Intravenous Immunoglobulin for Muscular Dystrophy

Recruiting at 4 trial locations

Overseen By Hannah E Howell, MS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Must not be taking: Statins, Rituximab, Biologics, others

Disqualifiers: Anaphylaxis to IVIG, Cardiovascular events, others

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

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

Compensation: Varies

Number of Visits: 7

Duration: 12 weeks

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called intravenous immunoglobulin (IVIG) to determine its effectiveness for individuals with anti-HMGCR immune-mediated necrotizing myopathy, a type of muscle weakness disorder. Participants will receive either the IVIG treatment or a placebo (a harmless saltwater solution) to compare effects. The goal is to assess whether IVIG can improve muscle strength and ensure safety for those with this condition. Individuals who have tested positive for anti-HMGCR antibodies and have had the condition for less than three years might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications, but you cannot use more than one oral DMARD, change your DMARD dose within 4 weeks before screening, or use certain medications like rituximab, plasma exchange, or statins before joining. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that intravenous immunoglobulin (IVIG) is generally safe for people with various health issues, including nerve and muscle disorders. One study found that 26% of patients experienced side effects, but most were minor, and all patients recovered. Other research indicates that IVIG remains safe even with long-term use. While some caution is necessary, patients often tolerate it better than other treatments. Notably, IVIG is already approved for other conditions, which supports its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for muscular dystrophy, which typically involve corticosteroids and physical therapy to manage symptoms, the new approach with Intravenous Immunoglobulin (IVIG) offers a unique mechanism. IVIG is derived from pooled human immunoglobulin and is administered directly into the bloodstream, potentially offering a new way to modulate the immune system and reduce muscle inflammation. Researchers are excited about IVIG because it could provide a more targeted treatment with the possibility of slowing disease progression, which current therapies don't address directly.

What evidence suggests that this treatment might be an effective treatment for muscular dystrophy?

Research shows that intravenous immunoglobulin (IVIG), which participants in this trial may receive, can help treat certain autoimmune and nerve-muscle disorders. Studies have found that IVIG can lower disease activity and reduce the need for other medications like steroids. In patients with conditions similar to muscular dystrophy, IVIG has been linked to improvements in disability within a few weeks. Although side effects can occur, they are usually minor and resolve on their own. While IVIG is used for various nerve-muscle issues, information on its use for specific conditions like anti-HMGCR IMNM is still being gathered. Overall, IVIG appears to be a promising treatment option for nerve-muscle disorders. ^{2 6 7 8 9}

Who Is on the Research Team?

James Andrews, MD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for individuals with active anti-HMGCR immune-mediated necrotizing myopathy (IMNM), a muscle disease. Participants must meet specific health criteria to join and be willing to potentially receive a placebo. Those who have conditions that might interfere with the study or its results are not eligible.

Inclusion Criteria

I am 16 years old or older.

My muscle disease started less than 3 years ago.

I have tested positive for anti-HMGCR antibodies.

Exclusion Criteria

I am currently taking statin medication.

I am not pregnant, breastfeeding, and am willing to use effective birth control during the study.

Wells' Criteria for Deep Vein Thrombosis score of 2 or more at screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to receive either IVIG or placebo at weeks 0, 4, and 8

12 weeks

3 visits (in-person)

Open-label extension

Participants receive IVIG at weeks 12, 16, and 20

12 weeks

3 visits (in-person)

Follow-up

Participants return at week 24 for a final non-infusion visit to reassess safety, tolerability, and efficacy outcome

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Intravenously administered pooled human immunoglobulin (IVIG)

Trial Overview The MIGHT Trial is testing the effects of IVIG, an intravenous treatment made from pooled human immunoglobulin, on IMNM. Half of the participants will receive IVIG and half will get a saline solution as placebo, randomly assigned. The main outcomes will be measured at week 12.

How Is the Trial Designed?

Group I: Intravenously Administered Pooled Human Immunoglobulin (IVIG) Experimental Treatment 1 Intervention

Participants will receive intravenously administered pooled human immunoglobulin (IVIG) 2g/kg every 4 weeks for 24 weeks.

Group II: Placebo Active Control 1 Intervention

Participants will receive an infusion of 0.9% sodium chloride solution every 4 weeks for 16 weeks at equivalent volume to corresponding IVIG weight-based dose.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Octapharma USA, Inc.

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

A study of 345 pediatric patients receiving intravenous immunoglobulin (IVIG) at Hamad General Hospital found that IVIG has a good safety profile, with low incidence of severe adverse drug reactions (ADRs) such as fever (5.8%) and chills (2.6%).

The only significant factor associated with the occurrence of ADRs was the specific brand of IVIG used, indicating that different formulations may have varying safety profiles, and further research is needed to explore this relationship.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of intravenous immunoglobulin in pediatric patients: a retrospective, 1-year observational study. Elajez, R., Ezzeldin, A., Gaber, H.[2022]

In a study of 305 intravenous immunoglobulin G (IVIG) infusions given to 111 pediatric patients, only 3.9% of infusions resulted in adverse reactions, indicating a low incidence of side effects in this population.

The most severe adverse reactions included two cases of aseptic meningitis and one case of seizures, all of which resolved completely, suggesting that while IVIG is generally safe, monitoring for rare severe reactions is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin G use and pharmacovigilance in a tertiary care children's hospital. Yori, S., Belleri, F., Testard, J., et al.[2021]

Intravenous immunoglobulin (IVIG) preparations, developed to be well tolerated and safe for administration, have transformed the treatment of immunodeficiency syndromes and are effective in preventing infections in patients with compromised immune systems.

IVIG is also beneficial in treating certain autoimmune diseases, potentially due to its ability to inhibit harmful immune responses and protect cells from damage, showcasing its versatility beyond just infection prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Historic aspects of intravenous immunoglobulin therapy. Good, RA., Lorenz, E.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4720677/

Efficacy of Intravenous Immunoglobulin in Neurological ... Of interest, pooled data have shown that serum IgG levels are higher by 10–20 % (mean 13 %) with weekly SCIG compared with monthly IVIG [96]. After 6–12 weekly ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1568997224002015

Intravenous immunoglobulin as a therapy for autoimmune ... The results demonstrated a notable efficacy of immunoglobulin in reducing disease activity and in tapering the dose of systemic corticosteroids ...

3. withpower.com withpower.com/trial/intravenous-immunoglobulin-for-muscular-dystrophy-56147

Intravenous Immunoglobulin for Muscular Dystrophy In a study of rapid infusion in patients with neuromuscular disorders, 26% experienced adverse events, most of which were minor, and all patients recovered ...

4. touchneurology.com touchneurology.com/neuromuscular-diseases/journal-articles/patient-reported-outcomes-an-emerging-cornerstone-of-effective-intravenous-immunoglobulin-therapy/

Patient-reported Outcomes—An Emerging Cornerstone of ... IVIG is used to treat a range of neuromuscular disorders, however, there are limited data supporting home treatment of some of these diseases.

5. neurologylive.com neurologylive.com/view/updated-review-highlights-efficacy-intravenous-immunoglobulin-cidp

Updated Review Highlights Efficacy of Intravenous ... IVIg demonstrates a significant increase in the probability of disability improvement in patients with CIDP in 2 to 6 weeks, comparable with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8316973/

Role of Immunoglobulins in Muscular Dystrophies and ... Here we focus on mechanisms of action of immunoglobulins in muscular dystrophies and inflammatory myopathies highlighting results of IVIGs from pre-clinical ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923009376

Efficacy of Intravenous Immunoglobulin in Neurological ... Although, IVIG is considered safe for long-term administration, compared with other effective therapeutic modalities such as PE, corticosteroids, or ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10531894/

Efficacy and Safety of Intravenous Immunoglobulin Treatment ... In the vast majority of cases, patients with MG achieved neurological improvement after IVIg treatment.

9. academic.oup.com academic.oup.com/rheumatology/article/60/4/1784/5939817

Intravenous immunoglobulins as first-line treatment in ... Treatment response was mostly reached by 3 weeks of IVIg treatment in the responders. Although generally safe and feasible, caution is advocated ...