Multiple SclerosisPhase 1/2NCT01212094
Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe)
A Phase 1/2 study testing Rituximab and normal saline in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Secondary-progressive multiple sclerosis (SP-MS) is the chronic phase of multiple sclerosis (MS). The majority of people who have relapsing-remitting MS eventually develop SP-MS. There are currently no effective treatments for SP-MS. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Rituximab and normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Dec 2015
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MS as defined by the modified McDonald s criteria (Polman, Reingold et al. 2005)
- SP-MS as documented by lack of MS relapse for the past 1 year and non-remitting/sustained (> 3 months) progression of disability
- Age 18-65, inclusive, at the time of the first screening baseline visit
- EDSS 3.0 to 7.0, inclusive, at the time of the first screening baseline visit
- Able to provide informed consent
- Willing to participate in all aspects of trial design and follow-up
Show all 10Show fewer
- Lack of CEL on all MRIs performed within the last 12 months or if patient has CEL, then documentation that they tried and failed or could not tolerate FDA approved disease modifying therapies (DMTh)
- Not receiving any DMTh (such as IFN-beta preparation, glatiramer acetate, corticosteroid, natalizumab, fingolimod, immunosuppressive agents or experimental therapeutics) for a period of at least 1 month before enrollment in the study, allowing for at least a 1-year
- period off therapy prior to the first study dose
- Agreeing to commit to the use of a reliable/accepted method of birth control (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom with spermicide) or they have undergone surgical sterilization (such as hysterectomy, tubal ligation, or vasectomy)) during enrollment in the study and through 12 months after the last dose of study drug
Who cannot join
- RR-MS or PP-MS
- Evidence of clearly documented MS relapse within the last 1 year
- Alternative diagnoses that can explain neurological disability and MRI findings
- Clinically significant medical disorders that, in the judgment of the investigators could cause CNS tissue damage, limit its repair, expose the patient to undue risk of harm or prevent the patient from completing the study (such as, but not limited to cerebrovascular disease, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative disorder)
- Pregnant or breastfeeding female
- History or sign of congenital or acquired immunodeficiency or chronic infections, such as HIV/AIDS, Hepatitis A, B or C, HTLV-1 carrier and others that would expose patient to risks of pathogen reactivation associated with rituximab treatment
Show all 15Show fewer
- Abnormal screening/baseline blood tests exceeding any of the limits defined below:
- Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values.
- Total white blood cell count < 3 000/mm(3)
- Platelet count < 85 000/mm(3)
- Serum creatinine level > 2.0 mg/dl and eGFR (glomerular filtration rate) < 60
- Serological evidence of HIV, HTLV-1 or active hepatitis A, B or C
- Positive pregnancy test
- Positive CSF or serum quantitative PCR for JC virus on CSF collected from the baseline spinal tap (test will be performed by CLIA certified laboratory of Gene Major, NINDS)
- Total serum IgG < 600mg/dl (nl 642-1730mg/dl) or total serum IgM < 30mg/dl (nl 34-342mg/dl) as these Ig deficiencies would suggest underlying abnormalities with B cell function/maturation
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Background:
- Secondary-progressive multiple sclerosis (SP-MS) is the chronic phase of multiple sclerosis (MS). The majority of people who have relapsing-remitting MS eventually develop SP-MS. There are currently no effective treatments for SP-MS. Researchers are interested in determining whether the drug rituximab, which is used to treat rheumatoid arthritis and some types of cancer, is able to target certain white blood cells that are thought to play a role in the progression of SP-MS. To ensure that the rituximab will reach the brain and spinal cord, participants will receive it by intravenous drip and by intrathecal injection (through a lumbar puncture into the cerebrospinal fluid).
Read more
Objectives:
- To evaluate the safety and effectiveness of combined intravenous and intrathecal rituximab in individuals with secondary-progressive multiple sclerosis.
Eligibility:
- Individuals between 18 and 65 years of age who have been diagnosed with SP-MS and have been off any form of immunosuppressive therapy for at least 3 months.
Design:
- The study will involve a 1-year pretreatment baseline series of visits, followed by a 2-year treatment period. Participants will provide blood samples throughout treatment as directed by the study researchers, and additional studies may be performed during the study period if participants consent to further investigation.
Read the detailed description
Objective: The primary goal of this study is to define the safety and efficacy of combined systemic and intrathecal (IT) B cell-depleting therapy (i.e. anti-CD20, rituximab) in patients with secondary-progressive multiple sclerosis (SP-MS). The secondary goals of this study are to collect longitudinal data to help identify the most sensitive outcome measures and trial design for future Phase II trials for SP-MS patients and to investigate the mechanism of action of rituximab on the human immune system.
Study Population: Patients with SP-MS and mild to moderate level of clinical disability, who have no medical contraindication to IT or intravenous (IV) administration of rituximab.
Design: This is double blind, placebo-controlled, single center, baseline versus treatment, Phase I/II clinical trial of IV and IT rituximab in SP-MS patients.
Outcome Measures: Quantitative neuroimaging measures of central nervous system (CNS: i.e. brain and spinal cord) tissue destruction and clinical and functional (i.e. electrophysiological) measures of neurological disability will be collected every 6-12 months. Additionally, biomarkers focusing on analysis of cerebral spinal fluid (CSF) B cells and immunological responses to EBV will be collected at baseline and during treatment. The trial is currently powered using progression of brain atrophy as detected by SIENA methodology as the primary outcome measure. However, this may not be the most sensitive outcome available. In recognition of this, the trial has an adaptive design: it incorporates analysis of the progression of CNS tissue destruction, as measured by quantitative MRI markers, and clinical/paraclinical markers, defined as secondary outcome measures, in the first 30 enrolled patients during the year long pre-treatment baseline prior to randomization. All defined outcome measures collected in the first 30 enrolled patients will be transformed into z-scores and compared for the robustness of longitudinal change over the coefficient of variation. As a result, the primary outcome measure of this trial will be the comparison of individualized rates of brain atrophy progression between the rituximab and placebo groups after 2 years of treatment; unless the predetermined analysis establishes that one of the secondary outcome measures has a higher z-score than the brain atrophy measurement. In this case, the primary outcome would be the efficacy of rituximab versus placebo in inhibiting patient-specific slopes of functional or structural deterioration as measured by this more sensitive biomarker of CNS tissue destruction.
Trial also included interim analysis for the efficacy of B cell depletion from the intrathecal compartment with pre-defined stopping criteria for futility: if less than 50% of intrathecal B cells were depleted by active treatment (measured by <25% decrease in CSF CXCL13 and <50% increase in CSF BAFF), then trial was deemed to be underpowered to demonstrate efficacy on clinical or MRI outcomes and would be stopped.
- Conditions
- Multiple Sclerosis
- Being tested
- Rituximab, normal saline
- Keywords
- Rituximab, Multiple Sclerosis, Intrathecal, MS, Secondary-Progressive Multiple Sclerosis, SP-MS
- Medical subject headings
- Multiple Sclerosis, Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituximabDrug
normal salineOther
Also called saline
normal saline
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Patients received 25mg of rituximab into the CSF and 200mg of rituximab intravenously at Month 0, followed by additional 200mg of rituximab intravenously at Month 0.5 and another 25mg of rituximab into CSF at months 1.5 and 12. Receives: Drug: Rituximab |
| Placebo | Placebo comparator | Patients received normal saline into the CSF and intravenously at Month 0, followed by additional normal saline intravenously at Month 0.5 and another dose of normal saline into CSF at months 1.5 and 12. Receives: Other: normal saline |
| Baseline | No intervention | Patients in their first year baseline prior to study drug phase |
What is being measured
The primary outcome is the main question the study is designed to answer.
Analysis of Changes in CSF CXCL13 Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration
This outcome is for interim analysis of the efficacy of B cell depletion from the CSF 3 months after giving rituximab or placebo into the cerebrospinal fluid (CSF). It compares concentration of chemokine CXCL13 before and 3 months after administration of drug into the CSF. We averaged two time-points before treatment (CSF collected 1 year apart, at month -12 and month 0) and compared it to the single time-point (month 3), which was 3 months from the initiation of drug dosing. CXCL13 is released by activated B cells, T cells and by follicular dendritic cells and has been linked previously with MS inflammation in the brain and spinal cord. The protocol-stipulated threshold for trial continuation was at least 25% decrease in CSF CXCL13 induced by active treatment with significance level p=0.025.
Measured: 3 months
Analysis of Changes in CSF BAFF Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration
This outcome is for interim analysis of the efficacy of B cell depletion from the CSF 3 months after giving rituximab or placebo into the cerebrospinal fluid (CSF). It compares concentration of B-cell activating factor (BAFF) before and 3 months after administration of drug into the CSF. We averaged two time-points before treatment (CSF collected 1 year apart, at month -12 and month 0) and compared it to the single time-point (month 3), which was 3 months from the initiation of drug dosing. BAFF is consumed by B cells, therefore effective B cell depletion increases levels of BAFF. The protocol-stipulated threshold for trial continuation was at least 50% increase in CSF BAFF induced by active treatment with significance level p=0.025.
Measured: 3 months
Secondary outcomes (11)
Analysis of Changes in CSF B Cell Numbers Between Rituximab and Placebo
This outcome is for interim analysis of the efficacy of B cell depletion from the CSF 3 months after giving rituximab or placebo into the cerebrospinal fluid (CSF). It compares absolute numbers of CSF B cells calculated as proportion of B cells (identified from flow cytometry data) in all immune cells measured in 50-fold concentrated CSF. We averaged two time-points before treatment (CSF collected 1 year apart, at month -12 and month 0) and compared it to the single time-point (month 3), which was 3 months from the initiation of drug dosing.
Measured: 3 months
Expanded Disability Status Scale (EDSS)
Trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes was not performed. EDSS is a clinical rating scale for disability ranging from 0 (normal neurological exam) to 10 (death due to MS) in half point increments.
Measured: 24 months
Scripps Neurological Rating Scale (NRS)
NRS is a quantitative assessment based on 22 parameters of the neurological exam with scores ranging from maximum of 100 (normal neurological exam) to a minimum of -10 (death due to MS). The higher the score, the better the patient's level of function.
trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes makes no sense
Measured: 24 months
Timed 25 Foot Walk
Measure of mobility and leg function based on a timed 25 foot walk. Patient is directed to walk as quickly as possible, with or without an assitive device, to one end of a 25foot course and this is repeated for a total of 2 times. The score is the average of the two completed trials.
Trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes makes no sense
Measured: 24 months
9-Hole Peg Test
Measure of upper extremity (arm and hand) function where patients are asked to pick up one peg at a time, using one hand only, and putting them into the holes as quickly as possible until all the holes are filled and then removing them one at a time as quickly as possible. The dominant and non-dominant hands are tested twice. The time limit per trial is 5 minutes.
Trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes makes no sense
Measured: 24 months
Multiple Sclerosis Functional Composite (MSFC)
The MSFC is a three-part standardized assessment tool that measures arm, leg, and cognitive function. The scoring is based on the average Z-score for all three parts of the the assessment.
Measured: 24 months
EDSS
Trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes was not performed. EDSS is a clinical rating scale for disability ranging from 0 (normal neurological exam) to 10 (death due to MS) in half point increments.
Measured: 0 months
Scripps Neurological Rating Scale (NRS)
NRS is a quantitative assessment based on 22 parameters of the neurological exam with scores ranging from maximum of 100 (normal neurological exam) to a minimum of -10 (death due to MS). The higher the score, the better the patient's level of function.
trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes makes no sense
Measured: 0 Months
Timed 25 Foot Walk
Measure of mobility and leg function based on a timed 25 foot walk. Patient is directed to walk as quickly as possible, with or without an assitive device, to one end of a 25foot course and this is repeated for a total of 2 times. The score is the average of the two completed trials.
Trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes makes no sense
Measured: 0 months
9-Hole Peg Test
Measure of upper extremity (arm and hand) function where patients are asked to pick up one peg at a time, using one hand only, and putting them into the holes as quickly as possible until all the holes are filled and then removing them one at a time as quickly as possible. The dominant and non-dominant hands are tested twice. The time limit per trial is 5 minutes.
Trial was closed prematurely and therefore formal statistical analysis of the acquired clinical outcomes makes no sense
Measured: 0 months
Multiple Sclerosis Functional Composite (MSFC)
The MSFC is a three-part standardized assessment tool that measures arm, leg, and cognitive function. The scoring is based on the average Z-score for all three parts of the the assessment.
Measured: 0 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionDec 2015
- Study completionDec 2015
Why it stopped: The efficacy on CSF biomarkers failed to reach criteria for continuation of the trial
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Bibiana Bielekova, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01212094
- Sponsor's protocol ID
- 100212
- Other IDs
- 10-N-0212
- Status last verified
- Mar 2016
- First submitted
- 29 Sep 2010
- Last updated
- 28 Mar 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
- Expanded access
- Available
Publications
Kosa P, Komori M, Waters R, Wu T, Cortese I, Ohayon J, Fenton K, Cherup J, Gedeon T, Bielekova B. Novel composite MRI scale correlates highly with disability in multiple sclerosis patients. Mult Scler Relat Disord. 2015 Nov;4(6):526-35. doi: 10.1016/j.msard.2015.08.009. Epub 2015 Aug 28.
PubMed 26590659Kosa P, Ghazali D, Tanigawa M, Barbour C, Cortese I, Kelley W, Snyder B, Ohayon J, Fenton K, Lehky T, Wu T, Greenwood M, Nair G, Bielekova B. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment. Front Neurol. 2016 Aug 15;7:131. doi: 10.3389/fneur.2016.00131. eCollection 2016.
PubMed 27574516
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double Blind Combination of Rituximab by Intravenous and Intrathecal Injection Versus Placebo in Patients With Low-Inflammatory Secondary Progressive Multiple Sclerosis (RIVITaLISe)
- ClinicalTrials.gov ID
- NCT01212094
- Acronym / sponsor ID
- 100212
- Conditions
- Multiple Sclerosis
- Keywords
- Rituximab, Multiple Sclerosis, Intrathecal, MS, Secondary-Progressive Multiple Sclerosis, SP-MS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The efficacy on CSF biomarkers failed to reach criteria for continuation of the trial
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Sep 2010
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 30 Sep 2010 (estimated)
- Results
- Posted 28 Mar 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Secondary-progressive multiple sclerosis (SP-MS) is the chronic phase of multiple sclerosis (MS). The majority of people who have relapsing-remitting MS eventually develop SP-MS. There are currently no effective treatments for SP-MS. Researchers are interested in determining whether the drug rituximab, which is used to treat rheumatoid arthritis and some types of cancer, is able to target certain white blood cells that are thought to play a role in the progression of SP-MS. To ensure that the rituximab will reach the brain and spinal cord, participants will receive it by intravenous drip and by intrathecal injection (through a lumbar puncture into the cerebrospinal fluid).
Objectives:
- To evaluate the safety and effectiveness of combined intravenous and intrathecal rituximab in individuals with secondary-progressive multiple sclerosis.
Eligibility:
- Individuals between 18 and 65 years of age who have been diagnosed with SP-MS and have been off any form of immunosuppressive therapy for at least 3 months.
Design:
- The study will involve a 1-year pretreatment baseline series of visits, followed by a 2-year treatment period. Participants will provide blood samples throughout treatment as directed by the study researchers, and additional studies may be performed during the study period if participants consent to further investigation.
Detailed description
Objective: The primary goal of this study is to define the safety and efficacy of combined systemic and intrathecal (IT) B cell-depleting therapy (i.e. anti-CD20, rituximab) in patients with secondary-progressive multiple sclerosis (SP-MS). The secondary goals of this study are to collect longitudinal data to help identify the most sensitive outcome measures and trial design for future Phase II trials for SP-MS patients and to investigate the mechanism of action of rituximab on the human immune system.
Study Population: Patients with SP-MS and mild to moderate level of clinical disability, who have no medical contraindication to IT or intravenous (IV) administration of rituximab.
Design: This is double blind, placebo-controlled, single center, baseline versus treatment, Phase I/II clinical trial of IV and IT rituximab in SP-MS patients.
Outcome Measures: Quantitative neuroimaging measures of central nervous system (CNS: i.e. brain and spinal cord) tissue destruction and clinical and functional (i.e. electrophysiological) measures of neurological disability will be collected every 6-12 months. Additionally, biomarkers focusing on analysis of cerebral spinal fluid (CSF) B cells and immunological responses to EBV will be collected at baseline and during treatment. The trial is currently powered using progression of brain atrophy as detected by SIENA methodology as the primary outcome measure. However, this may not be the most sensitive outcome available. In recognition of this, the trial has an adaptive design: it incorporates analysis of the progression of CNS tissue destruction, as measured by quantitative MRI markers, and clinical/paraclinical markers, defined as secondary outcome measures, in the first 30 enrolled patients during the year long pre-treatment baseline prior to randomization. All defined outcome measures collected in the first 30 enrolled patients will be transformed into z-scores and compared for the robustness of longitudinal change over the coefficient of variation. As a result, the primary outcome measure of this trial will be the comparison of individualized rates of brain atrophy progression between the rituximab and placebo groups after 2 years of treatment; unless the predetermined analysis establishes that one of the secondary outcome measures has a higher z-score than the brain atrophy measurement. In this case, the primary outcome would be the efficacy of rituximab versus placebo in inhibiting patient-specific slopes of functional or structural deterioration as measured by this more sensitive biomarker of CNS tissue destruction.
Trial also included interim analysis for the efficacy of B cell depletion from the intrathecal compartment with pre-defined stopping criteria for futility: if less than 50% of intrathecal B cells were depleted by active treatment (measured by <25% decrease in CSF CXCL13 and <50% increase in CSF BAFF), then trial was deemed to be underpowered to demonstrate efficacy on clinical or MRI outcomes and would be stopped.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: RituximabPatients received 25mg of rituximab into the CSF and 200mg of rituximab intravenously at Month 0, followed by additional 200mg of rituximab intravenously at Month 0.5 and another 25mg of rituximab into CSF at months 1.5 and 12. |
| Placebo | Placebo comparator | Other: normal salinePatients received normal saline into the CSF and intravenously at Month 0, followed by additional normal saline intravenously at Month 0.5 and another dose of normal saline into CSF at months 1.5 and 12. |
| Baseline | No intervention | –Patients in their first year baseline prior to study drug phase |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- MS as defined by the modified McDonald s criteria (Polman, Reingold et al. 2005)
- SP-MS as documented by lack of MS relapse for the past 1 year and non-remitting/sustained (> 3 months) progression of disability
- Age 18-65, inclusive, at the time of the first screening baseline visit
- EDSS 3.0 to 7.0, inclusive, at the time of the first screening baseline visit
- Able to provide informed consent
Key exclusion criteria (15 listed)
- RR-MS or PP-MS
- Evidence of clearly documented MS relapse within the last 1 year
- Alternative diagnoses that can explain neurological disability and MRI findings
- Clinically significant medical disorders that, in the judgment of the investigators could cause CNS tissue damage, limit its repair, expose the patient to undue risk of harm or prevent the patient from completing the study (such as, but not limited to cerebrovascular disease, ischemic cardiomyopathy, clotting disorder, brittle diabetes, neurodegenerative disorder)
- Pregnant or breastfeeding female
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 |
|---|---|---|
| Rituximab | Drug | Rituximab |
| normal salineAlso: salinenormal saline | Other | Placebo |
Primary outcome
Analysis of Changes in CSF CXCL13 Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration
Time frame: 3 months
This outcome is for interim analysis of the efficacy of B cell depletion from the CSF 3 months after giving rituximab or placebo into the cerebrospinal fluid (CSF). It compares concentration of chemokine CXCL13 before and 3 months after administration of drug into the CSF. We averaged two time-points before treatment (CSF collected 1 year apart, at month -12 and month 0) and compared it to the single time-point (month 3), which was 3 months from the initiation of drug dosing. CXCL13 is released by activated B cells, T cells and by follicular dendritic cells and has been linked previously with MS inflammation in the brain and spinal cord. The protocol-stipulated threshold for trial continuation was at least 25% decrease in CSF CXCL13 induced by active treatment with significance level p=0.025.
Analysis of Changes in CSF BAFF Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration
Time frame: 3 months
This outcome is for interim analysis of the efficacy of B cell depletion from the CSF 3 months after giving rituximab or placebo into the cerebrospinal fluid (CSF). It compares concentration of B-cell activating factor (BAFF) before and 3 months after administration of drug into the CSF. We averaged two time-points before treatment (CSF collected 1 year apart, at month -12 and month 0) and compared it to the single time-point (month 3), which was 3 months from the initiation of drug dosing. BAFF is consumed by B cells, therefore effective B cell depletion increases levels of BAFF. The protocol-stipulated threshold for trial continuation was at least 50% increase in CSF BAFF induced by active treatment with significance level p=0.025.
11 secondary outcomes
Analysis of Changes in CSF B Cell Numbers Between Rituximab and Placebo
Time frame: 3 months
Expanded Disability Status Scale (EDSS)
Time frame: 24 months
Scripps Neurological Rating Scale (NRS)
Time frame: 24 months
Timed 25 Foot Walk
Time frame: 24 months
9-Hole Peg Test
Time frame: 24 months
Multiple Sclerosis Functional Composite (MSFC)
Time frame: 24 months
EDSS
Time frame: 0 months
Scripps Neurological Rating Scale (NRS)
Time frame: 0 Months
Timed 25 Foot Walk
Time frame: 0 months
9-Hole Peg Test
Time frame: 0 months
Multiple Sclerosis Functional Composite (MSFC)
Time frame: 0 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26590659Kosa P, Komori M, Waters R, Wu T, Cortese I, Ohayon J, Fenton K, Cherup J, Gedeon T, Bielekova B. Novel composite MRI scale correlates highly with disability in multiple sclerosis patients. Mult Scler Relat Disord. 2015 Nov;4(6):526-35. doi: 10.1016/j.msard.2015.08.009. Epub 2015 Aug 28.
- Derived from this study: PubMed 27574516Kosa P, Ghazali D, Tanigawa M, Barbour C, Cortese I, Kelley W, Snyder B, Ohayon J, Fenton K, Lehky T, Wu T, Greenwood M, Nair G, Bielekova B. Development of a Sensitive Outcome for Economical Drug Screening for Progressive Multiple Sclerosis Treatment. Front Neurol. 2016 Aug 15;7:131. doi: 10.3389/fneur.2016.00131. eCollection 2016.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Bibiana Bielekova, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Rituximab and normal saline in people with Multiple Sclerosis, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 10 inclusion and 15 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: stopped early, as of the sponsor's last update on 28 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 28 Mar 2016). 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?
Analysis of Changes in CSF CXCL13 Induced by Active Treatment (Rituximab) Measured 3 Months After 1st Drug Administration (time frame: 3 months). The study lists 2 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 NCT01212094, which also lists 2 linked publications.
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 28 Mar 2016.