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

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Brigham and Women's Hospital
• Collaborator: Novartis
• Treatments: Ofatumumab

Criteria

Inclusion Criteria:

• Patients diagnosed with active, relapsing MS course. 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

• Subjects either untreated or treated with disease modifying therapies other than those listed in exclusion criteria

• 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

• None of the exclusion criteria

Exclusion Criteria:

• 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.

• Subjects with active chronic disease (or stable but treated with immune therapy) of the immune system other than MS or with an immunodeficiency syndrome.

• Subjects with a history of the following:

1. History of malignancy

2. History of alcohol or drug abuse

3. Primary or secondary immunodeficiency

4. Prior hematopoietic stem cell transplantation

5. History of transplantation or anti-rejection therapy

• Subjects with abnormal CD19, WBC, lymphocyte counts or abnormal IgG levels

• Subjects with active systemic bacterial, viral or fungal infections, or known to have acquired immunodeficiency syndrome (AIDS).

• Subjects with neurological symptoms consistent with PML or confirmed PML.

• Subjects at risk of developing or having reactivation of syphilis or tuberculosis (eg subjects with known exposure to, or history of syphilis, or active or latent tuberculosis, even if previously treated). Testing for syphilis and tuberculosis will be done at Screening.

• Subjects with low affinity binders (LAB) for TSPO radioligand

• Subjects with abnormal serum creatinine levels

• Subjects with any contraindications to PET/CT or MRI procedures (e.g. claustrophobia, MRI-incompatible implants or pacemakers, renal failure)

• Subjects treated with other disease modifying treatments within their respective pre-specified washout periods will be excluded: