Study to Evaluate the Safety, Tolerability of BCX9930 in Participants With Either Complement 3 Glomerulopathy (C3G), Immunoglobulin A Nephropathy (IgAN), or Primary Membranous Nephropathy (PMN)

Membranous Nephropathy Clinical Trial

— RENEW  

Official title:

An Open-Label, Safety, Tolerability, and Proof-of-Concept Study of Oral BCX9930 Therapy in Subjects With Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, or Primary Membranous Nephropathy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05162066
• Other study ID #: BCX9930-211
• Secondary ID: 2020-005855-19
• Status: Terminated
• Phase: Phase 2
• Start date: February 18, 2022
• Est. completion date: September 23, 2022

Study information

• Verified date: April 2024
• Source: BioCryst Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study was to determine the safety and therapeutic potential of BCX9930 in participants with C3G, IgAN, or PMN.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: September 23, 2022
• Est. primary completion date: September 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Body weight = 40 kilograms (kg)

• Primary diagnosis of C3G, IgAN, or PMN confirmed by central pathology review

• An estimated glomerular filtration rate (eGFR) = 50 milliter per minute per 1.73 meter square (mL/min/1.73 m^2) (or = 30 mL/min/1.73 m^2 after Data Monitoring Committee [DMC] recommendation)

• Receiving treatment with a stable, maximum recommended or maximum tolerated dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for at least 60 days prior to the Day 1 Visit

• Documentation of current vaccinations against Neisseria meningitidis and Streptococcus pneumoniae or willingness to start vaccination series

Exclusion Criteria:

• Known congenital deficiency of C1s, C1r, C1q, C2, or C4

• 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 serious bacterial, viral, or fungal infection or any other serious infection within 14 days of screening

• Treatment with any systemic immunosuppressive or immunomodulatory therapy within 90 days OR anti-CD20 antibody therapies (eg, rituximab) within 180 days prior to the screening visit

• Treatment with renin inhibitors (eg, aliskiren) or sodium-glucose-cotransporter 2 (SGLT2) inhibitors within 60 days prior to Day 1

Related Conditions & MeSH terms

• Complement 3 Glomerulopathy
• Glomerulonephritis, IGA
• Glomerulonephritis, Membranous
• Immunoglobulin A Nephropathy
• Kidney Diseases
• Membranous Nephropathy

Intervention

Drug:
• BCX9930
Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily

Locations

Country	Name	City	State
France	Investigative Site	Poitiers
France	Investigative Site	Toulouse
Italy	Investigative Site	Bari
Italy	Investigative Site	Bergamo
Italy	Investigative Site	Brescia
Italy	Investigative Site	Turin
Spain	Investigative Site #1	Barcelona
Spain	Investigative Site #2	Barcelona
Spain	Investigative Site #1	Madrid
Spain	Investigative Site #2	Madrid
United Kingdom	Investigative Site	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
BioCryst Pharmaceuticals

Countries where clinical trial is conducted

France,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in 24-hour uPCR at Week 12	Urinary protein/creatinine ratio (mg/mmol) =urine protein concentration (mg/dL)/ urine creatinine concentration (mmol/dL). Decrease of urinary protein/creatinine ratio means improvement of renal disease.	Baseline, Week 12
Primary	Percent Change From Baseline in 24-hour uPCR at Week 24	Urinary protein/creatinine ratio (mg/mmol) =urine protein concentration (mg/dL)/ urine creatinine concentration (mmol/dL). Decrease of urinary protein/creatinine ratio means improvement of renal disease.	Baseline, Week 24
Secondary	Percent Change From Baseline in 24-hour Urinary Protein Excretion		Baseline, Weeks 12, 24,
Secondary	Change From Baseline in Estimated Glomerular Filtration Rate	eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula for participants = 18 years old and by the bedside Schwartz formula for participants = 18 years old. eGFR was reported in milliliter per minute per 1.73 per square meter (mL/min/1.73m^2).	Baseline, Weeks 12, 24
Secondary	Number of Participants With a Treatment-emergent Adverse Event (TEAE)	An Adverse event (AE) was any untoward medical occurrence in a clinical study participant. TEAEs were defined, within a dosing group, as AEs that started on or after the first dose of study treatment through 30 days after the last dose of study drug.	From first dose up to safety follow-up period (Week 28)
Secondary	Number of Participants Who Discontinued Due to a TEAE	An AE was any untoward medical occurrence in a clinical study participant. TEAEs were defined, within a dosing group, as AEs that started on or after the first dose of study treatment through 30 days after the last dose of study drug.	From first dose up to safety follow-up period (Week 28)
Secondary	Number of Participants Who Experienced a Treatment-emergent Serious Adverse Event (TESAE)	An AE was any untoward medical occurrence in a clinical study participant. TEAEs were defined, within a dosing group, as AEs that started on or after the first dose of study treatment through 30 days after the last dose of study drug.; A serious adverse event (SAE) was an adverse event/reaction that results in any of the following outcomes: Death; Is life-threatening (participant was at immediate risk of death at the time of the event; it does not refer to an event that hypothetically might have caused death if it were more severe); Requires participant hospitalization (formal admission to a hospital for medical reasons) or prolongation of existing hospitalization; Results in persistent or significant disability/incapacity (ie, there was a substantial disruption of a person's ability to carry out normal life functions); Is a congenital anomaly/birth defect	From first dose up to safety follow-up period (Week 28)
Secondary	Number of Participants Who Experienced a Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 TEAE	An AE was any untoward medical occurrence has no causal relationship with the study drug or with the clinical study itself. It was an unfavorable & unintended sign, symptom, syndrome, or illness that developed or worsened during clinical study.; TEAEs: AEs that started on or after first dose of treatment through 30 days after the last dose of study drug. All AEs were graded using the CTCAE Grades 1 through 5.; Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL); Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Life-threatening consequences; urgent intervention indicated; Grade 5: Death; Participants with Grades 3 or 4 AEs were reported	From first dose up to safety follow-up period (Week 28)
Secondary	Number of Participants Who Experienced a CTCAE Treatment-emergent Grade 3 or 4 Laboratory Abnormality	Treatment-emergent Laboratory Abnormality were defined as an event that started on or after the first dose of study treatment through 30 days after the last dose of study drug.; CTCAE Grades for laboratory abnormalities include: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL.; Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.; Grade 4: Life-threatening consequences; urgent intervention indicated.; Grade 5: Death; Participants with Grades 3 or 4 laboratory abnormality were reported.	From first dose up to safety follow-up period (Week 28)