Investigating Indirect Mechanism of Neuroprotection of Tecfidera® (Dimethyl Fumarate) in RRMS and Progressive Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03092544
• Date of registration: 23/06/2016
• Prospective Registration: No
• Primary sponsor: Multiple Sclerosis Center of Northeastern New York
• Public title: Investigating Indirect Mechanism of Neuroprotection of Tecfidera® (Dimethyl Fumarate) in RRMS and Progressive Patients
• Scientific title: Investigating Indirect Mechanism of Neuroprotection of Tecfidera® (Dimethyl Fumarate) in RRMS and Progressive Patients
• Date of first enrolment: February 2015
• Target sample size: 57
• Recruitment status: Unknown status
• URL: https://clinicaltrials.gov/show/NCT03092544
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Keith R Edwards, M.D.
• Affiliation: MS Center of Northeastern NY

Key inclusion & exclusion criteria

Inclusion Criteria:

Inclusion (MS Population Only)

Subjects must meet all of the following inclusion criteria to be eligible for enrollment
into the study:

1. Male or female subject, age 18-65 (inclusive) at the time of informed consent, with a
confirmed diagnosis of multiple sclerosis and meeting multiple sclerosis patient
population as specified in section 4/ study design/multiple sclerosis population of
this protocol.

2. Subject has the ability to understand the purpose and risks of the study and provide
signed and dated informed consent and authorization to use protected health
information (PHI) in accordance with national and local subject privacy regulations.

3. Expanded Disability Status Scale (EDSS) score between 0 and 7, inclusive, at screen.

Exclusion (MS Population Only)

General and Medical History Exclusions

1. A MS relapse, as determined by the investigator, that occurred within 90 days prior to
screen or the subject has not stabilized from a previous relapse prior to screen
visit.

2. Current smoker

3. Any contraindication to having a brain MRI (e.g. pacemaker, MRI-incompatible aneurysm
clips, artificial heart valves, or other metal foreign body; claustrophobia that
cannot be medically managed) or contraindication for administration of
gadolinium-contrast agents.

4. Clinically significant brain MRI findings other than those related to MS, as judged by
the investigator, at screen.

5. Any contraindications to having a Lumbar puncture (LP) (i.e. Aspirin (ASA) greater
than 325mg/day, Coumadin, Plavix, decreased platelet count) as determined by the
investigator.

6. History of Chronic Urinary Tract Infections, Irritable Bowel Syndrome, Inflammatory
Bowel Disease, Diabetes Mellitus or vascular disease as determined by history and
investigator decision

7. Evidence or history of autoimmune disease (e.g., rheumatoid arthritis, systemic lupus
erythematosus, ulcerative colitis, diabetes mellitus or others) with the exception of
MS.

8. History of or current clinically relevant gastrointestinal bleeding or other
gastrointestinal diseases or processes that may interfere with the analysis of stool
samples per protocol.

9. Any sign of chronic active infection (e.g. urinary tract infection (UTI), bronchitis,
hepatitis and tuberculosis) except for those requiring topical medication for
treatment (e.g., athletes foot), or screening laboratory evidence consistent with a
significant chronic active acute infection requiring systemic treatment. This must be
resolved before treatment may commence, (e.g., acute respiratory tract, urinary tract,
or gastrointestinal tract infections).

10. Pregnant females; breastfeeding females and/or males of childbearing potential;
females of childbearing potential who are unwilling or unable to use a highly
effective method of contraception as outlined in this protocol for the duration of the
study and for at least 28 days after the last dose of dimethyl fumarate use in this
protocol. For females of childbearing potential in the dimethy fumarate population; a
positive pregnancy test at anytime within the protocol.

11. Known Positive HIV antibody, hepatitis B surface antigen (HBsAg), hepatitis B core
antibody (HBcAb), or hepatitis C antibody tests indicative of present or prior
infection.

12. Any abnormal hematology values or clinical chemistry values judged by the Investigator
or Sponsor as clinically significant.

13. Positive purified protein derivative (PPD) skin test or positive quantiferon (QTFN) at
screen visit or know history of active tuberculosis not adequately treated.

14. Any malignancy within 5 years, except for basal or Squamous cell skin lesions which
have been surgically excised, with no evidence of metastasis.

15. Any clinical, CSF or MRI evidence for Progressive multifocal leukoencephalopathy
(PML), from historical MRI or results of the screen MRI.

16. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation of
study results and, in the judgment of the investigator, would make the subject
inappropriate for entry into this study.

17. Subjects participating in or expecting to participate in other interventional clinical
trials.

18. Inability or unwillingness to record online dietary questionnaire information as
required by protocol

19. History of drug or alcohol abuse (as defined by the investigator) within 2 years prior
to screen.

Exclusion Criteria related to Medication

20. Previous Exposure to dimethy fumarate for disease management at any time in the past.

21. Treatment with methylprednisolone or other systemic corticosteroid for multiple
sclerosis relapse or otherwise within 30 days prior to day one of IP administration.

22. Treatment with multiple sclerosis disease modifying therapies as follows:

- Beta interferons (interferon beta-1a [Avonex® or Rebif®] or interferon beta-1b
[Betaseron®], or glatiramer [Copaxone®] within 6 weeks prior to Baseline.

- Fingolimod (Gilenya®), Teriflunomide (Aubagio®) or washout with accelerated
elimination and verification of zero serum levels of teriflunomide prior to day
one baseline)

- Tysabri® (Natalizumab)

- within 6 months prior to screen OR

- one month prior to screen if subject has a positive Nabs to Tysabri®

- Treatment within the past 5 years or current treatment with any of the following
agents: cyclosporine, cladribine, that are immunosuppressive (e.g. rituximab,
etanercept, cellcept, others), murine protein, T-cell vaccination,
plasmapheresis, IV immunoglobulin (IgG) or stem cell transplantation prior to
screen.

23. Receipt of any non-live vaccine within the previous 14 days or live vaccine within 30
days prior to first dose of investigational product (IP).

24. Treatment with an investigational drug within 30 days or 5 half-lives preceding the
first dose of study medication, whichever is longer.

25. Use of antibiotics for any reason within 3 months of screen.

Inclusion (Normal Control Volunteer Only)

Subjects must meet all of the following inclusion criteria to be eligible for enrollment
into the study:

1. Normal control volunteer meeting age and co


Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Multiple Sclerosis

Intervention(s)

Drug: dimethyl fumarate

Primary Outcome(s)

changes in microbiota composition consequent to dimethyl fumarate treatment. [Time Frame: 6 months of therapy]

Change in cerebrospinal (CSF) samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics [Time Frame: change from baseline at 6 months treatment with dimethyl fumarate]

change in levels of ceramide sphyngosine and other lipid species in samples collected from patients before and after therapy in CSF samples in RRMS patients [Time Frame: at baseline and 6 months of therapy]

Change in plasma samples collected from stable RRMS patients on dimethyl fumarate for their ability to induce changes in neuronal bioenergetics [Time Frame: change from baseline at 6 months treatment with dimethyl fumarate]

change in levels of neurofilament( NFL) in RRMS patients [Time Frame: at baseline and after 6 months of therapy]

Secondary ID(s)

BG12-002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Biogen

Icahn School of Medicine at Mount Sinai