countries
- Study dates
- Jan 2012to Feb 2014
- Phase
- Phase 1/2
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Outpatients with a diagnosis of RRMS or SPMS, who are currently not being treated and who have at least 1 of the following:
- At least 1 documented relapse within 1 year before Screening, or
- Two documented relapses within the past 2 years before Screening, or
- A new gadolinium (Gd)-enhancing lesion on magnetic resonance imaging (MRI) T1-weighted imaging within 1 year before Screening, or
- A new T2 lesion on MRI within 1 year before Screening. The patient must have 10 or less, Gd-enhancing lesions per T1-weighted MRI at Screening as assessed by a central reader.
- The patient must be able and willing to ambulate, with an Expanded Disability Status Scale (EDSS) score of ≥ 2.0 and ≤ 6.5 at both the Screening Visit and the Baseline Visit
Who cannot join
- A patient with primary progressive MS (PPMS)
- A patient who has previously received at any time any of the following
- B-cell or T-cell depleting therapies
- Cytotoxic agents, any immunosuppressive/immunomodulating agents
- A patient who has not stabilized, in the opinion of the investigator
- A patient with any medical condition or uncontrolled disease states other than MS requiring or likely to require systemic treatment with corticosteroids or other immune compromising agents
Show all 12Show fewer
- A patient with current or a history of major chronic inflammatory autoimmune diseases other than MS
- A patient with any type of infection
- Patients on chronic prophylactic or suppressive antibiotic, antifungal,or antiviral agents
- A patient with a history of tuberculosis.
- A patient with any signs of excretory hepatic or kidney dysfunction
- A patient with a positive test for Hepatitis B or Hepatitis C
Trial locations and contacts
5 sites in 3 countries.
5 sites in 3 countries
Poland2 sites
Morphosys Investigative Site
Gdansk
Morphosys Investigative Site
Poznan
United Kingdom2 sites
Morhosys Investigative Site
Manchester
MorphoSys Investigative Site
Nottingham
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Phase Ib Study to Evaluate the Safety and Pharmacokinetics of MOR103, a Human Antibody to GM-CSF, in Patients With Multiple Sclerosis
Multiple sclerosis (MS) is a chronic inflammatory disease associated with central nervous system (CNS) demyelination and subsequent axonal degeneration. Multiple sclerosis exhibits an unpredictable and variable clinical course.
Multiple sclerosis plaques contain numerous types of cells and infiltrating macrophages have been identified to contribute significantly to demyelination in both clinical MS and animal models of MS. Granulocyte-macrophage colony-stimulating factor (GM CSF) stimulates proliferation and activation of macrophages, monocytes, neutrophils, eosinophils, dendritic cells and microglia with subsequent induction of proinflammatory biomolecules.
Therefore blocking GM CSF activity might be a therapeutic approach for the treatment of MS.
Read the detailed description
Recent clinical studies demonstrated a possible dysregulation of the balance of pro and anti inflammatory lymphocytes, which may contribute to the pathogenesis of MS.
It was shown in animal models of EAE that during the disease effect or phase GM CSF sustained neuroinflammation via myeloid cells that infiltrate the CNS proving an essential role of GM CSF in encephalitogenicity.
- Conditions
- Multiple Sclerosis
- Being tested
- MOR103, Placebo
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MOR103Biological
Anti-GM-CSF monoclonal antibody
PlaceboOther
Placebo to anti-GM-CSF monoclonal antibody
| Study group | Role | What they receive |
|---|---|---|
| MOR103 0.5 mg/kg | Experimental | 6 doses of MOR103 0.5 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). Receives: Biological: MOR103 |
| MOR103 1.0 mg/kg | Experimental | 6 doses of MOR103 1.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). Receives: Biological: MOR103 |
| MOR103 2.0 mg/kg | Experimental | 6 doses of MOR103 2.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). Receives: Biological: MOR103 |
| Placebo | Placebo comparator | 6 doses of placebo administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)
The safety of multiple doses of MOR103 in patients with relapsing-remitting or secondary progressive multiple sclerosis (MS) was assessed by evaluation of the incidence of TEAEs and TESAEs. A full listing of adverse events recorded during this trial can be found in the Adverse Events section. AEs were regarded as treatment emergent if they started on or after the first date of study drug administration or if they were present prior to the first date of study drug administration and increased in severity or relationship to study drug during the study. AEs were coded using MedDRA version 16.1
Measured: From the first dose (week 0) to study endpoint (week 20)
Secondary outcomes (7)
Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples
To assess the potential immunogenicity of MOR103, a central bioanalytical laboratory (Eurofins Medinet BV, Breda, The Netherlands) tested serum samples obtained at baseline and at 3 post-treatment time points (week 14, week 16, and week 20/end of study) for anti-MOR103 antibodies.
Measured: Baseline, week 14, week 16, and week 20/end of study
Mean Serum Concentration of MOR103 Over Time
MOR103 serum levels were measured at each visit. At all visits during the dosing period (weeks 0, 2, 6, 8, and 10), serum samples were taken before MOR103 administration (pre-dose) and 1 hour after the dose. In addition, at week 0 (first dose) and week 10 (last dose), additional samples were obtained at 2 hours and 4 hours after MOR103 administration. At visits that followed the dosing period (weeks 12, 14, 16, and 20), a single serum sample was obtained at any time during the visit.
Measured: Week 0 (dose 1) to week 20 (end of study)
Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses
At the week 0 (first dose) and week 10 (last dose) visits, serum samples were obtained at pre-dose and at 1, 2, and 4 hours after the dose. Cmax values for each patient were calculated based on these data, and the mean Cmax values for the dose cohort are presented here. Because Cmax refers to the maximum serum concentration, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable, as they represent the concentration of MOR103, but not the Cmax.
Measured: Week 0 (first dose) and week 10 (last dose)
Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses
At the week 0 (first dose) and week 10 (last dose) visits, serum samples were obtained at pre-dose and at 1, 2, and 4 hours after the dose. Tmax values for each patient were calculated based on these data, and the mean Tmax values for the dose cohort are presented here. Because Tmax refers to the time to maximum serum concentration, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable.
Measured: Week 0 (first dose) and week 10 (last dose)
Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC
At week 0 (first dose) and week 10 (last dose), serum samples were obtained at pre-dose and at 1, 2, 4, and 336 hours after start of dosing. To calculate the accumulation ratio, the apparent AUC calculated for the last dose was divided by the apparent AUC following the first dose using the described time points for each dosing. Because AUC is a summary outcome, only one value is presented for each dose cohort on each day; values at each PK time point are not applicable.
Measured: Week 0 (first dose) and week 10 (last dose)
Number of New T1 Gadolinium-enhancing Lesions
Magnetic resonance imaging (MRI) tests were performed at screening (to confirm subject eligibility) and at Weeks 4, 8, 2, and 16. MRIs at post-screening time points were used to assess the number of new lesions as revealed by gadolinium (Gd) enhancement. Gd-enhanced MRIs reveal new brain lesions reflecting areas of active inflammation. MRI images were assessed centrally by Synarc A/S (Hamburg, Germany).
Measured: Week 4, week 8, week 12, and week 16.
Number of New or Enlarging T2 Lesions
T2-weighted magnetic resonance imaging (MRI) tests were performed at Weeks 8, 12, and 16 to assess the number of new or enlarging T2 brain lesions, a sign of MS activity. MRI images were assessed centrally by Synarc A/S (Hamburg, Germany).
Measured: Week 8, week 12, and week 16.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startJan 2012
- Primary completionJan 2014
- Study completionFeb 2014
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- MorphoSys AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Roman P Korolkiewicz, MD, PhD, Study director, MorphoSys AG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517282
- Sponsor's protocol ID
- 2011-001064-22
- Status last verified
- Nov 2014
- First submitted
- 10 Jan 2012
- Last updated
- 21 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Phase Ib Study to Evaluate the Safety and Pharmacokinetics of MOR103, a Human Antibody to GM-CSF, in Patients With Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01517282
- Acronym / sponsor ID
- 2011-001064-22
- Conditions
- Multiple Sclerosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- MorphoSys AGIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Jan 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 25 Jan 2012 (estimated)
- Results
- Posted 13 Oct 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Multiple sclerosis (MS) is a chronic inflammatory disease associated with central nervous system (CNS) demyelination and subsequent axonal degeneration. Multiple sclerosis exhibits an unpredictable and variable clinical course.
Multiple sclerosis plaques contain numerous types of cells and infiltrating macrophages have been identified to contribute significantly to demyelination in both clinical MS and animal models of MS. Granulocyte-macrophage colony-stimulating factor (GM CSF) stimulates proliferation and activation of macrophages, monocytes, neutrophils, eosinophils, dendritic cells and microglia with subsequent induction of proinflammatory biomolecules.
Therefore blocking GM CSF activity might be a therapeutic approach for the treatment of MS.
Detailed description
Recent clinical studies demonstrated a possible dysregulation of the balance of pro and anti inflammatory lymphocytes, which may contribute to the pathogenesis of MS.
It was shown in animal models of EAE that during the disease effect or phase GM CSF sustained neuroinflammation via myeloid cells that infiltrate the CNS proving an essential role of GM CSF in encephalitogenicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MOR103 0.5 mg/kg | Experimental | Biological: MOR1036 doses of MOR103 0.5 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). |
| MOR103 1.0 mg/kg | Experimental | Biological: MOR1036 doses of MOR103 1.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). |
| MOR103 2.0 mg/kg | Experimental | Biological: MOR1036 doses of MOR103 2.0 mg/kg administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). |
| Placebo | Placebo comparator | Other: Placebo6 doses of placebo administered on Days 1 (Baseline), 15 (Visit 2), 29 (Visit 3), 43 (Visit 4), 57 (Visit 5), and 71 (Visit 6). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Outpatients with a diagnosis of RRMS or SPMS, who are currently not being treated and who have at least 1 of the following:
- At least 1 documented relapse within 1 year before Screening, or
- Two documented relapses within the past 2 years before Screening, or
- A new gadolinium (Gd)-enhancing lesion on magnetic resonance imaging (MRI) T1-weighted imaging within 1 year before Screening, or
- A new T2 lesion on MRI within 1 year before Screening. The patient must have 10 or less, Gd-enhancing lesions per T1-weighted MRI at Screening as assessed by a central reader.
Key exclusion criteria (12 listed)
- A patient with primary progressive MS (PPMS)
- A patient who has previously received at any time any of the following
- A patient who has not stabilized, in the opinion of the investigator
- A patient with any medical condition or uncontrolled disease states other than MS requiring or likely to require systemic treatment with corticosteroids or other immune compromising agents
- A patient with current or a history of major chronic inflammatory autoimmune diseases other than MS
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 |
|---|---|---|
| MOR103Anti-GM-CSF monoclonal antibody | Biological | MOR103 0.5 mg/kg, MOR103 1.0 mg/kg, MOR103 2.0 mg/kg |
| PlaceboPlacebo to anti-GM-CSF monoclonal antibody | Other | Placebo |
Primary outcome
Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From the first dose (week 0) to study endpoint (week 20)
The safety of multiple doses of MOR103 in patients with relapsing-remitting or secondary progressive multiple sclerosis (MS) was assessed by evaluation of the incidence of TEAEs and TESAEs. A full listing of adverse events recorded during this trial can be found in the Adverse Events section. AEs were regarded as treatment emergent if they started on or after the first date of study drug administration or if they were present prior to the first date of study drug administration and increased in severity or relationship to study drug during the study. AEs were coded using MedDRA version 16.1
7 secondary outcomes
Percentages of Patients Negative for Anti-MOR103 Antibodies in Serum Samples
Time frame: Baseline, week 14, week 16, and week 20/end of study
Mean Serum Concentration of MOR103 Over Time
Time frame: Week 0 (dose 1) to week 20 (end of study)
Mean Maximum MOR103 Concentration (Cmax) After the First and Last MOR103 Doses
Time frame: Week 0 (first dose) and week 10 (last dose)
Mean Time to Maximum MOR103 Concentration (Tmax) After the First and Last MOR103 Doses
Time frame: Week 0 (first dose) and week 10 (last dose)
Accumulation Ratio for Area Under the MOR103 Serum Concentration Versus Time Curve (AUC) Over One Dosing Interval: Ratio of Week 10 (Last Dose) AUC to Week 0 (First Dose) AUC
Time frame: Week 0 (first dose) and week 10 (last dose)
Number of New T1 Gadolinium-enhancing Lesions
Time frame: Week 4, week 8, week 12, and week 16.
Number of New or Enlarging T2 Lesions
Time frame: Week 8, week 12, and week 16.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2014.
- 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.
Roman P Korolkiewicz, MD, PhD study director
MorphoSys AG
5 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MOR103 in people with Multiple Sclerosis, run by MorphoSys AG at 5 sites in 3 countries.
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 6 inclusion and 12 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 21 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Poland, United Kingdom, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 13 Oct 2014). 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?
Percentages of Patients With Treatment-emergent Adverse Events (TEAEs) or Treatment-emergent Serious Adverse Events (TESAEs) (time frame: From the first dose (week 0) to study endpoint (week 20)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Nov 2014.