BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants Not Receiving Other Complement Inhibitor Therapy

NCT ID: NCT05116787

Last Updated: 2025-01-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-10-26
• Study Completion Date: 2023-09-18

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.

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

BCX9930 monotherapy

Intervention Type: DRUG

Administered orally twice daily

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Administered orally twice daily

BCX9930 monotherapy

Intervention Type: DRUG

Administered orally twice daily

Interventions

Placebo

Administered orally twice daily

Intervention Type: DRUG

BCX9930 monotherapy

Administered orally twice daily

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BioCryst Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David J Kuter, MD, DPhil

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Investigative Site

Ampang, , Malaysia

Investigative Site

Bloemfontein, , South Africa

Investigative Site

Cape Town, , South Africa

Investigative Site

Pretoria, , South Africa

InvestigativeSite

Daejeon, , South Korea

Countries

Malaysia; South Africa; South Korea

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-004403-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BCX9930-203

Identifier Type: -

Identifier Source: org_study_id