Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)
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| ClinicalTrials.gov Identifier: NCT04469465 |
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Recruitment Status :
Recruiting
First Posted : July 14, 2020
Last Update Posted : April 6, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Paroxysmal Nocturnal Hemoglobinuria | Drug: Danicopan Drug: Placebo Drug: C5 Inhibitor | Phase 3 |
This is a multiple-region, randomized, double-blind, placebo controlled, multiple-dose, study in participants with PNH who have clinically evident EVH on a C5 inhibitor (eculizumab or ravulizumab).
Participants will be randomized to receive danicopan or placebo, in a 2:1 ratio for 12 weeks (Treatment Period 1) in addition to their C5 inhibitor (eculizumab or ravulizumab) therapy. At Week 12, participants randomized to receive placebo will be switched to danicopan in addition to their C5 inhibitor for an additional 12 weeks (Treatment Period 2) and participants randomized to danicopan will continue on danicopan for an additional 12 weeks, while remaining on their ongoing C5 inhibitor therapy.
At the end of the 2 treatment periods (Week 24), participants may enter a Long-Term Extension (LTE) Period and continue to receive danicopan in addition to their C5 inhibitor therapy. The Long-Term Extension period will consist of a first year of LTE(Year1) and a second year of optional LTE(Year2).All patients will complete 72 weeks of LTE(Year 1) assessments. After Week 72 (at the end of the first year of LTE), patients have the choice to complete participation in this study or continue to the optional second year (Year2) of LTE.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 84 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 3 Study of Danicopan (ALXN2040) as Add-on Therapy to a C5 Inhibitor (Eculizumab or Ravulizumab) in Patients With Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH) |
| Actual Study Start Date : | December 16, 2020 |
| Estimated Primary Completion Date : | October 31, 2022 |
| Estimated Study Completion Date : | December 31, 2023 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Danicopan + C5 Inhibitor
Participants will receive danicopan, in addition to their C5 inhibitor therapy, for 24 weeks (12 weeks in Treatment Period 1, followed by 12 weeks in Treatment Period 2).
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Drug: Danicopan
Oral tablet
Other Name: ALXN2040 Drug: C5 Inhibitor Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule. |
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Placebo Comparator: Placebo + C5 Inhibitor
Participants will receive placebo, in addition to their C5 inhibitor therapy, for 12 weeks during Treatment Period 1. At Week 12, participants randomized to receive placebo will be switched to danicopan for an additional 12 weeks (Treatment Period 2).
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Drug: Placebo
Oral tablet Drug: C5 Inhibitor Participants will continue to receive their ongoing C5 inhibitor (eculizumab or ravulizumab) therapy according to their usual dose and schedule. |
- Change From Baseline In Hemoglobin (Hgb) At Week 12 [ Time Frame: Baseline, Week 12 ]
- Percentage of patients with Hgb increase of ≥ 2 g/dL in the absence of transfusion [ Time Frame: Baseline, Week 12 ]
- Percentage Of Participants With Transfusion Avoidance [ Time Frame: Baseline through Week 12 ]
- Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores At Week 12 [ Time Frame: Baseline, Week 12 ]Scoring 0-52
- Change From Baseline In Absolute Reticulocyte Count At Week 12 [ Time Frame: Baseline, Week 12 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosis of PNH
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Clinically Evident EVH defined by:
- Anemia (Hgb ≤9.5 gram/deciliter) with absolute reticulocyte count ≥120 x 10^9/liter
- Receiving an approved C5 inhibitor for at least 6 months prior to Day 1
- Platelet count ≥30,000/microliters (µL)
- Absolute neutrophil counts ≥500/μL
- Documentation of/or willingness to receive vaccinations for N. meningiditis and prophylactic antibiotics as required
Exclusion Criteria:
- History of a major organ transplant or hematopoietic stem cell transplantation (HSCT)
- Participants with known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants
- Known or suspected complement deficiency
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Laboratory abnormalities at screening, including:
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Alanine aminotransferase >2 x ULN (>3 x ULN in case of patients with documented liver iron overload defined by serum ferratin values
- 500 ng/ML)
- Direct bilirubin >2 x ULN (unless due to EVH or documented Gilbert's Syndrome)
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- Current evidence of biliary cholestasis
- Estimated glomerular filtration rate <30 milliliters/minute/1.73 meter squared and/or are on dialysis
- Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C infection at screening
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04469465
| Contact: Alexion Pharmaceuticals Inc. | 855-752-2356 | clinicaltrials@alexion.com |
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| Responsible Party: | Alexion Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT04469465 |
| Other Study ID Numbers: |
ALXN2040-PNH-301 2019-003829-18 ( EudraCT Number ) |
| First Posted: | July 14, 2020 Key Record Dates |
| Last Update Posted: | April 6, 2022 |
| Last Verified: | March 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Paroxysmal Nocturnal Hemoglobinuria (PNH) Extravascular Hemolysis (EVH) Factor D inhibitor |
Complement Danicopan C5 inhibitor |
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Hemoglobinuria Hemoglobinuria, Paroxysmal Hemolysis Proteinuria Urination Disorders Urologic Diseases Urological Manifestations |
Anemia, Hemolytic Anemia Hematologic Diseases Myelodysplastic Syndromes Bone Marrow Diseases Pathologic Processes |