Fecal Microbiota Transplantation (FMT) of FMP30 in Relapsing-Remitting Multiple Sclerosis

• Status: Active, not recruiting
• Trial end date: 2022-01-01
• Target enrollment: 0
• Participant gender: All

Summary

In this Phase 1b open-label prospective clinical trial, patients with relapsing-remitting MS will undergo FMT of FMP30 (donor stool) via colonoscopy and immunological efficacy endpoints will be assessed at various time points. The active phase of the study will continue for 12 weeks post-FMT with safety and biomarker (engraftment) follow-up for 48 weeks. A parallel observational control arm of MS patients who otherwise satisfy study inclusion criteria based on their MS phenotype, demographics, disease duration and prior use of allowable MS therapies, will be recruited as a comparison observational group to measure stability of stool and serum immunological measures. The study duration for the Observational Control Arm is 12 weeks.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Jeffrey Gelfand; University of California, San Francisco

Criteria

Inclusion Criteria:

1. Age 18-60 inclusive (at time of screening).

2. Diagnosis of relapsing-remitting multiple sclerosis (MS) by International Panel McDonald Criteria (2010)(1) incorporating 2017 revisions which reclassify select high-risk Clinically Isolated Syndromes under 2010 criteria as RRMS under 2017 criteria, and Lublin criteria (2014)(2).

3. Recent documented MS disease activity, defined as at least 1 clinical relapse within the past 1 year prior to baseline OR 2 clinical relapses in the past 2 years prior to baseline OR at least 1 new T2/FLAIR lesion on brain or spine MRI OR at least 1 gadolinium enhancing lesion on brain or spine MRI in the past 1 year prior to baseline.

4. Expanded Disability Status Scale (EDSS) less than or equal to 6.0; EDSS 5.5 or less if MS disease duration is greater than 15 years (no other disease duration restriction).

5. Must have positive serology for Epstein-Barr Virus (EBV) (IgG anti-EBNA positive) at screening, indicating prior exposure.

6. No prior MS disease modifying therapy or a 12 week washout period for subjects on glatiramer acetate or interferon-beta therapy.

7. At least 4 weeks from baseline since last use of IV or oral glucocorticoids Protocol:

MS-BIOME Study.

8. Agree to maintain a stable diet during the course of the study (over the counter probiotics are allowable).

9. Premenopausal women and women <12 months after the onset of menopause must have a negative serum pregnancy test unless they have undergone surgical sterilization.

10. Female subjects of childbearing potential who are sexually active with a non-sterilized male partner must agree to use a highly effective method of contraception; non-sterilized male subjects who are sexually active with a female partner of childbearing potential must agree to use a highly effective method of contraception.

11. Not actively participating in another interventional MS clinical trial (participation in other observational research studies is allowable).

Exclusion Criteria:

1. Prior use of fingolimod, dimethyl fumarate, teriflunomide, natalizumab, alemtuzumab, mitoxantrone, cyclophosphamide, rituximab, ocrelizumab, daclizumab, methotrexate, azathioprine, mycophenolate mofetil, cyclosporine, leflunomide or induction chemotherapy.

2. No use of diuretics like furosemide (Lasix) 1 week before the first dose oral antibiotics. The use of hydrochlorothiazide (HCTZ) for hypertension at a dose < 50 mg/day is allowable.

3. Progressive MS by Lublin criteria (2014).

4. No oral or IV antibiotics within 8 weeks of screening and 12 weeks of scheduled of the planned FMT procedure if in the FMT arm or first stool collection if in control arm (note that topical, otic, ocular antibiotics are specifically allowable which is consistent with the IMSMS.org protocol for collaborative gut microbiome research in MS).

5. Hypersensitivity or allergy to study antibiotics, conscious sedation medications or bowel preparation.

6. Contraindication to study procedures including MRI, anesthesia (ASA criteria IV and V), colonoscopy, phlebotomy.

7. History of inflammatory bowel disease (Crohn's Disease, Ulcerative Colitis) Protocol:

MS-BIOME Study.

8. Active symptomatic C. Difficile infection (colonization is not an exclusion).

9. Active gastrointestinal condition being investigated (i.e. GI bleeding, colon cancer, active GI workup); history of known or suspected toxic megacolon and/or known small bowel ileus, major gastrointestinal surgery (e.g. significant bowel resection) within 3 months before enrollment (note that this does not include appendectomy or cholecystectomy); or history of total colectomy or bariatric surgery.

10. History of malignancy (except excised cutaneous basal cell carcinoma or squamous cell carcinoma which are allowable) including no concurrent induction chemotherapy, radiation therapy or biological treatment for active malignancy.

11. Pregnant or lactating women or intention of getting pregnant during the trial period.

12. Active infection including untreated latent or active tuberculosis, HIV, hepatitis, syphilis or other major active infection.

13. Known immunodeficiency including CVID.

14. INR>1.5, Platelets<100, Hemoglobin <8.5, WBC<2.0, Absolute lymphocyte count <0.8, Absolute Neutrophil Count <0.5, CD4<200, eGFR<45.

15. Any condition that in the opinion of the study PI could jeopardize the safety of the subject, would make it unlikely for the subject to complete the study or could confound the results of the study.

16. Unable or unwilling to comply with study protocol requirements.