BCX9930 treatment in patients with an inadequate response to C5 inhibitors

• Register: EUCTR
• Last refreshed on: 3 October 2023
• Main ID: EUCTR2020-004438-39-SK
• Date of registration: 29/07/2021
• Prospective Registration: Yes
• Primary sponsor: BioCryst Pharmaceuticals Inc
• Public title: BCX9930 treatment in patients with an inadequate response to C5 inhibitors
• Scientific title: A Randomized, Open-Label, Multicenter, Parallel-Group Study to Evaluate the Efficacy, Safety, and Tolerability of Oral BCX9930 Monotherapy for the Treatment of Paroxysmal Nocturnal Hemoglobinuria in Subjects with Inadequate Response to C5 Inhibitor Therapy - REDEEM 1
• Date of first enrolment: 29/11/2021
• Target sample size: 81
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004438-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Canada, China, Colombia, European Union, France, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Slovakia, Spain, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Project Management
• Affiliation: AMS Advanced Medical Services

• Name: Project Management
• Affiliation: AMS Advanced Medical Services

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, aged = 18 years old.
2. Body weight = 40 kg.
3. Documented diagnosis of PNH confirmed by flow cytometry with a PNH granulocyte or monocyte clone size of = 10% during screening.
4. Treated with a stable regimen of eculizumab for = 3 months prior to the screening visit or ravulizumab for = 6 months prior to the screening visit.
5. Recorded the following results during screening:
a. Hb of = 105 g/L (= 10.5 g/dL).
b. ARC of = 100 × 109 cells/L (= 100,000 cells/µL; = 100 G/L).
c. Absolute neutrophil count of = 0.75 × 109 cells/L (= 750 cells/µL; = 0.75 × G/L).
d. Platelet count of = 30 × 109/L (= 30,000/µL; = 30 G/L).
e. Adequate iron reserve based on ferritin = LLN or total iron binding capacity = upper limit of the normal reference range (ULN).
f. Estimated glomerular filtration rate of = 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Levey and Stevens 2010) and no evidence of clinically relevant abnormal renal function unrelated to underlying PNH disease.
6. Contraception requirements: WOCBP and partners of male subjects to use highly effective contraception
7. Documentation of current vaccinations against Neisseria meningitidis types A, C, W, and Y, and Streptococcus pneumoniae, or willingness to start vaccination series at least 14 days prior to Day 1.
(Note: Vaccination for N. meningitidis type B and for H. influenzae type B (Hib) is strongly encouraged where authorized and available.)
8. In the opinion of the investigator, the subject is expected to adequately comply with all required study procedures and restrictions for the study, including compliance with the twice daily dosing schedule for BCX9930.
9. Willing and able to provide written informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion criteria:
1. Known history of or existing diagnosis of hereditary complement deficiency.
2. History of hematopoietic cell transplant or solid organ transplant or anticipated candidate for transplantation during the study.
3. Myocardial infarction or cerebrovascular accident within 30 days prior to screening, or current and uncontrolled clinically significant cardiovascular or cerebrovascular condition, including unstable angina, severe congestive heart failure, unexplained syncope, arrhythmia, and critical aortic stenosis.
4. History of malignancy within 5 years prior to the screening visit, with exception of adequately treated non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor deemed by the investigator and medical monitor to be at low risk for recurrence.
5. Active bacterial, viral, or fungal infection or any other serious infection within 14 days prior to screening.
(Note: Suspected or confirmed coronavirus disease [COVID-19]; persistent or recurrent positive test(s) for severe acute respiratory syndrome coronavirus 2 [SARS CoV 2] nucleic acids or antigens; and worsening of dyspnea not due to PNH, vasculitic rash, and persistent fever or other symptoms consistent with multisystem inflammatory syndrome in adults [MIS A] are exclusionary.)
6. Current participation in any other investigational drug study or participation in an investigational drug study within 30 days prior to the screening visit, or 5.5 half-lives of the investigational drug, whichever is longer.
7. Treatment with anti-thymocyte globulin within 180 days prior to the screening visit.
8. Initiation of treatment with an erythropoiesis-stimulating agent (eg, erythropoietin), a thrombopoietin receptor agonist (eg, eltrombopag), or danazol within 28 days prior to the screening visit.
(Note: Treatment with these medications initiated > 28 days prior to the screening visit is not exclusionary, if the dose is stable and there is a reasonable expectation that treatment will be continued.)
9. Receiving iron supplementation with an unstable dose in the 28 days prior to the screening visit.
10. Clinically significant abnormal electrocardiogram (ECG) at the screening visit.
(Note: This includes, but is not limited to, a QT interval corrected using Fridericia’s method [QTcF] of > 450 msec in males or > 470 msec in females, or ventricular and/or atrial premature contractions that are more frequent than occasional, and/or as couplets or higher in grouping.)
11. Subjects with any of the following results at the screening visit:
a. Alanine aminotransferase (ALT; also serum glutamic-pyruvic transaminase [SGPT]) > 3 × ULN.
b. Aspartate aminotransferase (AST; also serum glutamic-oxaloacetic transaminase [SGOT]) > 3 × ULN.
(Note: Subjects may be enrolled with AST > 3 × ULN if explained by hemolysis.)
c. Total serum bilirubin > 2 × ULN
(Note: Subjects may be enrolled with total serum bilirubin > 2 × ULN if explained by hemolysis or Gilbert’s syndrome. In the case of hemolysis, total serum bilirubin must be < 5 × ULN and in the case of Gilbert’s syndrome, total serum bilirubin must be < 11 × ULN.)
12. Current use of a prohibited concomitant medication within 7 days prior to Day 1 as detailed in Section 9.8.1.
13. Positive serology for human immunodeficiency virus, or active infection with hepatitis B virus or hepatitis C virus, unless receiving antiviral therapy and viral load is undetectable.
14. Positive drugs o

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Paroxysmal Nocturnal Hemoglobinuria
MedDRA version: 21.1 Level: PT Classification code 10034042 Term: Paroxysmal nocturnal haemoglobinuria System Organ Class: 10038359 - Renal and urinary disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: BCX9930
Product Code: BCX9930
Pharmaceutical Form: Tablet
INN or Proposed INN: BCX9930
Current Sponsor code: BCX9930
Other descriptive name: BCX9930 hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Trade Name: Solaris
Product Name: eculizumab
Product Code: eculizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Eculizumab
CAS Number: 219685-50-4
Current Sponsor code: Soliris
Other descriptive name: Soliris
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Trade Name: Ultomiris
Product Name: Ravulizumab
Product Code: ravulizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RAVULIZUMAB
Current Sponsor code: Ultomiris
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 300-

Product Name: BCX9930
Product Code: BCX9930
Pharmaceutical Form: Tablet
INN or Proposed INN: BCX9930
Current Sponsor code: BCX9930
Other descriptive name: BCX9930 hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Primary Outcome(s)

Primary end point(s): •Change from baseline (CFB) in hemoglobin (Hb)
•Number and proportion of subjects with a TEAE
•Number and proportion of subjects who discontinue due to a TEAE
•Number and proportion of subjects who experience a TESAE
•Number and proportion of subjects who experience a CTCAE Grade 3 or Grade 4 TEAE
•Number and proportion of subjects who experience a treatment-emergent CTCAE Grade 3 or Grade 4 laboratory abnormality

Secondary Objective: •To evaluate the safety and tolerability of BCX9930 monotherapy administered for 24 weeks, as compared to continued C5 inhibitor therapy
•To characterize the effects of BCX9930 monotherapy, as compared to continued C5 inhibitor therapy, using clinical and laboratory measurements, including complement and thrombosis biomarkers, PNH clone size, and C3-opsonization of red blood cells
•To evaluate the effects of BCX9930 monotherapy, as compared to continued C5 inhibitor therapy, on the FACIT-Fatigue scale and other patient-reported outcomes (PROs)
•To assess the effectiveness of BCX9930 monotherapy in the treatment of PNH
•To characterize the effects of BCX9930 monotherapy using clinical and laboratory measurements, including complement and thrombosis biomarkers, PNH clone size, and C3 opsonization of RBCs
•To evaluate the effects of BCX9930 monotherapy on FACIT-Fatigue scale and other PROs
•To characterize BCX9930 PK parameters

Main Objective: •To determine the efficacy of oral BCX9930 monotherapy administered for 24 weeks, compared to continued complement component 5 (C5) inhibitor therapy, in subjects with paroxysmal nocturnal hemoglobinuria (PNH) with an inadequate response to C5 inhibitor therapy
•To evaluate the long-term safety and tolerability of oral BCX9930 monotherapy administered over a 28- to 52 week treatment period in subjects with PNH with an inadequate response to C5 inhibitor therapy

Timepoint(s) of evaluation of this end point: 1 - mean of values at Weeks 12, 16, 20, and 24
others - week 52

Secondary Outcome(s)

Secondary end point(s): 1. Proportion of subjects who are transfusion-free
2. Number of units of packed red blood cells (pRBCs) transfused
3. CFB in FACIT-Fatigue scale score

Timepoint(s) of evaluation of this end point: 1. - week 24
2. - week 24
3. - mean of values at Weeks 12, 16, 20, and 24

Secondary ID(s)

BCX9930-202

2020-004438-39-FR

NCT05116774

Source(s) of Monetary Support

BioCryst Pharmaceuticals Inc

Ethics review

Status: Approved
Approval date: 29/11/2021
Contact: