Iptacopan for Myasthenia Gravis

Recruiting at 96 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment, iptacopan, can help individuals with generalized Myasthenia Gravis (gMG), a condition that causes muscle weakness. Participants will receive either iptacopan or a placebo (a look-alike pill with no active medicine) for six months while continuing their usual treatment. The study seeks individuals with gMG who have tested positive for a specific antibody (AChR+) and have tried other treatments but still struggle with symptoms. Eligible participants will continue on open-label iptacopan for an additional 24 months after the initial trial period. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Research has shown that iptacopan is generally safe and well-tolerated. Previous studies reported no deaths or serious side effects linked to the treatment. Participants also did not experience any bacterial infections. This evidence suggests that the treatment is safe for humans, which may reassure those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myasthenia gravis?

Unlike the standard treatments for myasthenia gravis, which often include medications like corticosteroids and immunosuppressants, iptacopan offers a fresh approach by targeting the complement system, a part of the immune system. Most treatments work by broadly suppressing the immune response, but iptacopan specifically inhibits a protein involved in the complement pathway, potentially reducing side effects associated with generalized immune suppression. Researchers are excited about iptacopan because it could provide more precise control over the disease, leading to fewer symptoms and improved quality of life for patients.

What evidence suggests that iptacopan might be an effective treatment for myasthenia gravis?

Research shows that iptacopan might help treat myasthenia gravis, a condition that causes muscle weakness. In this trial, participants will receive either iptacopan or a matching placebo for 6 months in a double-blind phase. Previous studies have shown that patients taking iptacopan performed daily tasks more easily, as indicated by improved Myasthenia Gravis Activity of Daily Living (MG-ADL) scores. Iptacopan blocks a part of the immune system involved in the disease. Studies have found it to be safe, with no serious side effects reported. This suggests iptacopan could help people manage their symptoms better. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

Citations

1. neurology.org neurology.org/doi/10.1212/WNL.0000000000211246

Efficacy and Safety of Iptacopan in Patients with ... The primary endpoint is the change in Myasthenia Gravis Activity of Daily Living (MG-ADL) score from baseline to Month 6. Key secondary ...

2. novartis.com novartis.com/clinicaltrials/study/nct06517758

A Phase III Study to Investigate Efficacy, Safety and ... The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06517758

NCT06517758 | A Phase III Study to Investigate Efficacy, ... The study is a randomized, double-blind, placebo-controlled, multicenter, Phase III study, to evaluate efficacy, safety and tolerability of iptacopan in ...

4. neurologylive.com neurologylive.com/view/new-study-assess-complement-inhibitor-iptacopan-generalized-myasthenia-gravis

New Study to Assess Complement Inhibitor Iptacopan in ... All told, results showed that iptacopan was well-tolerated, with no reports of deaths, treatment-related serious adverse events or bacterial ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37914086/

Results of a randomized double-blind placebo-controlled ... Iptacopan was well-tolerated, with no reports of deaths, treatment-related serious adverse events or bacterial infections, and led to strong ...