Iptacopan for Myasthenia Gravis

Recruiting at 64 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: NSISTs, Steroids

Must not be taking: Complement inhibitors, Anti-FcRn therapies

Disqualifiers: Infections, Pregnancy, Recent thymectomy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 months

146 Participants Needed

Trial Summary

What is the purpose of this trial?

The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in patients with AChR+ gMG who are on stable SOC treatment. Participants who meet the eligibility criteria will be randomized in a ratio of 1:1, to receive either iptacopan or matching placebo, for 6 months (180 days) while continuing on a stable SOC treatment. The randomization will be stratified based on region.

Will I have to stop taking my current medications?

The trial does not require you to stop your current medications. Participants will continue on a stable standard of care treatment while taking the study drug or placebo.

How is the drug Iptacopan different from other treatments for myasthenia gravis?

Iptacopan is unique because it targets a different part of the immune system compared to traditional treatments for myasthenia gravis, which often focus on suppressing the immune response or improving neuromuscular transmission. While specific details about Iptacopan's mechanism in myasthenia gravis are not provided, its novel approach may offer an alternative for patients who do not respond well to existing therapies. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for adults aged 18 to 75 with generalized Myasthenia Gravis (gMG) who are already on a stable standard of care treatment. It's not suitable for those outside this age range or those not following a consistent treatment regimen.

Inclusion Criteria

I am between 18 and 75 years old with generalized Myasthenia Gravis.

My diagnosis of myasthenia gravis (MG) is confirmed by specific tests.

I have been vaccinated against meningitis, pneumonia, and Haemophilus influenzae.

Exclusion Criteria

I have had repeated serious infections.

I recently had treatments like IVIG, PLEX, or specific medications, or a thymectomy.

Pregnant, lactating, intending to become pregnant, or not using effective contraception

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either iptacopan or matching placebo for 6 months while continuing on a stable SOC treatment

6 months

Follow-up

Safety follow-up assessments are performed after the last administration of study treatment

5 weeks

2 visits (in-person)

Open-label extension

Participants receive open-label iptacopan for an additional 24 months

24 months

Treatment Details

Interventions

• Iptacopan

Trial Overview The study tests the effectiveness and safety of Iptacopan, compared to a placebo, in gMG patients. Participants will be randomly assigned to receive either Iptacopan or placebo alongside their regular treatments for six months.

Participant Groups

Group I: Iptacopan Experimental Treatment 1 Intervention

Iptacopan orally for 6 months (double-blind) followed by open-label iptacopan for an additional 24 months

Group II: Matching Placebo Placebo Group 1 Intervention

Placebo orally for 6 months (double-blind) followed by open-label iptacopan for 24 months

Iptacopan is already approved in United States for the following indications:

Approved in United States as Fabhalta for:

• Paroxysmal nocturnal hemoglobinuria (PNH)
• Primary immunoglobulin A nephropathy (IgAN)

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

In a study of 204 patients with ocular myasthenia gravis, early treatment with high-dose intravenous methylprednisolone (IVMP) within 3 months of starting immunotherapy significantly increased the likelihood of achieving minimal manifestations (MM) and minimal manifestations with low prednisolone (MM5mg) status compared to those who did not receive early IVMP.

The early IVMP group not only achieved better clinical outcomes despite having more severe symptoms initially but also required lower doses of oral prednisolone over time, suggesting that early intervention may lead to improved long-term management of ocular MG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Early Treatment with Intravenous High-Dose Methylprednisolone for Ocular Myasthenia Gravis. Uzawa, A., Suzuki, S., Kuwabara, S., et al.[2023]

A single intravenous pulse of methylprednisolone (IVMP) significantly improved muscle function in patients with moderate myasthenia gravis, with an average increase of 27 points compared to only 0.7 points in the placebo group.

The treatment was found to be safe, with no severe side effects reported, and the benefits lasted for an average of 8 weeks, indicating its potential as an effective therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study. Lindberg, C., Andersen, O., Lefvert, AK.[2019]

3,4-diaminopyridine (3,4-DAP) significantly enhances neuromuscular transmission in a mouse model of myasthenia gravis (MG) by increasing the release of acetylcholine, suggesting it could be an effective treatment for patients with MuSK-MG.

The study recommends using low-dose acetylcholinesterase inhibitors to minimize side effects, while proposing that 3,4-DAP may serve as a beneficial symptomatic therapy for improving muscle function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis. Mori, S., Kishi, M., Kubo, S., et al.[2022]

Myasthenia gravis (MG) is a complex autoimmune disease characterized by a defect in neuromuscular transmission, and its treatment can significantly improve daily functions and quality of life, with acetylcholine esterase inhibitors and immunosuppressants like azathioprine being the standard therapies.

New treatment options, including rituximab for severe cases and emerging therapies like belimumab and eculizumab, show promise, although the effectiveness of thymectomy remains uncertain due to a lack of controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myasthenia gravis: an update for the clinician. Sieb, JP.[2022]

Acetylcholinesterase inhibitors are the first-line treatment for all types of myasthenia gravis due to their rapid onset of action, while plasmapheresis and intravenous immunoglobulin (IVIg) are effective for treating exacerbations, typically requiring 3 to 5 sessions for optimal results.

Corticosteroids and immunosuppressive agents are crucial for managing severe cases of myasthenia gravis, with ongoing debates about optimal dosing and duration, highlighting the need for regular treatment adjustments to minimize side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic strategy in myasthenia gravis]. Tranchant, C.[2009]

References

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

Impact of Early Treatment with Intravenous High-Dose Methylprednisolone for Ocular Myasthenia Gravis. [2023]

2. Denmark pubmed.ncbi.nlm.nih.gov

Treatment of myasthenia gravis with methylprednisolone pulse: a double blind study. [2019]

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

3,4-Diaminopyridine improves neuromuscular transmission in a MuSK antibody-induced mouse model of myasthenia gravis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Myasthenia gravis: an update for the clinician. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Therapeutic strategy in myasthenia gravis]. [2009]