BCX9930 for Treatment of PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy (REDEEM-1)

A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy

The purpose of this study is to determine the efficacy and safety of BCX9930 monotherapy for the treatment of PNH compared to continued C5 inhibitor therapy in adult PNH patients with residual anemia despite treatment with a C5 inhibitor.

Study Overview

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

Detailed Description

This is a randomized, active comparator-controlled, open-label, parallel-group, 2-part study. Parts 1 and 2 will be conducted in the same subjects.

Part 1 of the study is designed to evaluate the efficacy, safety, and tolerability of oral BCX9930 monotherapy for 24 weeks versus continuing C5 inhibitor therapy in subjects with PNH with inadequate response to their current C5 inhibitor therapy. Subjects will be 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 will be based on Part 1.

Part 2 of the study is designed to evaluate the long-term safety, tolerability, and effectiveness of BCX9930 monotherapy when administered through Week 52. All subjects in Part 2 will receive BCX9930. Subjects who are randomized to BCX9930 monotherapy in Part 1 will continue to receive BCX9930 in Part 2. Subjects who are randomized to C5 inhibitor therapy in Part 1 will discontinue that therapy at the Week 24 visit and receive BCX9930 in Part 2.

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

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Investigative Site
• Hungary
  • Budapest, Hungary
    • Investigative Site
• Italy
  • Rome, Italy
    • Investigative Site
• Spain
  • Barcelona, Spain
    • Investigative Site
  • Valencia, Spain
    • Investigative Site
• United Kingdom
  • Leeds, United Kingdom
    • Investigative Site
  • London, United Kingdom
    • 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
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BCX9930 monotherapy; In Part 1, participants are randomized 2:1 to receive BCX9930 monotherapy or continue with current C5 inhibitor In Part 2, all subjects receive BCX9930 monotherapy	Drug: BCX9930; Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily
Active Comparator: Continued C5 inhibitor therapy; In Part 1, participants are randomized 2:1 to receive BCX9930 monotherapy or continue with current C5 inhibitor	Drug: Eculizumab; Administered by intravenous infusion per current dose regimen; Other Names: Soliris; Drug: Ravulizumab; Administered as intravenous infusion per current dose regimen; Other Names: Ultomiris, ALXN1210, ravulizumab-cwvz

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in hemoglobin	Change from baseline in hemoglobin	mean of values at Weeks 12, 16, 20, and 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects who are transfusion-free	Proportion of subjects who are transfusion-free	from Week 4 to Week 24
Number of units of packed red blood cells transfused	Number of units of packed red blood cells transfused	from Week 4 to Week 24
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale score	Change from baseline in FACIT-Fatigue scale score; FACIT-Fatigue total scale score ranges from 0 to 52, with a higher score indicating less fatigue	mean of values at Weeks 12, 16, 20, and 24

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Austin G Kulasekararaj, MBBS, MD, King's College Hospital NHS Trust

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2021
• Primary Completion (Actual): September 14, 2023
• Study Completion (Actual): September 14, 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): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 22, 2024
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: eculizumab; paroxysmal nocturnal hemoglobinuria; C5 inhibitor; factor D inhibitor; ravulizumab; BCX9930; oral therapy; proximal complement inhibitor; inadequate response to C5 inhibitor
• Additional Relevant MeSH Terms: Urologic Diseases; Urological Manifestations; Bone Marrow Diseases; Hematologic Diseases; Urination Disorders; Anemia; Proteinuria; Anemia, Hemolytic; Myelodysplastic Syndromes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hemoglobinuria; Hemoglobinuria, Paroxysmal; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Eculizumab; Ravulizumab
• Other Study ID Numbers: BCX9930-202; 2020-004438-39 (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
• product manufactured in and exported from the U.S.: Yes