Dimethyl Fumarate for Multiple Sclerosis

(CONNECT Trial)

No longer recruiting at 137 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Biogen

Must not be taking: Steroids, Monoclonal antibodies

Disqualifiers: Progressive MS, Autoimmune disorders, Cancer, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called BG00012 (Dimethyl Fumarate) for individuals with relapsing-remitting multiple sclerosis (RRMS), a condition where the immune system mistakenly attacks the brain and spinal cord. The trial aims to determine if BG00012 is safe and effective, particularly in its impact on symptoms and disability progression over time. Participants will receive either BG00012 or a different treatment, Avonex (Interferon β-1a), for comparison. Suitable candidates for this trial include those diagnosed with RRMS who can walk and have experienced recent relapses or specific brain scan findings related to MS. As a Phase 3 trial, this study serves as the final step before potential FDA approval, offering participants an opportunity to contribute to the development of a promising treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. Specifically, you must not have taken steroids or certain other medications within 30 days before starting the trial, and some treatments must not have been used within 6 to 12 months prior.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that dimethyl fumarate (also called BG00012) is generally safe for people with relapsing-remitting multiple sclerosis (RRMS). Studies indicate that most people can take it without serious issues.

Earlier research found that some patients experienced side effects like skin redness and warmth (flushing) and stomach problems. However, these effects were usually mild and manageable. Long-term studies also support its safety, confirming it is safe for extended use.

For those considering joining a trial with this treatment, this information suggests it has been well-studied and is considered safe for many people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple sclerosis?

Most treatments for multiple sclerosis (MS) work by modifying the immune response to reduce inflammation, such as interferon beta-1a (Avonex), which is commonly used. However, BG00012, also known as dimethyl fumarate, offers something different. This treatment works by activating the Nrf2 pathway, which helps protect nerve cells from stress and damage. Researchers are excited about BG00012 because it not only modulates the immune system but also provides neuroprotection, potentially reducing relapses and slowing disease progression in a novel way. Plus, it's taken orally, making it more convenient compared to injectable treatments.

What evidence suggests that this trial's treatments could be effective for multiple sclerosis?

Research has shown that dimethyl fumarate (DMF), which participants in this trial may receive, effectively treats relapsing-remitting multiple sclerosis (RRMS). Studies have found that DMF can lower the number of attacks and reduce new brain lesions. It also carries a lower risk of relapses compared to some other initial treatments for RRMS. Clinical trials have confirmed that DMF is both effective and safe for people with this type of MS. These findings suggest DMF could be a promising option for managing RRMS symptoms. Another treatment option in this trial is Interferon β-1a (Avonex), which researchers will compare to DMF in terms of effectiveness and safety. ^{6 7 8 9 10}

Who Is on the Research Team?

Medical Director

Principal Investigator

Biogen

Are You a Good Fit for This Trial?

This trial is for kids over 30 kg with Relapsing-remitting Multiple Sclerosis (RRMS) who can walk and have had recent MS activity but no relapse or steroids in the last 50 days. They must not have other similar diseases, severe allergies to the drugs being tested, or any major health issues that could interfere with the study.

Inclusion Criteria

Subjects of childbearing potential who are sexually active must be willing to practice effective contraception during the study and be willing and able to continue contraception for at least 30 days after their final dose of study treatment

My body weight is at least 30 kg.

I have been diagnosed with relapsing-remitting MS.

Exclusion Criteria

I have a history of HIV.

History of abnormal laboratory results indicative of any significant endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, renal, and/or any other major disease that would preclude participation in a clinical study

Other unspecified reasons that, in the opinion of the Investigator or Biogen Idec, make the subject unsuitable for enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BG00012 or IFN β-1a for up to 96 weeks to evaluate safety, tolerability, and efficacy

96 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of BG00012 treatment to evaluate long-term safety and MS outcomes

Up to 7 years

What Are the Treatments Tested in This Trial?

Interventions

• BG00012
• Dimethyl Fumarate
• Interferon β-1a

Trial Overview The trial tests BG00012 against a standard treatment for pediatric RRMS. It aims to see if BG00012 is safe, tolerable, and effective in managing symptoms and slowing disability progression over time compared to existing treatments.

How Is the Trial Designed?

Group I: BG00012 Experimental Treatment 1 Intervention

Participants will receive the recommended dose of 240 mg orally, twice a day

Group II: IFN β-1a (Avonex) Active Control 1 Intervention

Participants will receive the recommended dose of 30 μg (weekly)

Who Is Running the Clinical Trial?

Biogen

Lead Sponsor

Trials

655

Recruited

468,000+

Daniel Quirk

Biogen

Chief Medical Officer

MD

Christopher A. Viehbacher

Biogen

Chief Executive Officer since 2022

Graduated from Queen's University, Kingston, Ontario, Canada

Published Research Related to This Trial

Dimethyl fumarate is a new oral medication for treating multiple sclerosis (MS) that has shown promising results in both experimental and clinical studies, particularly regarding its mechanism of action and safety profile.

The review discusses clinical trial data, including MRI results, which support the drug's tolerability and its role in the current treatment landscape for MS, along with a risk management plan for potential adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dimethylfumarate in the treatment of relapsing-remitting multiple sclerosis]. Popova, EV., Boyko, AN., Orlova, EV.[2018]

Dimethyl fumarate has been shown to significantly reduce relapse rates in patients with relapsing-remitting multiple sclerosis (MS), with a reduction of 34% to 49% in the proportion of patients experiencing relapses over two years, based on two phase III trials (DEFINE and CONFIRM).

The safety profile of dimethyl fumarate is comparable to placebo, with serious adverse effects occurring at similar rates; however, some patients experienced intolerable flushing and gastrointestinal issues, leading to discontinuation in 3% and 4% of cases, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. Venci, JV., Gandhi, MA.[2015]

In a study of 735 patients with relapsing-remitting multiple sclerosis, dimethyl-fumarate (DMF) reduced the annual relapse rate by 63.2%, with 85% of patients relapse-free at 12 months.

DMF was found to be safe, with the most common side effects being flushing (37.2%) and gastro-enteric issues (31.1%), and it showed significant benefits for both treatment-naïve patients and those switching from other therapies due to tolerability or efficacy concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study. Mallucci, G., Annovazzi, P., Miante, S., et al.[2018]

In a study of 257 patients with relapsing-remitting multiple sclerosis, BG00012 at a dose of 240 mg three times daily significantly reduced the mean total number of new gadolinium-enhancing lesions by 69% compared to placebo, indicating strong efficacy in reducing disease activity.

BG00012 also decreased the annualized relapse rate by 32%, although this result was not statistically significant, and it was associated with some adverse events like abdominal pain and flushing, suggesting a generally favorable safety profile that supports further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Kappos, L., Gold, R., Miller, DH., et al.[2022]

Dimethyl-fumarate, an approved treatment for relapsing-remitting Multiple Sclerosis, was well-tolerated by a 55-year-old woman, with the only notable side effect being moderate flushing.

Although transient hair loss was not previously reported as a side effect of dimethyl-fumarate, it was observed in this patient after starting the therapy, but it resolved after two months, suggesting a possible link to the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis. Losavio, FA., Lucchini, M., De Fino, C., et al.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7036051/

Effectiveness and side effects of dimethyl fumarate in ... The results of the present clinical trial showed that treatment of relapsing MS with DMF would provide decreased attack rate and GD lesions. Moreover, most of ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34505304/

Comparative effectiveness of dimethyl fumarate in multiple ... Conclusion: DMF is associated with lower risk of treated relapse for patients with RRMS than other first-line RRMS agents (TERI and IIM). Keywords: cohort study ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1114287

Placebo-Controlled Phase 3 Study of Oral BG-12 for ... Biogen Idec announces positive top-line results from second phase 3 trial investigating oral BG-12 (dimethyl fumarate) in multiple sclerosis.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01930708?term=AREA%5BBasicSearch%5D(BG-12)&rank=3

A Study Evaluating the Effectiveness of Tecfidera (Dimethyl ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034819309435

Clinical predictors of Dimethyl Fumarate response in ... Dimethyl-fumarate (DMF) was effective and safe in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39570545/

Real-World Safety and Effectiveness of Dimethyl Fumarate in ... Introduction: Real-world studies in the USA report that 41-56% of patients with multiple sclerosis (MS) are ≥ 50 years old, yet data on their ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00835770

Study Details | NCT00835770 | BG00012 Monotherapy ... The primary objective of this study is to evaluate the long-term safety profile of BG00012 (dimethyl fumarate). Secondary objectives of this study are to ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39673658/

Long-Term Safety and Effectiveness of Dimethyl Fumarate ... Dimethyl fumarate (DMF) has demonstrated a favorable benefit-risk profile in patients with relapsing-remitting multiple sclerosis (RRMS) in clinical and real- ...

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034820306404

Safety of dimethyl fumarate for multiple sclerosis We summarized the proportion of DMF-exposed patients affected and calculated the risk ratios (RR) and number needed to treat for an additional harmful outcome ( ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT01838668?term=AREA%5BInterventionSearch%5D(BG-00012)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=7

An Efficacy and Safety Study of BG00012 (Dimethyl ... The primary objective in Part I of this study is to determine the efficacy of BG00012 (dimethyl fumarate, DMF) on inflammatory brain magnetic resonance imaging ...