Danicopan as Add-on Therapy to a C5 Inhibitor in Paroxysmal Nocturnal Hemoglobinuria (PNH) Participants Who Have Clinically Evident Extravascular Hemolysis (EVH) (ALPHA)
- Conditions
- Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Clinically Evident Extravascular Hemolysis (EVH)MedDRA version: 21.1Level: LLTClassification code 10055629Term: Paroxysmal nocturnal hemoglobinuriaSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-003829-18-DE
- Lead Sponsor
- Alexion Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 84
• Diagnosis of PNH
• Clinically evident extravascular hemolysis (EVH) defined by:
- Anemia (Hgb =9.5 gram/deciliter) with absolute reticulocyte count =120 x 10^9/liter.
• Receiving a 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 and prophylactic antibiotics as required.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 59
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 27
• 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, unless the dosage regimen of immunosuppressant has been stable for at least 12 weeks before Day 1 and patient is expected to remain on stable doses through Week 24.
• Known or suspected complement deficiency.
• Laboratory abnormalities at screening, including:
- Alanine aminotransferase >2 x ULN (> 3 x ULN in the case of patients with documented liver iron overload defined by serum ferritin values = 500 ng/mL). The inclusion of patients with documented iron overload and ALT>2 X ULN will be done in a case by case basis, with prior
discussion with the Medical Monitor.
- Direct bilirubin >2 x ULN - patients who, in the opinion of investigator, have direct bilirubin > 2 x ULN due to EVH and/or patients with documented Gilbert's Syndrome. If Gilbert's syndrome is
suspected, the patient will be tested for this condition at screening.
• 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor at 12 weeks;Secondary Objective: • Percentage of patients with Hgb increase = 2g/dl in the absence of transfusion<br>• Percentage Of Participants With Transfusion Avoidance<br>• Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores<br>• Change From Baseline In Absolute Reticulocyte Count;Primary end point(s): • Change From Baseline In Hemoglobin (Hgb);Timepoint(s) of evaluation of this end point: At Week 12
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • Percentage of patients with Hgb increase of = 2g/dl in the absence of transfusion<br>• Percentage Of Participants With Transfusion Avoidance<br>• Change From Baseline In Functional Assessment Of Chronic Illness Therapy (FACIT) Fatigue Scores; Scoring 0-52<br>• Change From Baseline In Absolute Reticulocyte Count;Timepoint(s) of evaluation of this end point: At Week 12<br>