Dimethyl Fumarate for Multiple Sclerosis

(CONNECT Trial)

Recruiting at 118 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

156 Participants Needed

Trial Summary

What is the purpose of this trial?

The main objectives of Part 1 are as follows: To evaluate the safety, tolerability, and efficacy of BG00012 in pediatric subjects with RRMS, as compared with a disease-modifying treatment and to assess health outcomes and evolution of disability. The primary objective of Part 2 is to evaluate the long-term safety of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306. The secondary objective of Part 2 is to describe the long-term MS outcomes of BG00012 in subjects who completed Week 96 in Part 1 of Study 109MS306.

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.

What data supports the effectiveness of the drug Dimethyl Fumarate for Multiple Sclerosis?

Research shows that Dimethyl Fumarate (DMF) is effective in reducing disease activity in patients with relapsing-remitting multiple sclerosis, as seen in MRI scans and clinical trials. It has anti-inflammatory and protective effects on nerve cells, making it a beneficial treatment for this condition. ^{1 2 3 4 5}

Is dimethyl fumarate safe for humans?

Dimethyl fumarate, used for treating multiple sclerosis, is generally safe for humans. Common side effects include flushing and stomach issues like diarrhea and nausea, mostly in the first few months. Serious side effects were not more frequent than with a placebo over two years. ^{1 3 6 7 8}

How is the drug dimethyl fumarate unique for treating multiple sclerosis?

Dimethyl fumarate is unique because it is an oral medication, unlike many other treatments for multiple sclerosis that require injections. It also has dual anti-inflammatory and neuroprotective effects, which may help reduce disease activity and protect nerve cells. ^{1 3 4 9 10}

Research Team

Medical Director

Principal Investigator

Biogen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study. [2018]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Transient hair loss during treatment with dimethyl-fumarate for multiple sclerosis. [2017]

4. United States pubmed.ncbi.nlm.nih.gov

Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (BG-12) for the treatment of multiple sclerosis. [2015]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Dimethylfumarate in the treatment of relapsing-remitting multiple sclerosis]. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate (Tecfidera): a new oral agent for multiple sclerosis. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Dimethyl fumarate for multiple sclerosis. [2015]