9-month Study to Assess the Efficacy of Ofatumumab on Microglia in Patients With Relapsing Forms of Multiple Sclerosis

NCT04510220 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 2020P002078
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

We aim to assess the effect of Ofatumumab on microglial activation using \[F-18\]PBR06 PET in MS patients in relation to changes in serum markers, MRI abnormalities and clinical impairment longitudinally over 9 months. Specific Aims: Specific Aim 1: To determine the effect of Ofatumumab on microglial activation in MS over 9 months. Specific Aim 2: To determine the time course of effect of Ofatumumab on microglial activation and its relationship with peripheral B-cell depletion, serum neurofilament light (sNfL) chain and glial-fibrillary acid protein (GFAP) levels and other serum biomarkers Specific Aim 3: To determine the relationship of PET changes following Ofatumumab initiation with 3T MRI changes and clinical parameters.

Conditions

Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Glial Activity Load on PET

  The primary endpoint of the study will be the regional glial activity on PET (GALP) measurements at 3 months and 9 months compared to baseline. Individualized z-score maps of brain parenchymal microglial activation were generated using a voxel-by-voxel comparison between each subject's 60-90 minute PET standardized uptake value ratio (SUVR) images (globally normalized) and a control dataset of 9 healthy individuals. GALP scores were calculated as the sum of voxel-by-voxel z-scores \>4 in a given region divided by the total number of voxels in that region. A z-score of 0 represents the reference population mean. Higher z-scores indicate worse outcomes. A z-score \>4 is considered positive and contributes to the average GALP score.

  Baseline, 3 Months, and 9 Months

Secondary Outcomes (1)

• % CD19 Counts

  Baseline, 5 Days, and 9 Months

Study Arms (1)

Subjects diagnosed with relapsing forms of multiple sclerosis

EXPERIMENTAL

We plan to enroll 10 subjects with relapsing MS. All enrolled subjects will receive Ofatumumab 20 mg every 4 weeks, subcutaneously for 9 months during the study. Loading doses will be administered initially at 1, 7 and 14 days. During the study period, all enrolled subjects will undergo five PET scans using \[F-18\] PBR06 at day 0, 5, 28, 90 (3 Months) and 273 (9 Months) after starting treatment with Ofatumumab.

Drug: Ofatumumab; Drug: [F-18]PBR06

Interventions

Ofatumumab DRUG

Ofatumumab (OMB157) is a fully human anti-CD20 monoclonal antibody (mAb) self-administered by a once-monthly subcutaneous injection that is in development for MS. Ofatumumab drug product (also referred as OMB157) is formulated as 20 mg/0.4 mL (50 mg/mL) solution for injection, provided in autoinjectors, for subcutaneous administration. The autoinjectors contain a small overfill to allow for a complete withdrawal of the labeled amount (20 mg) of ofatumumab.

Also known as: OMB157

Subjects diagnosed with relapsing forms of multiple sclerosis

[F-18]PBR06 DRUG

PET radiopharmaceutical. Subjects will undergo \[F-18\]PBR06-PET (microglial activation).

Also known as: [18F]PBR06

Subjects diagnosed with relapsing forms of multiple sclerosis

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients diagnosed with active, relapsing MS course (defined by Lublin 2014 criteria). Active disease is defined by at least 1 relapse during the previous 1 year or 2 relapses during the previous 2 years or a positive gadolinium-enhancing MRI scan or MRI scan with new or unequivocally enlarging T2 lesions in previous year.
• Age 18 to 60 years
• EDSS 0 to 5.5

You may not qualify if:

• Agree to start treatment with ofatumumab and comply with study procedures for the duration of the study
• No other systemic disease or neurological disorders requiring chronic or acute steroid or other immunosuppressive treatment
• No known hypersensitivity reactions to contrast agents
• Subjects suspected of not being able or willing to cooperate or comply with study protocol requirements in the opinion of the investigator.
• Subjects with primary progressive MS or SPMS without disease activity.
• Disease duration of more than 10 years in patients with an EDSS score of 2 or less
• Subjects meeting criteria for neuromyelitis optica.
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for at least 6 months after stopping study medication. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the subject, if accepted by the local regulation). NOTE: Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal ARE NOT acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment
• For female subjects on the study, the vasectomized male partner should be the sole partner
• Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%), for example hormone vaginal ring or transdermal hormone contraception. In case of use of oral contraception, women should have been stable on the same pill for a minimum of 3 months before taking investigational drug.
• In case local regulations deviate from the contraception methods listed above, local regulations apply and will be described in the ICF.
• Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Novartis: collaborator

Study Sites (1)

Brigham MS Center, 60 Fenwood Road

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

ofatumumab; N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline

Results Point of Contact

• Title: Dr. Tarun Singhal
• Organization: Brigham and Women's Hospital

tsinghal@bwh.harvard.edu

617-264-3043

Study Officials

• Tarun Singhal, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: July 31, 2020
• First Posted: August 12, 2020
• Study Start: September 21, 2020
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Locations

US (1)