IRB Study Number FLA21-051
Status Recruiting
Phase Phase 3
Institute Taussig Cancer Institute
Description
Primary Objective
• To evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor at 12 weeks
Secondary Objectives
• To evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor on transfusion avoidance at 12 weeks
• To evaluate the effect of danicopan as compared to placebo as add-on therapy to a C5 inhibitor on Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scores for 12 weeks of treatment
• To evaluate the effect of danicopan as compared to placebo as add-on therapy to a C5 inhibitor on absolute reticulocyte count
• To evaluate the efficacy of danicopan as add-on therapy to a C5 inhibitor on transfusion requirements at 24 weeks for those patients receiving 24 weeks of danicopan
• To evaluate the efficacy of danicopan as compared to placebo as add-on therapy to a C5 inhibitor on transfusion requirements at 12 weeks
• To evaluate the effect of danicopan as add-on therapy to a C5 inhibitor on Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scores for 24 weeks of treatment
• To assess the efficacy of danicopan as add-on therapy to a C5 inhibitor on hemoglobin stabilization
• To assess additional laboratory markers relevant in PNH patients
Inclusion Criteria
Diagnosis of PNH.
Clinically Evident Extravascular hemolysis (EVH) defined by:
• Anemia (Hgb ≤ 9.5 g/dL) with absolute reticulocyte count ≥ 120 × 109/L.
• At least 1 packed red blood cells (pRBCs) or whole blood transfusion within 6 months prior to the start of the study
Receiving an approved C5 inhibitor for at least 6 months prior to Day 1 in this study at an approved dose (or higher) and with no change in dose or interval for at least 24 weeks preceding Day 1. For those patients who recently switched from eculizumab to ravulizumab, they must have received at least the loading dose and 3 maintenance doses (minimum of 24 weeks) of ravulizumab preceding Day 1.
Platelet count ≥ 30,000/μL without the need for platelet transfusions.
Absolute neutrophil counts (ANC) ≥ 750/μL.
Documentation of vaccination for N. meningitidis: All patients must be vaccinated against meningococcal infections within 3 years prior to, or at the time of initiating study drug. Patients who initiate study drug treatment less than 2 weeks after receiving a meningococcal vaccine must receive treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination.
Age 18 years or older (or greater than or equal to minimum adult age in accordance with local legal requirements).
Female patients of childbearing potential must agree to use a highly effective or acceptable method of contraception from the date of signing the informed consent until the specified duration after the last dose of their background C5 inhibitor as per the product labelling. Female patients of childbearing potential must also have a negative serum pregnancy test during Screening and negative urine pregnancy test on Day 1.
Female patients with documented evidence of non-childbearing potential need not employ a method of contraception.
Nonsterile male patients must agree to use a highly effective or acceptable method of contraception with their partner(s) of childbearing potential from the first day of dosing to 90 days after their last dose of study drug.
• Males who are surgically sterile need not employ additional contraception.
• Males must agree not to donate sperm while enrolled in this study and for 90 days after their last dose of study drug.
Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Must have access to emergency medical care.
Patients who are on iron, folic acid, and vitamin B12 supplementation are eligible for the study if on a stable dose for at least 30 days prior to Day 1. See Section 6.5.
Exclusion Criteria
History of a major organ transplant (e.g., heart, lung, kidney, liver) or HSCT.
Known aplastic anemia or other bone marrow failure that requires HSCT or other therapies including anti-thymocyte globulin and/or immunosuppressants
Received another investigational agent other than C5 inhibitors (eculizumab or ravulizumab) within 30 days or 5 half-lives of the investigational agent prior to study entry, whichever is greater.
Known or suspected complement deficiency.
Known underlying bleeding disorders (eg, coagulation factor deficiencies, idiopathic thrombocytopenic purpura, Von Willebrand disease, etc.) or any conditions leading to anemia that are not primarily due to PNH.
Active bacterial or viral infection, a body temperature >38°C on two consecutive daily measures, evidence of other infection, or history of any febrile illness within 14 days prior to first study drug administration.
History or presence of any clinically relevant co-morbidities that would make the patient inappropriate for the study (eg, is likely to result in deterioration of the patient’s condition, affect the patient’s safety during the study, or confound the results of the study).
Laboratory abnormalities at screening, including:
• ALT > 2 × ULN
• Direct bilirubin > 2 × ULN (unless due to extravascular hemolysis, in the opinion of the Investigator) and patients with Gilbert’s Syndrome will be allowed into this study; however, documentation of Gilbert’s Syndrome is required. If increased bilirubin is suggestive of Gilbert's syndrome, but the patient cannot provide documentation; then, the patient will be tested for this condition. See Section 8.4.1 for details.
Any other clinically significant laboratory abnormality as judged by the Investigator that, in the opinion of the Principal Investigator, would make the patient inappropriate for the study or put the patient at undue risk.
Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of study drug administration.
Current evidence of biliary cholestasis.
Evidence of human immunodeficiency virus, hepatitis B, or active hepatitis C infection at screening.
Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and/or are on dialysis.
Hypersensitivity to the investigational drug (danicopan) or any of its excipients
