Relapsing Multiple SclerosisPhase 2NCT03249714
Efficacy and Safety of Ofatumumab Compared to Placebo in Patients With Relapsing Multiple Sclerosis Followed by Extended Treatment With Open-label Ofatumumab
A Phase 2 study testing Ofatumumab in people with Relapsing Multiple Sclerosis, run by Novartis Pharmaceuticals at 14 sites in 2 countries.
Trial summary
The study provided efficacy, safety, and pharmacokinetics (PK) data for patients with relapsing multiple sclerosis (RMS) in Japan and the other countries Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Relapsing Multiple Sclerosis
- What is being tested?
- Ofatumumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 64 participants
- Where
- 14 sitesin 2 countries
- Study dates
- 15 Mar 2018to 29 Jul 2020
- 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
- Diagnosis of multiple sclerosis (MS)
- Relapsing MS (RMS)
- At least 1 appearance of a new neurological abnormality or worsening of pre-existing neurological abnormality during the previous 2 years prior to Screening AND an MRI activity (Gd-enhancing T1 lesions or new or enlarging T2 lesions) in brain during the previous 1 year prior to randomization
- EDSS score of 0 to 5.5
Who cannot join
- Primary progressive MS or SPMS without disease activity
- Patients with an active chronic disease of the immune system other than MS
- Patients at risk of developing or having reactivation of hepatitis
- Patients with active systemic infections or with neurological findings consistent with PML
Trial locations and contacts
14 sites in 2 countries.
14 sites in 2 countries
Japan12 sites
Novartis Investigative Site
Chiba, 260 8677
Novartis Investigative Site
Fukuoka, Fukuoka, 812-8582
Novartis Investigative Site
Kawagoe, Saitama, 350 8550
Novartis Investigative Site
Kodaira, Tokyo, 187-8551
Novartis Investigative Site
Morioka, Iwate, 020-8505
Novartis Investigative Site
Niigata, 951 8520
Novartis Investigative Site
Osaka, 556-0016
Novartis Investigative Site
Sapporo, Hokkaido, 063-0005
Novartis Investigative Site
Sendai, Miyagi, 980 8574
Novartis Investigative Site
Sendai, Miyagi, 983 8512
Novartis Investigative Site
Shinjuku-ku, Tokyo, 160 8582
Novartis Investigative Site
Tōon, Ehime, 791-0295
Russia2 sites
Novartis Investigative Site
Kazan', 420021
Novartis Investigative Site
Novosibirsk, 630007
About this study
Official title: A 24-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Ofatumumab in Patients With Relapsing Multiple Sclerosis Followed by an Extended Treatment of at Least 24 Weeks With Open-label Ofatumumab
The study provided efficacy, safety, and pharmacokinetics (PK) data for patients with relapsing multiple sclerosis (RMS) in Japan and the other countries
Read the detailed description
This study had 2 parts: A controlled Core and an open-label Extension.
- Core part: A 24-week, randomized, double-blind, placebo controlled, parallel-group, multicenter study evaluated the efficacy, safety and tolerability and PK of ofatumumab in patients with RMS.
- Extension part: The Core part was followed by an Extension part in which all patients received open-label ofatumumab. In the Extension part, patients were treated for at least 24 weeks and no longer than 48 weeks.
Sixty-four patients were randomized in a 2:1 ratio to ofatumumab or placebo in the Core part; half of the study patients were from Japan and the other half from the other countries.
- Conditions
- Relapsing Multiple Sclerosis
- Being tested
- Ofatumumab, Matching placebo of ofatumumab
- Keywords
- double-blind, placebo controlled, ofatumumab, relapsing multiple sclerosis, Japanese patients, MS, RMS, adult, OMB157
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OfatumumabDrug
Provided in pre-filled syringes for subcutaneous injection (s.c.) administration containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content)
Matching placebo of ofatumumabDrug
Matching placebo in pre-filled syringes
| Study group | Role | What they receive |
|---|---|---|
| OMB 20 mg | Experimental | Ofatumumab 20 mg subcutaneous injection on Days 1,7, 14 and every 4 weeks for 24 weeks in Core. Core placebo patients received loading dose at Weeks 25 and 26 and then all Extension patients received dose every 4 Weeks up to Week 48. Receives: Drug: Ofatumumab |
| Placebo | Placebo comparator | Placebo subcutaneous injection matching to ofatumumab every 4 weeks for 24 weeks in Core Receives: Drug: Matching placebo of ofatumumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part
Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, and subgroup of baseline number of Gd-enhancing T1 lesions (0 or >=1) as explanatory variables, and logarithm of the patient's number of scans as the offset variable.
Measured: Baseline up to Week 24
Secondary outcomes (11)
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part
Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, subgroup of baseline number of Gd-enhancing T1 lesions (0 or >=1), and the treatment-by-region interaction term as explanatory variables, and the patient's number of scans as the offset variable.
Measured: Baseline up to Week 24
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part
Number of new/enlarging T2 lesions on the last available MRI scan in the Core Part (up to Week 24) relative to baseline, adjusted for different follow-up times. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log-link. The model included each patient's last available number of new or enlarging T2 lesions relative to baseline as the response variable, and treatment, region, subgroup of baseline number of Gd-enhancing T1 lesions (0 or >=1), and baseline volume of T2 lesions as explanatory variables, and the patient's follow-up time as the offset variable.
Measured: Baseline up to Week 24
Annualized Relapse Rate (ARR) - Core Part
ARR was the number of confirmed MS relapses in a year. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). ARR was calculated as a rate for population, rather than at patient-level, using a negative binomial regression model with log-link. The model included each patient's number of confirmed relapses as the response variable, and treatment and region as explanatory variables, and the patient's follow-up time as the offset variable.
Measured: Baseline up to Week 24
Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part
Blood samples were collected at the scheduled visit. Summary statistics of PK concentrations from trough samples.
Measured: Pre-dose at Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
B-cell Counts - Japan vs Non-Japan - Core Part
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
Measured: Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part
Total number of Gd-enhancing T1 lesions per scan during the Extension Part (up to Week 48) calculated as a rate for population, rather than at patient-level. It was calculated as sum of each patient's total number of Gd-enhancing T1 lesions across scans at Week 36 and 48, divided by sum of each patient's total number of scans.
Measured: Week 24 up to Week 48
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part
Number of new/enlarging T2 lesions on the last available MRI scan in the Extension Part (up to Week 48) relative to Week 24, adjusted for different follow-up times. Annualized rate of new or enlarging T2 lesions was calculated by dividing the sum of each patient's number of new or enlarging T2 lesions relative to Week 24 by the sum of each patient's number of MRI assessment days during the Extension part, and then multiplying it by 365.25.
Measured: Week 24 up to Week 48
Annualized Relapse Rate (ARR) - Extension Part
ARR was the number of confirmed MS relapses in a year. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). ARR (time-based) was calculated by summing each patient's number of confirmed relapses observed during the Extension part, divided by the total number of each patient's days in a study of all patients during the Extension part, and multiplied by 365.25.
Measured: Week 24 up to Week 48
Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part
Blood samples were collected at the scheduled visits. Summary statistics of PK concentrations from trough samples.
Measured: Weeks 24, 28, 36, 48
B-cell Counts - Extension Part
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
Measured: Weeks 24, 36 and 48
Participants With Confirmed Relapse - Core and Extension Parts
A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system).
Measured: Baseline up to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2017
- Study start15 Mar 2018
- Primary completion26 Dec 2019
- Study completion29 Jul 2020
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 Relapsing Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe 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
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03249714
- Sponsor's protocol ID
- COMB157G1301
- Status last verified
- Apr 2022
- First submitted
- 11 Aug 2017
- Last updated
- 29 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24-week, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Ofatumumab in Patients With Relapsing Multiple Sclerosis Followed by an Extended Treatment of at Least 24 Weeks With Open-label Ofatumumab
- ClinicalTrials.gov ID
- NCT03249714
- Acronym / sponsor ID
- COMB157G1301
- Conditions
- Relapsing Multiple Sclerosis
- Keywords
- double-blind, placebo controlled, ofatumumab, relapsing multiple sclerosis, Japanese patients, MS, RMS, adult
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2018 (actual)
- Primary completion
- 26 Dec 2019 (actual)
- Study completion
- 29 Jul 2020 (actual)
- First posted
- 15 Aug 2017 (actual)
- Results
- Posted 18 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study provided efficacy, safety, and pharmacokinetics (PK) data for patients with relapsing multiple sclerosis (RMS) in Japan and the other countries
Detailed description
This study had 2 parts: A controlled Core and an open-label Extension.
- Core part: A 24-week, randomized, double-blind, placebo controlled, parallel-group, multicenter study evaluated the efficacy, safety and tolerability and PK of ofatumumab in patients with RMS.
- Extension part: The Core part was followed by an Extension part in which all patients received open-label ofatumumab. In the Extension part, patients were treated for at least 24 weeks and no longer than 48 weeks.
Sixty-four patients were randomized in a 2:1 ratio to ofatumumab or placebo in the Core part; half of the study patients were from Japan and the other half from the other countries.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OMB 20 mg | Experimental | Drug: OfatumumabOfatumumab 20 mg subcutaneous injection on Days 1,7, 14 and every 4 weeks for 24 weeks in Core. Core placebo patients received loading dose at Weeks 25 and 26 and then all Extension patients received dose every 4 Weeks up to Week 48. |
| Placebo | Placebo comparator | Drug: Matching placebo of ofatumumabPlacebo subcutaneous injection matching to ofatumumab every 4 weeks for 24 weeks in Core |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Diagnosis of multiple sclerosis (MS)
- Relapsing MS (RMS)
- At least 1 appearance of a new neurological abnormality or worsening of pre-existing neurological abnormality during the previous 2 years prior to Screening AND an MRI activity (Gd-enhancing T1 lesions or new or enlarging T2 lesions) in brain during the previous 1 year prior to randomization
- EDSS score of 0 to 5.5
Key exclusion criteria (4 listed)
- Primary progressive MS or SPMS without disease activity
- Patients with an active chronic disease of the immune system other than MS
- Patients at risk of developing or having reactivation of hepatitis
- Patients with active systemic infections or with neurological findings consistent with PML
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 |
|---|---|---|
| OfatumumabProvided in pre-filled syringes for subcutaneous injection (s.c.) administration containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content) | Drug | OMB 20 mg |
| Matching placebo of ofatumumabMatching placebo in pre-filled syringes | Drug | Placebo |
Primary outcome
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part
Time frame: Baseline up to Week 24
Total number of Gd-enhancing T1 lesions across scans at Week 12, 16, 20, and 24 were adjusted for the different numbers of scans. This was calculated as a rate for population, rather than at patient level, using a negative binomial regression model with log link. The model included each patient's total number of Gd-enhancing T1 lesions as the response variable, and treatment, region, and subgroup of baseline number of Gd-enhancing T1 lesions (0 or >=1) as explanatory variables, and logarithm of the patient's number of scans as the offset variable.
11 secondary outcomes
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part
Time frame: Baseline up to Week 24
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part
Time frame: Baseline up to Week 24
Annualized Relapse Rate (ARR) - Core Part
Time frame: Baseline up to Week 24
Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part
Time frame: Pre-dose at Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
B-cell Counts - Japan vs Non-Japan - Core Part
Time frame: Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part
Time frame: Week 24 up to Week 48
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part
Time frame: Week 24 up to Week 48
Annualized Relapse Rate (ARR) - Extension Part
Time frame: Week 24 up to Week 48
Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part
Time frame: Weeks 24, 28, 36, 48
B-cell Counts - Extension Part
Time frame: Weeks 24, 36 and 48
Participants With Confirmed Relapse - Core and Extension Parts
Time frame: Baseline up to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- A Plain Language Trial Summary is available on novctrd.comLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.
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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.
The record lists no contact. Use the official record to reach the sponsor.
14 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ofatumumab in people with Relapsing Multiple Sclerosis, run by Novartis Pharmaceuticals at 14 sites in 2 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 4 inclusion and 4 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 29 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in Japan, Russia. 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 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 18 Feb 2022). 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 Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part (time frame: Baseline up to Week 24). 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 29 Apr 2022.