BCX9930 for the Treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in Participants With Inadequate Response to C5 Inhibitor Therapy

NCT05116774 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: BCX9930-2022020-004438-39
• Study Type: interventional
• Target: 12
• Locations: 5 countries
• Sites: 7

Brief Summary

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

Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Part 1: Change From Baseline in Hemoglobin at Week 24

  Baseline, Week 24

Secondary Outcomes (15)

• Part 1: Number of Participants Who Were Transfusion-free

  From Week 4 to Week 24

• Part 1: Number of Units of pRBCs Transfused

  From Week 4 to Week 24

• Part 1: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Score

  Baseline, Week 24

• Part 1: Percent Change From Baseline in Lactate Dehydrogenase

  Baseline, Week 24

• Part 1: Percentage (%) Reduction in the Rate of pRBC Units Transfused

  Prestudy (12 months prior to screening) and from Week 4 to Week 24

Study Arms (2)

BCX9930/BCX9930

EXPERIMENTAL

Participants were randomized to receive BCX9930 during Part 1 and continued to receive the same during Part 2. Per protocol amendment, participants who previously received 500 mg twice daily (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 on BCX9930 in Part 1 was 24 weeks. The overall maximum treatment duration on BCX9930 was 377 days.

Drug: BCX9930

C5-Inhibitor (C5-INH)/BCX9930

ACTIVE COMPARATOR

Participants randomized to this group continued the existing C5-INH therapy during Part 1. After the sponsor decided to halt enrolment in the study permanently and terminate the study, participants entered Part 2 where they switched to open-label BCX9930 monotherapy prior to Week 24, if earlier. The maximum treatment duration on C5-INH in Part 1 was 24 weeks. The maximum treatment duration on BCX9930 was 197 days.

Drug: Eculizumab; Drug: Ravulizumab; Drug: BCX9930

Interventions

Eculizumab DRUG

Administered by intravenous infusion per current dose regimen

Also known as: Soliris

C5-Inhibitor (C5-INH)/BCX9930

Ravulizumab DRUG

Administered by intravenous infusion per current dose regimen

Also known as: Ultomiris, ALXN1210, ravulizumab-cwvz

C5-Inhibitor (C5-INH)/BCX9930

BCX9930 DRUG

Administered orally twice daily

BCX9930/BCX9930; C5-Inhibitor (C5-INH)/BCX9930

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• BioCryst Pharmaceuticals: lead

Study Sites (7)

Investigative Site

Paris, France

Location

Investigative Site

Budapest, Hungary

Location

Investigative Site

Rome, Italy

Location

Investigative Site

Barcelona, Spain

Location

Investigative Site

Valencia, Spain

Location

Investigative Site

Leeds, United Kingdom

Location

Investigative Site

London, United Kingdom

Location

MeSH Terms

Conditions

Hemoglobinuria, Paroxysmal

Interventions

eculizumab; ravulizumab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Limitations and Caveats

The sponsor decided to terminate the development program (including this study).

Results Point of Contact

• Title: Study Director
• Organization: BioCryst Pharmaceuticals Inc

clinicaltrials@biocryst.com

+1 919-859-1302

Study Officials

• Austin G Kulasekararaj, MBBS, MD

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 11, 2021
• Study Start: December 6, 2021
• Primary Completion: September 14, 2023
• Study Completion: September 14, 2023
• Last Updated: March 7, 2025
• Results First Posted: March 7, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); HU (1); GB (2); ES (2); FR (1)