Danicopan Add-On Therapy for Paroxysmal Nocturnal Hemoglobinuria

Recruiting at 87 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

80 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Danicopan for treating paroxysmal nocturnal hemoglobinuria?

In a study, patients with paroxysmal nocturnal hemoglobinuria who were already on eculizumab and received Danicopan showed a significant increase in hemoglobin levels and a reduction in the need for blood transfusions. This suggests that Danicopan can help improve blood health and reduce symptoms in these patients. ^{1 2 3 4 5}

How does the drug Danicopan differ from other treatments for paroxysmal nocturnal hemoglobinuria?

Danicopan is unique because it is an oral drug that specifically inhibits complement factor D, a part of the immune system that contributes to the destruction of red blood cells in paroxysmal nocturnal hemoglobinuria (PNH). This approach helps control both intravascular and extravascular hemolysis, offering a novel mechanism compared to existing treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

This is a single-arm long-term extension study that will enroll participants with PNH who have completed participation in Alexion-sponsored clinical studies with danicopan as an add on therapy to a C5i.

Eligibility Criteria

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

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

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

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

Phase 2 study of danicopan in patients with paroxysmal nocturnal hemoglobinuria with an inadequate response to eculizumab. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial. [2023]

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

Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Ex vivo expansion of CD34(+) CD59(+) cells from bone marrow of paroxysmal nocturnal hemoglobinuria patients]. [2017]

5. Japan pubmed.ncbi.nlm.nih.gov

Danazol treatment for paroxysmal nocturnal hemoglobinuria. [2019]

6. Italy pubmed.ncbi.nlm.nih.gov

Danicopan: an oral complement factor D inhibitor for paroxysmal nocturnal hemoglobinuria [2021]

7. England pubmed.ncbi.nlm.nih.gov

Fetal haemoglobin augmentation in E/beta(0) thalassaemia: clinical and haematological outcome. [2013]

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

Hydroxyurea induction of fetal hemoglobin synthesis in sickle-cell disease. [2018]

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

Recombinant erythropoietin in autoimmune hemolytic anemia with inadequate bone marrow response: a prospective analysis. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of riboflavin treatment on human red cell pyruvate kinase deficiency. [2019]