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Efficacy and Safety of Ofatumumab Compared to Placebo in Patients With Relapsing Multiple Sclerosis Followed by Extended Treatment With Open-label Ofatumumab

Primary Purpose

Relapsing Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Ofatumumab
Matching placebo of ofatumumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing Multiple Sclerosis focused on measuring double-blind, placebo controlled, ofatumumab, relapsing multiple sclerosis, Japanese patients, MS, RMS, adult, OMB157

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

OMB 20 mg

Placebo

Arm Description

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.

Placebo subcutaneous injection matching to ofatumumab every 4 weeks for 24 weeks in Core

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part
Blood samples were collected at the scheduled visit. Summary statistics of PK concentrations from trough samples.
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.
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.
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.
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.
Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part
Blood samples were collected at the scheduled visits. Summary statistics of PK concentrations from trough samples.
B-cell Counts - Extension Part
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
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).

Full Information

First Posted
August 11, 2017
Last Updated
April 27, 2022
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03249714
Brief Title
Efficacy and Safety of Ofatumumab Compared to Placebo in Patients With Relapsing Multiple Sclerosis Followed by Extended Treatment With Open-label Ofatumumab
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
March 15, 2018 (Actual)
Primary Completion Date
December 26, 2019 (Actual)
Study Completion Date
July 29, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing Multiple Sclerosis
Keywords
double-blind, placebo controlled, ofatumumab, relapsing multiple sclerosis, Japanese patients, MS, RMS, adult, OMB157

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
64 (Actual)

8. Arms, Groups, and Interventions

Arm Title
OMB 20 mg
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo subcutaneous injection matching to ofatumumab every 4 weeks for 24 weeks in Core
Intervention Type
Drug
Intervention Name(s)
Ofatumumab
Intervention Description
Provided in pre-filled syringes for subcutaneous injection (s.c.) administration containing 20 mg ofatumumab (50 mg/mL, 0.4 mL content)
Intervention Type
Drug
Intervention Name(s)
Matching placebo of ofatumumab
Intervention Description
Matching placebo in pre-filled syringes
Primary Outcome Measure Information:
Title
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Core Part
Description
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.
Time Frame
Baseline up to Week 24
Secondary Outcome Measure Information:
Title
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Japan vs Non-Japan - Core Part
Description
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.
Time Frame
Baseline up to Week 24
Title
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Core Part
Description
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.
Time Frame
Baseline up to Week 24
Title
Annualized Relapse Rate (ARR) - Core Part
Description
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.
Time Frame
Baseline up to Week 24
Title
Pharmacokinetic (PK) Concentrations of Ofatumumab - Core Part
Description
Blood samples were collected at the scheduled visit. Summary statistics of PK concentrations from trough samples.
Time Frame
Pre-dose at Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
Title
B-cell Counts - Japan vs Non-Japan - Core Part
Description
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
Time Frame
Baseline, Days 2, 5, 7, 14, Weeks 4, 12, 24
Title
Number of Gadolinium-enhancing T1 Lesions Per MRI Scan - Extension Part
Description
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.
Time Frame
Week 24 up to Week 48
Title
Number of New or Enlarging T2 Lesions on MRI Scans (Annualized T2 Lesion Rate) - Extension Part
Description
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.
Time Frame
Week 24 up to Week 48
Title
Annualized Relapse Rate (ARR) - Extension Part
Description
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.
Time Frame
Week 24 up to Week 48
Title
Pharmacokinetic (PK) Concentrations of Ofatumumab - Extension Part
Description
Blood samples were collected at the scheduled visits. Summary statistics of PK concentrations from trough samples.
Time Frame
Weeks 24, 28, 36, 48
Title
B-cell Counts - Extension Part
Description
Blood samples were collected at the scheduled visits. The CD19+ B-cell counts were measured by the central laboratory.
Time Frame
Weeks 24, 36 and 48
Title
Participants With Confirmed Relapse - Core and Extension Parts
Description
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).
Time Frame
Baseline up to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Facility Information:
Facility Name
Novartis Investigative Site
City
Toon-city
State/Province
Ehime
ZIP/Postal Code
791-0295
Country
Japan
Facility Name
Novartis Investigative Site
City
Fukuoka city
State/Province
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Sapporo city
State/Province
Hokkaido
ZIP/Postal Code
063-0005
Country
Japan
Facility Name
Novartis Investigative Site
City
Morioka
State/Province
Iwate
ZIP/Postal Code
020-8505
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
980 8574
Country
Japan
Facility Name
Novartis Investigative Site
City
Sendai city
State/Province
Miyagi
ZIP/Postal Code
983 8512
Country
Japan
Facility Name
Novartis Investigative Site
City
Kawagoe
State/Province
Saitama
ZIP/Postal Code
350 8550
Country
Japan
Facility Name
Novartis Investigative Site
City
Kodaira
State/Province
Tokyo
ZIP/Postal Code
187-8551
Country
Japan
Facility Name
Novartis Investigative Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160 8582
Country
Japan
Facility Name
Novartis Investigative Site
City
Chiba
ZIP/Postal Code
260 8677
Country
Japan
Facility Name
Novartis Investigative Site
City
Niigata
ZIP/Postal Code
951 8520
Country
Japan
Facility Name
Novartis Investigative Site
City
Osaka
ZIP/Postal Code
556-0016
Country
Japan
Facility Name
Novartis Investigative Site
City
Kazan
ZIP/Postal Code
420021
Country
Russian Federation
Facility Name
Novartis Investigative Site
City
Novosibirsk
ZIP/Postal Code
630007
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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/.
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=969
Description
A Plain Language Trial Summary is available on novctrd.com

Learn more about this trial

Efficacy and Safety of Ofatumumab Compared to Placebo in Patients With Relapsing Multiple Sclerosis Followed by Extended Treatment With Open-label Ofatumumab

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