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

• ClinicalTrials.gov Identifier: NCT05116774
• Recruitment Status: Active, not recruiting
• First Posted: November 11, 2021
• Sponsor: BioCryst Pharmaceuticals
• Information provided by (Responsible Party): BioCryst Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria (PNH)	Drug: BCX9930; Drug: Eculizumab; Drug: Ravulizumab	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 81 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 PNH in Subjects With Inadequate Response to C5 Inhibitor Therapy
• Actual Study Start Date: December 6, 2021
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: October 2023

Arms and Interventions

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 500 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 Name: Soliris; Drug: Ravulizumab; Administered as intravenous infusion per current dose regimen; Other Name: Ultomiris, ALXN1210, ravulizumab-cwvz

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in hemoglobin [ Time Frame: mean of values at Weeks 12, 16, 20, and 24 ]
   Change from baseline in hemoglobin

Secondary Outcome Measures :

1. Proportion of subjects who are transfusion-free [ Time Frame: from Day 14 to Week 24 ]
   Proportion of subjects who are transfusion-free
2. Number of units of packed red blood cells transfused [ Time Frame: from Day 14 to Week 24 ]
   Number of units of packed red blood cells transfused
3. Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale score [ Time Frame: mean of values at Weeks 12, 16, 20, and 24 ]
   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

Eligibility Criteria

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

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

Contacts and Locations

Locations

United States, Massachusetts

Investigative Site

Boston, Massachusetts, United States, 02114

France

Investigative Site

Paris, France

Investigative Site

Quimper, France

Hungary

Investigative Site

Budapest, Hungary

Spain

Investigative Site

Barcelona, Spain

Investigative Site

Lugo, Spain

Investigative Site

Valencia, Spain

Taiwan

Investigative Site

Taipei, Taiwan

United Kingdom

Investigative Site

London, United Kingdom

Sponsors and Collaborators

BioCryst Pharmaceuticals

Investigators

• Principal Investigator: Austin G Kulasekararaj, MBBS, MD; King's College Hospital NHS Trust

More Information

• Responsible Party: BioCryst Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05116774
• Other Study ID Numbers: BCX9930-202; 2020-004438-39 ( EudraCT Number )
• First Posted: November 11, 2021
• Last Update Posted: May 9, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by BioCryst Pharmaceuticals:

BCX9930; factor D inhibitor; proximal complement inhibitor; oral therapy; paroxysmal nocturnal hemoglobinuria; inadequate response to C5 inhibitor; C5 inhibitor; eculizumab; ravulizumab

Additional relevant MeSH terms:

Hemoglobinuria; Hemoglobinuria, Paroxysmal; Proteinuria; Urination Disorders; Urologic Diseases; Urological Manifestations; Anemia, Hemolytic; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Eculizumab; Ravulizumab; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs