Danicopan Add-On Therapy for Paroxysmal Nocturnal Hemoglobinuria

Not currently recruiting at 98 trial locations

Overseen By Alexion Pharmaceuticals, Inc.

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Alexion

Must be taking: C5 inhibitors

Disqualifiers: Cardiac, Pulmonary, Renal, Oncologic, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study the long-term effects of danicopan as an add-on treatment for people with Paroxysmal Nocturnal Hemoglobinuria (PNH), a rare blood disease that destroys red blood cells. Participants will continue their existing treatment with danicopan, a new potential drug, alongside a C5 inhibitor, which helps manage PNH symptoms. Those who completed an earlier study using this therapy and have been vaccinated against certain infections may be eligible to join. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the chance to contribute to the potential availability of a new treatment option.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. It seems likely that you can continue your existing treatment with C5i, as danicopan is an add-on therapy.

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

Research has shown that danicopan, when combined with other treatments for paroxysmal nocturnal hemoglobinuria (PNH), is generally safe. Studies have found that danicopan, used alongside medications like ravulizumab or eculizumab, is usually well-tolerated over time. Participants in these studies managed their condition well without major safety issues. While some side effects occurred, they were mostly mild to moderate. This suggests that the treatment is safe for people with PNH, although individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for PNH?

Danicopan is unique because it is an add-on to existing C5 inhibitors, which are the standard treatment for paroxysmal nocturnal hemoglobinuria (PNH). While current therapies primarily block the complement C5 protein to prevent red blood cell destruction, danicopan targets a different part of the complement pathway, specifically the factor D protein. This dual approach can potentially enhance treatment effectiveness, offering better protection against hemolysis and improving patient outcomes. Researchers are excited because this combination could lead to more comprehensive management of PNH symptoms and reduce the need for blood transfusions.

What evidence suggests that danicopan might be an effective treatment for paroxysmal nocturnal hemoglobinuria?

Research has shown that adding danicopan to treatments like ravulizumab or eculizumab effectively manages paroxysmal nocturnal hemoglobinuria (PNH) over time. Studies have found that it helps control a part of the immune system involved in PNH. Long-term evidence supports that danicopan enhances the effectiveness of these treatments by reducing symptoms and the need for blood transfusions. This makes it a promising option for those who still experience symptoms despite current treatments. Participants in this trial will receive danicopan as an add-on therapy to their existing C5 inhibitor treatment. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for people with Paroxysmal Nocturnal Hemoglobinuria (PNH) who have finished a previous Alexion study using Danicopan as an extra treatment. They must be able to consent, follow the study rules, and be vaccinated against Neisseria meningitidis. Those with conditions that could affect the study or pose risks can't join, nor can women who are pregnant, breastfeeding, or planning pregnancy.

Inclusion Criteria

Patient capable of giving signed informed consent, including compliance with the requirements and restrictions listed in the informed consent form and in this protocol

You took part in a previous study sponsored by Alexion that involved using danicopan along with a C5 inhibitor treatment.

I have been vaccinated against Neisseria meningitidis as required.

Exclusion Criteria

Patient permanently discontinued from danicopan in the parent study for any reason other than enrollment into this LTE study

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.

Any medical condition (for example, cardiac, pulmonary, renal, oncologic, or psychiatric) that, in the opinion of the Investigator, might interfere with participation in the study, pose any added risk to the participant, or confound the assessment of the participant

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive danicopan as an add-on to a background C5i therapy, continuing from the parent study

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants continue to receive danicopan as an add-on therapy to C5i for long-term safety and efficacy assessment

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Danicopan

Trial Overview The trial is testing the long-term safety and effectiveness of Danicopan when added to another drug called a C5 inhibitor in patients with PNH. It's a single-arm extension study meaning everyone gets the same treatment without comparison to a placebo or other medication.

How Is the Trial Designed?

Group I: Danicopan Experimental Treatment 1 Intervention

Participants will receive their last dose of danicopan from the parent study the night prior to Day 1 of this LTE study and will continue daily treatment with danicopan together with their background C5i therapy.

Who Is Running the Clinical Trial?

Alexion

Lead Sponsor

Trials

247

Recruited

38,600+

Marc Dunoyer

Alexion

Chief Executive Officer since 2021

PhD in Molecular Biology, University of Brussels

Christophe Hotermans

Alexion

Chief Medical Officer since 2021

MD, University of Leuven

Alexion Pharmaceuticals, Inc.

Lead Sponsor

Trials

267

Recruited

141,000+

Dr. Alberto R. Martinez

Alexion Pharmaceuticals, Inc.

Chief Medical Officer since 2010

MD from University of Sao Paulo

Marc Dunoyer

Alexion Pharmaceuticals, Inc.

Chief Executive Officer since 2021

PhD in Molecular Biology

Alexion Pharmaceuticals

Lead Sponsor

Trials

231

Recruited

36,700+

Marc Dunoyer

Alexion Pharmaceuticals

Chief Executive Officer since 2021

B.A. in Psychology from the University of New Hampshire

Christophe Hotermans

Alexion Pharmaceuticals

Chief Medical Officer since 2023

MD

Published Research Related to This Trial

In a phase 2 study involving 13 patients with paroxysmal nocturnal hemoglobinuria (PNH), iptacopan demonstrated significant efficacy, with 12 out of 12 evaluable patients achieving a reduction in serum lactate dehydrogenase (LDH) levels by at least 60% by week 12, indicating effective control of hemolysis.

Iptacopan was well tolerated with no severe adverse events reported, and most patients experienced clinically meaningful improvements in hemoglobin levels, remaining transfusion-free for up to 12 weeks, showcasing its potential as a safe and effective monotherapy for treatment-naïve PNH patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. Jang, JH., Wong, L., Ko, BS., et al.[2022]

In a phase 2 trial involving 10 untreated patients with paroxysmal nocturnal hemoglobinuria (PNH), danicopan, an oral complement factor D inhibitor, significantly reduced intravascular hemolysis as indicated by a decrease in lactate dehydrogenase (LDH) levels from 5.7 times the upper limit of normal at baseline to 1.8 times at day 28.

The treatment was generally well-tolerated, with only one serious adverse event reported, which resolved without lasting effects, suggesting that danicopan may be a safe option for managing hemolysis in PNH patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria Risitano, AM., Kulasekararaj, AG., Lee, JW., et al.[2021]

In a study of 47 patients with autoimmune hemolytic anemia (AIHA) who had inadequate bone marrow response, treatment with recombinant erythropoietin (rEPO) led to a significant increase in hemoglobin levels, with 91% of patients showing a response by 12 months.

rEPO treatment also reduced the need for blood transfusions from 30% to less than 10% within 15 days, demonstrating its efficacy as an adjunct therapy alongside standard immunosuppressive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis. Fattizzo, B., Pedone, GL., Brambilla, C., et al.[2023]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/8/811/534786/Long-term-efficacy-and-safety-of-danicopan-as-add

Long-term efficacy and safety of danicopan as add-on therapy ... These long-term data demonstrate sustained efficacy and safety of danicopan plus ravulizumab/eculizumab for continued control of terminal ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39700502/

Long-term efficacy and safety of danicopan as add-on ... These long-term data demonstrate sustained efficacy and safety of danicopan plus ravulizumab/eculizumab for continued control of terminal complement activity.

3. icer.org icer.org/wp-content/uploads/2024/03/PNH_Final-Report_For-Publication_03132024.pdf

Iptacopan and Danicopan for Paroxysmal Nocturnal ... Given differences in treatment options and trial designs, we present comparative clinical effectiveness data separately for two related but ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03053102

NCT03053102 | Study of Danicopan in Participants With ... The purpose of this study was to determine the safety and efficacy of ACH-0144471 (also known as danicopan and ALXN2040) in currently untreated participants ...

5. jmcp.org jmcp.org/doi/10.18553/jmcp.2024.30.6.618

Iptacopan and danicopan for paroxysmal nocturnal ... Despite the efficacy of C5 inhibitors, around one-third of treated patients with PNH still have symptomatic anemia, and 20% remain transfusion- ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0165614725001506

Danicopan: complement factor D inhibitor for paroxysmal ... MECHANISM OF ACTION: In paroxysmal nocturnal hemoglobinuria (PNH), somatic mutations lead to clonal blood cell populations lacking GPI-anchored ...