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Open Label Randomized Multicenter to Assess Efficacy & Tolerability of Ofatumumab 20mg vs. First Line DMT in RMS

Phase 3
Active, not recruiting
Conditions
Multiple Sclerosis
Interventions
Registration Number
NCT04788615
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

This study will compare ofatumumab vs. European approved platform first line self-administered disease modifying therapy (DMT) in newly diagnosed MS patients

Detailed Description

The study is a randomized (1:1), open-label, rater-blind, multi-center, prospective, parallel-arm, active comparator study which will consist of 15 months treatment period and a 6 months observational safety extension period, for patients who withdraw ofatumumab for any reason, in 186 total patients with early relapsing multiple sclerosis (RMS) RMS patients are patients who are newly diagnosed or have never been on active treatment at the time of study entry with ≤ 5 years from first MS symptoms.

There is a screening period and patients are randomized to either ofatumumab or first line DMT at baseline. Patients will be treated until the end of study (EOS) or for a maximum duration of 15 months. Patients who prematurely discontinue study drug or comparator will have their end of treatment (EOT) visit and assessments at the time of discontinuation. After ofatumumab or the standard of care comparator (DMT) discontinuation, patients may initiate alternative MS therapy according to local standard of care, if clinically indicated.

Patients who for any reason withdraw from ofatumumab during treatment will be invited to participate in the observational extension safety period for 6 months or until patient re-starts MS treatment with a new DMT treatment. During this period, clinical efficacy after ofatumumab withdrawal will be assessed.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
185
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ofatumumabOfatumumabOftatumumab 20mg auto injector syringes for subcutaneous injection on Day 1, Week 1 and 2, followed by subsequent monthly dosing, starting at Month 1.
First line DMTFirst line DMT1. Glatiramer acetate minimum dose 20mg or maximum dose 40mg twice a day or three times a week or 2. Interferon minimum dose 22µg or maximum dose of 0.25mg 3 times a week or once a week or Every second week depending on preparation or 3. Peg-Interferon beta-1a minimum dose of 63µg or maximum dose of 125µg every 2 weeks (14 days) or 4. Teriflunomide 14 mg once a day or 5. Dimethyl fumarate minimum dose of 120mg or maximum dose of 240mg twice a day 6. Diroximel fumarate minimum dose of 231mg or maximum dose of 462mg twice a day
Primary Outcome Measures
NameTimeMethod
Number of participants with no evidence of disease activity (NEDA-3)Baseline to 15 month

NEDA-3 (yes/no) is defined as:

1. Absence of confirmed clinical relapse

2. Absence of new MRI activity (Gd+ T1 lesion or new/enlarged T2 lesion) with MRI re-baselined at Month 3

3. Absence of 3-month confirmed disability worsening

Secondary Outcome Measures
NameTimeMethod
Change in expanded disability status scale (EDSS)Baseline to Month 15

Change in expanded disability status scale (EDSS) from baseline to end of study will be summarized descriptively based on the expanded disability status scale (EDSS) score

Percentage of disability-progression free patientsBaseline to Month 15

Proportion of disability-progression free patients at end of study will be summarized descriptively

The number and percentage of patients with Treatment emergent adverse events (TEAE) or adverse events reportsBaseline to Month 15 and 6 months safety follow-up

Adverse will be collected at each patients visit including any clinically significant safety assessments determined to be an adverse event by the investigator

Number of relapsesBaseline to Month 15

Number of relapses will be summarized descriptively

Annual relapse rateBaseline to Month 15

Annual relapse rate will be analyzed by treatment group using negative binomial regression model with log-link and patient's time in study will be used as an offset.

Percentage of relapse-free patients and proportion of relapse free patients with MRI activity freeMonth 3, Month 9 and Month 15

Proportion of relapse-free patients and proportion of relapse-free patients with MRI activity free at Month 3, 9 and 15 will be summarized descriptively at each timepoint.

Time to 3 month Confirmed Disability Worsening (CDW) and time to 6-month Confirmed Disability Worsening (CDW)Baseline to Month 3 and to Month 6

Time to 3 month Confirmed Disability Worsening (CDW) and time to 6-month CDW will be assessed by EDSS (Expanded disability status scale) score

Number of Gd+ T1 lesions of brainBaseline to Month 15

Number of Gd+ T1 lesions of brain will be summarized descriptively.

Volume of Gd+ T1 lesions of brainBaseline to Month 15

Volume of Gd+ T1 lesions of brain will be summarized descriptively.

Number of new/enlarging T2 lesions of brainBaseline to Month 15

Number of new/enlarging T2 lesions of brain will be summarized descriptively.

Volume of new enlarging T2 lesions of brainBaseline to Month 15

Volume of new enlarging T2 lesions of brain will be summarized descriptively.

Mean time to first relapseBaseline to Month 15

Mean time to first relapse will be summarized descriptively

Percentage of SAEs, and SAEs with hospitalizationsBaseline to Month 15 and 6 months safety follow-up

Proportion of SAEs, and SAEs with hospitalizations between ofatumumab 20 mg s.c. and first line self-administered DMTs

Percentage of treatment compliance of participantsBaseline to Month 15

Treatment compliance will be assessed by review of participant diary entries and counts of treatment (dispensed and returned)

Percentage of patient with AEsBaseline to Month 15 and 6 months safety follow-up

Proportion of patients with adverse events, including injection related reactions

Percentage of withdrawn patientsBaseline to Month 15

Proportion of patients who withdrew due to abnormal lab values

Percentage of treatment discontinuation or interruptionsBaseline to Month 15

Proportion of treatment discontinuation or interruptions for safety/ tolerability reason

Trial Locations

Locations (1)

Novartis Investigative Site

🇪🇸

Valencia, Spain

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