Iptacopan for Vasculitis

Recruiting at 67 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called iptacopan for individuals with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), conditions that inflame blood vessels. The researchers aim to determine if iptacopan, combined with rituximab, can reduce symptoms and maintain remission more effectively than current treatments. The trial also examines the treatment's impact on kidney function and overall quality of life. Suitable candidates for this trial include those recently diagnosed with or experiencing a relapse of GPA or MPA and who have tested positive for certain antibodies. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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

Research has shown that iptacopan has generally been well-tolerated in past studies. Although detailed safety information for humans isn't fully available, ongoing research is examining its use for conditions similar to those in this trial. Iptacopan's presence in a Phase 2 trial indicates it has already demonstrated some safety in earlier testing phases. These earlier trials must have shown that the treatment doesn't pose major safety risks, or it wouldn't have progressed to this stage. However, risks are still under investigation, and this phase will help gather more detailed safety information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Iptacopan is unique because it targets a specific part of the immune system known as the complement pathway, specifically the protein factor B. Most current treatments for vasculitis, like corticosteroids and immunosuppressants, broadly dampen the immune response, which can lead to significant side effects. Iptacopan's targeted action may result in fewer side effects and a more precise treatment for vasculitis. Researchers are excited about the potential for iptacopan to offer a more effective and safer alternative to existing therapies.

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

Research has shown that iptacopan, which participants in this trial may receive, might help manage conditions like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). It affects the complement system, a part of the immune system that can cause inflammation. Studies have found that similar treatments, such as avacopan, effectively reduce disease activity and improve kidney health. This suggests that iptacopan could also reduce symptoms and enhance overall health in people with these conditions. Although more information is needed, early results appear promising. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 (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]

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, 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06388941

Iptacopan in Patients With ANCA Associated Vasculitis 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 ...

2. novartis.com novartis.com/clinicaltrials/study/nct06388941

Iptacopan in Patients With ANCA Associated Vasculitis 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 ...

3. rarediseaseadvisor.com rarediseaseadvisor.com/news/new-study-assess-efficacy-safety-ictacopan-soc-aav/

New Study Will Assess Efficacy and Safety of Iptacopan vs ... A new study will assess the efficacy and safety of iptacopan versus standard of care in patients with ANCA-associated vasculitis (AAV).

4. sciencedirect.com sciencedirect.com/science/article/pii/S2468024925004589

Novel Treatment Paradigms: Complement Inhibition in ... Studies have shown that avacopan can reduce disease activity, proteinuria, and glucocorticoid exposure; and may even allow for greater kidney ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37979959/

Efficacy and safety of avacopan in patients with ANCA- ... Methods: Key efficacy outcomes were remission at week 26 and sustained remission at week 52. Results: Of the 330 patients who received study ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06388941

Iptacopan in Patients With ANCA Associated Vasculitis 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 ...

7. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/528096

Iptacopan in Patients With ANCA Associated Vasculitis The purpose of this study is to evaluate the efficacy and safety of iptacopan compared to standard of care (SOC) to induce and maintain ...

8. trials.arthritis.org trials.arthritis.org/trials/NCT06388941

Iptacopan in Patients With ANCA Associated Vasculitis Study Purpose. 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 ...