Phase 3
Completed N=86
Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH)(ALPHA)
Source: ClinicalTrials.gov NCT04469465 ↗Enrolled (actual)
86
Serious AEs
10.9%
Results posted
Jul 2023
Primary outcomePrimary: Change From Baseline in Hgb at Week 12 — 29.40; 4.96; 28.08; 4.62 g/L — p=0.0007
◆ Published Evidence
Established
93citations · ~31 / year
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.
Summary
The main objective of this study is to evaluate the efficacy of danicopan as add-on therapy to a complement component 5 (C5) inhibitor (eculizumab or ravulizumab) in participants with PNH who have clinically evident EVH.
Linked Publications (2)
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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.
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Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVH.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Hgb at Week 12 |
29.40; 4.96; 28.08; 4.62 | 0.0007 sig |
| SECONDARY Percentage of Participants With Hgb Increase of ≥2 Grams/Deciliter (g/dL) (≥20 g/L) From Baseline in the Absence of Transfusion at Week 12 |
59.5; 0; 54.4; 0 | — |
| SECONDARY Percentage of Participants With Transfusion Avoidance Through Week 12 |
83.3; 38.1; 78.9; 27.6 | — |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue Score at Week 12 |
7.97; 1.85; 8.13; 2.35 | — |
| SECONDARY Change From Baseline in Absolute Reticulocyte Count at Week 12 |
-0.0838; 0.0035; -0.0925; -0.0008 | — |
| SECONDARY Change in the Number of Red Blood Cell (RBC) Units Transfused From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment |
-2.7 | — |
| SECONDARY Change in Number of Transfusion Instances From 24 Weeks Prior to Initiation of Treatment to Post 24 Weeks of Treatment |
-1.5 | — |
| SECONDARY Percentage of Participants With Transfusion Avoidance Through Week 24 |
69.1 | — |
| SECONDARY Change in the Number of RBC Units Transfused From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment |
-1.48; -0.18; -1.44; -0.14 | — |
| SECONDARY Change in Number of Transfusion Instances From 12 Weeks Prior to Initiation of Treatment to Post 12 Weeks of Treatment |
-0.92; -0.21; -0.91; -0.11 | — |
| SECONDARY Change From Baseline FACIT Fatigue Scores at Week 24 |
6.21; 5.64 | — |
| SECONDARY Percentage of Participants With Hgb Stabilization During Last 12 Weeks of Treatment in Participants Receiving 24 Weeks of Danicopan |
58.2 | — |
| SECONDARY Percentage of Participants With Hgb Increase of ≥2 g/dL (≥ 20 g/L) From Baseline in the Absence of Transfusion at Week 24 |
41.8 | — |
| SECONDARY Change From Baseline in Total and Direct Bilirubin at Week 12 |
-9.77; -2.15; -2.88; 0.30; -11.55; -1.42 | — |
| SECONDARY Change From Baseline in Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size at Week 12 |
24.60; -3.04; 26.35; -0.18 | — |
| SECONDARY Change From Baseline in Complement Component 3 Fragment Deposition (C3d PNH Type 3 Cells) on PNH RBCs at Week 12 |
-15.06; 0.89; -19.00; 0.68 | — |
| SECONDARY Change From Baseline in Lactate Dehydrogenase at Week 12 |
-23.49; -2.92; -25.60; -16.92 | — |
| SECONDARY Percentage of Participants With Hgb Normalization at Week 12 |
28.6; 0; 26.3; 0 | — |
| SECONDARY Percentage of Participants With Hgb Normalization at Week 24 |
20.0 | — |
Eligibility Criteria
Inclusion Criteria
- Diagnosis of PNH
- 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
- Laboratory abnormalities at screening, including:
- 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)
- Current evidence of biliary cholestasis
- Estimated glomerular filtration rate of <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
Data sourced from ClinicalTrials.gov (NCT04469465) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.