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: PTClassification code 10034042Term: Paroxysmal nocturnal haemoglobinuriaSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-003829-18-GR
- Lead Sponsor
- Alexion Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- 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.
- At least 1 packed red blood cell or whole blood transfusion within 6 months prior to the start of the study.
• Receiving a C5 inhibitor for at least 6 months prior to Day.
• Platelet count =30,000/microliters (µL)
• Absolute neutrophil counts =750/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 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2
• 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.
• Estimated glomerular filtration rate <30 milliliters/minute/1.73 meter squared and/or are on dialysis.
• Evidence of hepatitis B (positive hepatitis surface antigen [HBsAg] or positive core antibody [anti-HBc] with negative surface antibody [anti-HBs]) or hepatitis C viral infection (HCV antibody positive), except for patients with documented successful treatment and documented sustained virologic response (SVR) at Screening
• Evidence of human immunodeficiency virus (HIV antibody positive) infection at Screening
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Secondary Objective: • 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;Main Objective: To evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor at 12 weeks
- Secondary Outcome Measures
Name Time Method Secondary end point(s): • 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