Clinical trial NCT05116774: BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants With Inadequate Response to C5 Inhibitor Therapy
Official title: A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal Hemoglobinuria in Subjects With Inadequate Response to C5 Inhibitor Therapy
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
inadequate response to C5 inhibitor
C5 inhibitor
eculizumab
ravulizumab
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 PNH compared to continued C5 inhibitor therapy in adult PNH participants with residual anemia despite treatment with a C5 inhibitor.

Detailed description: This was a randomized, active comparator-controlled, open-label, parallel-group, 2-part study. Parts 1 and 2 were conducted in the same participants.

Part 1 of the study was designed to evaluate the efficacy, safety, and tolerability of oral BCX9930 monotherapy for 24 weeks versus continuing C5 inhibitor therapy in participants with PNH with inadequate response to their current C5 inhibitor therapy. Participants were randomized to either discontinue C5 inhibitor therapy and start BCX9930 monotherapy or to continue C5 inhibitor therapy for the 24-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 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 C5 inhibitor therapy in Part 1 discontinued that therapy at the Week 24 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
* Currently being treated with a stable C5 inhibitor regimen
* Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willing to start vaccination series
* At screening: PNH clone size of ≥ 10% and hemoglobin ≤ 10.5 g/dL

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 24
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Part 1: Number of Participants Who Were Transfusion-free
timeFrame: From Week 4 to Week 24
measure: Part 1: Number of Units of pRBCs Transfused
timeFrame: From Week 4 to Week 24
measure: Part 1: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score
timeFrame: Baseline, Week 24
measure: Part 1: Percent Change From Baseline in Lactate Dehydrogenase
timeFrame: Baseline, Week 24
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 24
measure: Part 1: Number of Participants With Hemoglobin ≥ 12 Grams Per Deciliter (g/dL)
timeFrame: Week 24
measure: Part 1: Number of Participants Who Achieved Hemoglobin Stabilization
timeFrame: From Week 4 to Week 24
measure: Part 1: Change From Baseline in Complement Component 3 (C3)-Opsonized Red Blood Cells (RBCs)
timeFrame: Baseline, Week 24
measure: Part 1: Change From Baseline in Total Paroxysmal Nocturnal Hemoglobinuria (PNH) RBC Clone Size
timeFrame: Baseline, Week 24
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 24
measure: Part 1: Change From Baseline in Absolute Reticulocyte Count (ARC)
timeFrame: Baseline, Week 24
measure: Part 1: Number of Participants With ARC in the Normal Range
timeFrame: Week 24
measure: Part 1: Change From Baseline in Haptoglobin
timeFrame: Baseline, Week 24
measure: Part 1: Number of Participants With Haptoglobin ≥ Lower Limit of Normal (LLN) Reference Range
timeFrame: Week 24
measure: Part 1: Change From Baseline in Total Bilirubin
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Paris
country: France
facility: Investigative Site
city: Budapest
country: Hungary
facility: Investigative Site
city: Rome
country: Italy
facility: Investigative Site
city: Barcelona
country: Spain
facility: Investigative Site
city: Valencia
country: Spain
facility: Investigative Site
city: Leeds
country: United Kingdom
facility: Investigative Site
city: London
country: United Kingdom
facility: Investigative Site
Study officials:
affiliation: King's College Hospital NHS Trust
name: Austin G Kulasekararaj, MBBS, MD
role: PRINCIPAL_INVESTIGATOR
References: