Iptacopan for Vasculitis

Recruiting at 42 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: Rituximab, Glucocorticoids

Disqualifiers: Severe kidney disease, Systemic lupus, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

78 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to standard of care (SOC) to induce and maintain remission in study participants with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), when used in combination with rituximab (RTX) induction. The trial will also assess the impact of iptacopan on disease relapses, evolution of renal function and proteinuria, GC side effects, patients' immune status, and QoL.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is Iptacopan safe for humans?

Iptacopan has been studied in healthy volunteers, and it was primarily eliminated by the liver with no significant safety concerns reported. The study suggests a low risk associated with its metabolites, indicating it is generally safe in humans. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with active granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), who are newly diagnosed or have relapsed. They must need treatment with rituximab and glucocorticoids as per a doctor's judgment, show certain disease severity on a BVAS assessment, and test positive for specific antibodies or have a history of such.

Inclusion Criteria

My condition has been assessed with significant symptoms.

I have tested positive for PR3 or MPO antibodies.

I have been diagnosed with GPA or MPA and need treatment as decided by my doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive iptacopan or placebo in combination with rituximab induction therapy

24 weeks

Regular visits for monitoring and administration

Follow-up

Participants are monitored for safety, effectiveness, and disease relapse

24 weeks

Long-term follow-up

Participants are assessed for sustained remission and long-term effects on renal function and immune status

48 weeks

Treatment Details

Interventions

• Iptacopan

Trial Overview The study tests the effectiveness and safety of iptacopan in combination with rituximab compared to standard care for inducing and maintaining remission in GPA/MPA patients. It will also examine iptacopan's effects on disease relapses, kidney function, side effects from steroids, immune status, and quality of life.

Participant Groups

Group I: Iptacopan Experimental Treatment 2 Interventions

LNP023 administered orally

Group II: Control Placebo Group 2 Interventions

Matching placebo

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

Avacopan demonstrated a remission rate of 65.7% in patients with ANCA-associated vasculitis, significantly higher than the 54.9% remission rate observed in the placebo group during the 52-week ADVOCATE trial.

In the CLEAR trial, avacopan-treated patients showed a greater improvement in the Birmingham Vasculitis Activity Score (≥50% improvement in 86.4% of patients) compared to those treated with prednisone, suggesting avacopan may offer similar or better efficacy with potentially fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. Alihosseini, C., Kopelman, H., Zaino, M., et al.[2023]

Avacopan, recently approved by the FDA, is the first orally bioavailable drug that targets the C5a receptor (C5aR1) and is specifically designed to treat ANCA-associated vasculitis, a rare autoimmune disease.

The drug works by blocking the effects of the C5a peptide, which influences vascular tissue through immune cells, potentially reducing harmful vascular responses and offering a new therapeutic approach compared to traditional treatments focusing on cytokines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

C5a receptor antagonism coming of age for vascular pathology. Marceau, F., Petitclerc, E.[2022]

Iptacopan, a first-in-class oral complement inhibitor, showed a 71% absorption rate in healthy volunteers, with a peak concentration reached in 1.5 hours and a half-life of 12.3 hours, indicating effective systemic availability for therapeutic use.

The drug is primarily eliminated through hepatic metabolism, with the main pathways involving CYP2C8 and UGT1A1, suggesting a low risk associated with its metabolites based on toxicology studies in rats and dogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absorption, Distribution, Metabolism, and Excretion of [14C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies. James, AD., Kulmatycki, K., Poller, B., et al.[2023]

In the ADVOCATE trial involving 331 patients with ANCA-associated vasculitis, avacopan demonstrated noninferiority to prednisone for achieving remission at week 26 and was superior for sustained remission at week 52, suggesting it could be an effective alternative to corticosteroids.

Both treatment groups had similar rates of serious adverse events, indicating that avacopan may offer a safer option for long-term management of ANCA-associated vasculitis without the need for prolonged steroid use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis". Soulsby, WD.[2022]

Avacopan (TAVNEOS™) is a complement 5a receptor antagonist approved in Japan and the USA for treating ANCA-associated vasculitis, specifically microscopic polyangiitis and granulomatosis with polyangiitis, highlighting its efficacy in managing these autoimmune diseases.

While avacopan is effective as an adjunctive treatment, it does not replace glucocorticoids, indicating that it works alongside standard therapies to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avacopan: First Approval. Lee, A.[2022]

References

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

Avacopan for the Treatment of Anti-Neutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

C5a receptor antagonism coming of age for vascular pathology. [2022]

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

Absorption, Distribution, Metabolism, and Excretion of [14C]iptacopan in Healthy Male Volunteers and in In Vivo and In Vitro Studies. [2023]

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

Journal Club Review of "Avacopan for the Treatment of ANCA-Associated Vasculitis". [2022]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Avacopan: First Approval. [2022]