BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants Not Receiving Other Complement Inhibitor Therapy (REDEEM-2)

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

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.

Study Overview

• Status: Terminated
• Conditions: Paroxysmal Nocturnal Hemoglobinuria (PNH)
• Intervention / Treatment: Drug: Placebo; Drug: BCX9930 monotherapy

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Daejeon, Korea, Republic of
    • InvestigativeSite
• Malaysia
  • Ampang, Malaysia
    • Investigative Site
• South Africa
  • Bloemfontein, South Africa
    • Investigative Site
  • Cape Town, South Africa
    • Investigative Site
  • Pretoria, South Africa
    • Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: BCX9930 monotherapy; Administered orally twice daily
Placebo Comparator: 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.	Drug: Placebo; Administered orally twice daily; Drug: BCX9930 monotherapy; Administered orally twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Change From Baseline in Hemoglobin at Week 12	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants Who Were Transfusion-free	The number of participants who did not receive any transfusions (packed red blood cells [pRBCs] or whole blood) during the period of interest were reported. Participants who were transfusion free were defined for each treatment group as the number of participants who did not receive any transfusions (pRBCs or whole blood) during the period of interest from the start to the end, inclusive, divided by the total number of participants in that treatment group at the start of the period of interest. Participants who (1) discontinued treatment prior to Week 12, or (2) did not receive a transfusion during the period of interest despite recording a Hemoglobin (Hb) value ≤ 9 g/dL with symptoms assessed by the investigator as warranting transfusion or a Hb value ≤ 7 g/dL regardless of symptoms were not considered 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	The FACIT-Fatigue scale questionnaire was used to determine the level of fatigue experienced by participants. This questionnaire was a 13-item measure that assessed self-reported fatigue and its impact upon daily activities and function. Item scores ranged from 0 ("not at all") to 4 ("very much"), and the total score ranged from 0 to 52, with higher scores indicating greater quality of life.	Baseline, Week 12
Part 1: Percentage (%) Reduction in the Rate of pRBC Units Transfused	The rate of pRBC units transfused from Week 4 to Week 12 was calculated and compared to the rate of pRBC units transfused prestudy during the 12 months prior to screening. The percent reduction in rate of pRBC units transfused was the percent difference in rate relative to the prestudy rate, calculated as: (current rate - prestudy rate)/prestudy rate * 100%. Total rate among all participants was evaluated here. Rate of pRBC units transfusion was defined as the percentage of participants who received pRBC transfusions.	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
Part 1: Number of Participants Achieving Hemoglobin Stabilization	Hemoglobin stabilization was defined as the participants who avoided 2 g/dL or greater decrease in hemoglobin in the absence of transfusion from Week 4 to Week 12.	From Week 4 to Week 12
Part 1: Change From Baseline in Total Paroxysmal Nocturnal Hemoglobinuria (PNH) Red Blood Cell (RBC) Clone Size	The total PNH RBC clone size refers to the percentage of PNH affected (ie, Type 2 and 3) RBC cells within the total RBC population.	Baseline, Week 12
Part 1: Change From Baseline in Ratio of Total PNH RBC Clone Size to PNH White Blood Cell (WBC) Clone Size	The total PNH RBC clone size refers to the percentage of PNH-affected (i.e, Type 2 and 3) RBCs within the total RBC population. The PNH WBC clone size refers to the percentage of PNH-affected WBCs within the total WBC population. The ratio of total PNH RBC clone size to PNH WBC clone size = ratio of percent total PNH RBCs / percent PNH WBCs.	Baseline, Week 12
Part 1: Change From Baseline in Absolute Reticulocyte Count (ARC)		Baseline, Week 12
Part 1: Number of Participants With ARC in the Normal Range	Number of participants with ARC in the normal range (50 - 100 x 10^9 cells/L) were reported.	Week 12
Part 1: Change From Baseline in Haptoglobin		Baseline, Week 12
Part 1: Number of Participants With Haptoglobin ≥ Lower Limit of Normal (LLN) Reference Range	Number of participants with haptoglobin ≥ LLN Reference Range (≥0.3 g/L) were reported.	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

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: David J Kuter, MD, DPhil, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2021
• Primary Completion (Actual): September 18, 2023
• Study Completion (Actual): September 18, 2023

Study Registration Dates

• First Submitted: November 2, 2021
• First Submitted That Met QC Criteria: November 2, 2021
• First Posted (Actual): November 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: paroxysmal nocturnal hemoglobinuria; factor D inhibitor; BCX9930; oral therapy; proximal complement inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urination Disorders; Urological Manifestations; Hematologic Diseases; Bone Marrow Diseases; Anemia, Hemolytic; Anemia; Myelodysplastic Syndromes; Proteinuria; Hemoglobinuria; Hemoglobinuria, Paroxysmal
• Other Study ID Numbers: BCX9930-203; 2020-004403-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No