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

Sponsor

BioCryst Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT05116774

Collaborator

(none)

Enrollment

Locations

Arms

21.8

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Dec 6, 2021

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Oct 1, 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 Names: Soliris Drug: Ravulizumab Administered as intravenous infusion per current dose regimen Other Names: Ultomiris, ALXN1210, ravulizumab-cwvz

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 Names:

Soliris

Drug: Ravulizumab

Administered as intravenous infusion per current dose regimen

Other Names:

Ultomiris, ALXN1210, ravulizumab-cwvz

Outcome Measures

Primary Outcome Measures

Change from baseline in hemoglobin [mean of values at Weeks 12, 16, 20, and 24]
Change from baseline in hemoglobin

Secondary Outcome Measures

Proportion of subjects who are transfusion-free [from Day 14 to Week 24]
Proportion of subjects who are transfusion-free
Number of units of packed red blood cells transfused [from Day 14 to Week 24]
Number of units of packed red blood cells transfused
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale score [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Investigative Site	Boston	Massachusetts	United States	02114
2	Investigative Site	Paris		France
3	Investigative Site	Quimper		France
4	Investigative Site	Budapest		Hungary
5	Investigative Site	Barcelona		Spain
6	Investigative Site	Lugo		Spain
7	Investigative Site	Valencia		Spain
8	Investigative Site	Taipei		Taiwan
9	Investigative Site	London		United Kingdom