Clinical trial NCT05116787: BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants Not Receiving Other Complement Inhibitor Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
Keywords: BCX9930
factor D inhibitor
proximal complement inhibitor
oral therapy
paroxysmal nocturnal hemoglobinuria
Lead sponsor: BioCryst Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-11-11
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Change From Baseline in Hemoglobin at Week 12
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Part 1: Number of Participants Who Were Transfusion-free
timeFrame: From Week 4 to Week 12
measure: Part 1: Number of Units of pRBCs Transfused
timeFrame: From Week 4 to Week 12
measure: Part 1: Percent Change From Baseline in Lactate Dehydrogenase
timeFrame: Baseline, Week 12
measure: Part 1: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score
timeFrame: Baseline, Week 12
measure: Part 1: Percentage (%) Reduction in the Rate of pRBC Units Transfused
timeFrame: Prestudy (12 months prior to screening) and from Week 4 to Week 12
measure: Part 1: Number of Participants With Hemoglobin ≥ 12 g/dL
timeFrame: At Week 12
measure: Part 1: Number of Participants Achieving Hemoglobin Stabilization
timeFrame: From Week 4 to Week 12
measure: Part 1: Change From Baseline in Total Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size
timeFrame: Baseline, Week 12
measure: Part 1: Change From Baseline in Ratio of Total PNH RBC Clone Size to PNH White Blood Cell (WBC) Clone Size
timeFrame: Baseline, Week 12
measure: Part 1: Change From Baseline in Absolute Reticulocyte Count (ARC)
timeFrame: Baseline, Week 12
measure: Part 1: Number of Participants With ARC in the Normal Range
timeFrame: Week 12
measure: Part 1: Change From Baseline in Haptoglobin
timeFrame: Baseline, Week 12
measure: Part 1: Number of Participants With Haptoglobin ≥ Lower Limit of Normal (LLN) Reference Range
timeFrame: Week 12
measure: Part 1: Change From Baseline in Total Bilirubin
timeFrame: Baseline, Week 12
measure: Part 1: Change From Baseline in Aspartate Aminotransferase (AST)
timeFrame: Baseline, Week 12
Other outcomes:
Locations:
city: Daejeon
country: Korea, Republic of
facility: InvestigativeSite
city: Ampang
country: Malaysia
facility: Investigative Site
city: Bloemfontein
country: South Africa
facility: Investigative Site
city: Cape Town
country: South Africa
facility: Investigative Site
city: Pretoria
country: South Africa
facility: Investigative Site
Study officials:
affiliation: Massachusetts General Hospital
name: David J Kuter, MD, DPhil
role: PRINCIPAL_INVESTIGATOR
References: