A Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal Hemoglobinuria
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- BioCryst Pharmaceuticals
- Enrollment
- 12
- Locations
- 2
- Primary Endpoint
- Part 1: Change From Baseline in Hemoglobin at Week 12
Study Overview
Brief Summary
The purpose of this study was to determine the efficacy and safety of BCX9930 monotherapy for the treatment of adult participants with PNH not currently receiving complement inhibitor therapy.
Detailed Description
This was a randomized, placebo-controlled, double-blind, parallel-group, 2-part study. Parts 1 and 2 was to be conducted in the same participants.
Part 1 of the study was designed to evaluate the efficacy, safety, and tolerability of treatment with oral BCX9930 monotherapy for 12 weeks versus placebo in participants with PNH who were not currently receiving treatment with complement inhibitor therapy. Participants were randomized to receive BCX9930 or placebo under double blind conditions for the 12-week randomized treatment period. The primary efficacy and safety analyses were based on Part 1.
Part 2 of the study was designed to evaluate the long-term safety, tolerability, and effectiveness of open-label BCX9930 monotherapy when administered through Week 52. All participants in Part 2 received BCX9930. Participants who were randomized to BCX9930 monotherapy in Part 1 continued to receive BCX9930 in Part 2. Participants who were randomized to placebo in Part 1 discontinued that therapy at the Week 12 visit and received BCX9930 in Part 2.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female, aged ≥ 18 years old
- •Body weight ≥ 40 kg
- •Documented diagnosis of PNH
- •No complement inhibitor therapy for ≥ 12 months prior to screening
- •Contraindication to or no access to approved (C3 or C5) complement inhibitor therapies
- •Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willingness to start vaccination series
- •At screening: PNH clone of ≥ 10%, hemoglobin ≤ 10.5 g/dL and lactate dehydrogenase ≥ 2 × upper limit of normal
Exclusion Criteria
- •Known history of or existing diagnosis of hereditary complement deficiency
- •History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation
- •Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current and uncontrolled clinically significant cardiovascular or cerebrovascular condition
- •History of malignancy within 5 years prior to the screening visit
- •Active bacterial, viral, or fungal infection or any other serious infection within 14 days prior to screening
- •Treatment with anti-thymocyte globulin within 180 days prior to screening
- •Initiation of treatment with an erythrocyte or platelet growth factor, or danazol within 28 days prior to screening
- •Receiving iron supplementation with an unstable dose in the 28 days prior to screening
Arms & Interventions
BCX9930/BCX9930
Participants received BCX9930 monotherapy in double blind manner (Part 1) for 12 weeks, then in an open-label manner for the remainder of the study (Part 2). After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants on blinded study treatment were switched to open-label BCX9930 prior to Week 12. Initially participants were to receive BCX9930 500 mg twice daily (BID) orally. Per protocol amendment, participants who previously received 500 mg BID and remained on study treatment were dose adjusted to 400 mg BID. For all newly enrolled participants, at the initiation of BCX9930 dosing, participants were administered a dose of 200 mg BID for the first 14 days of treatment before increasing to 400 mg BID. The maximum treatment duration in Part 1 was 12 weeks. The overall maximum duration on BCX9930 was 378 days.
Intervention: BCX9930 monotherapy (Drug)
Placebo/BCX9930
Participants received BCX9930 matching placebo in double blind manner for 12 weeks (Part 1). After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants switched to open-label BCX9930 monotherapy (Part 2) prior to Week 12, if earlier. The maximum duration on Placebo in Part 1 was 12 weeks. The maximum treatment duration on BCX9930 was 281 days.
Intervention: Placebo (Drug)
Placebo/BCX9930
Participants received BCX9930 matching placebo in double blind manner for 12 weeks (Part 1). After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants switched to open-label BCX9930 monotherapy (Part 2) prior to Week 12, if earlier. The maximum duration on Placebo in Part 1 was 12 weeks. The maximum treatment duration on BCX9930 was 281 days.
Intervention: BCX9930 monotherapy (Drug)
Outcomes
Primary Outcomes
Part 1: Change From Baseline in Hemoglobin at Week 12
Time Frame: Baseline, Week 12
Secondary Outcomes
- Part 1: Number of Participants Achieving Hemoglobin Stabilization(From Week 4 to Week 12)
- Part 1: Change From Baseline in Total Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size(Baseline, Week 12)
- Part 1: Change From Baseline in Ratio of Total PNH RBC Clone Size to PNH White Blood Cell (WBC) Clone Size(Baseline, Week 12)
- Part 1: Number of Participants With ARC in the Normal Range(Week 12)
- Part 1: Change From Baseline in Haptoglobin(Baseline, Week 12)
- Part 1: Change From Baseline in Absolute Reticulocyte Count (ARC)(Baseline, Week 12)
- Part 1: Number of Participants With Haptoglobin ≥ Lower Limit of Normal (LLN) Reference Range(Week 12)
- Part 1: Change From Baseline in Total Bilirubin(Baseline, Week 12)
- Part 1: Change From Baseline in Aspartate Aminotransferase (AST)(Baseline, Week 12)
- Part 1: Number of Participants Who Were Transfusion-free(From Week 4 to Week 12)
- Part 1: Number of Units of pRBCs Transfused(From Week 4 to Week 12)
- Part 1: Percent Change From Baseline in Lactate Dehydrogenase(Baseline, Week 12)
- Part 1: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score(Baseline, Week 12)
- Part 1: Percentage (%) Reduction in the Rate of pRBC Units Transfused(Prestudy (12 months prior to screening) and from Week 4 to Week 12)
- Part 1: Number of Participants With Hemoglobin ≥ 12 g/dL(At Week 12)