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) (RENEW)

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

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

Study Overview

• Status: Terminated
• Conditions: Immunoglobulin A Nephropathy; Membranous Nephropathy; Complement 3 Glomerulopathy
• Intervention / Treatment: Drug: BCX9930

Detailed Description

This is an open-label, multicenter, proof-of-concept study to evaluate the safety, tolerability, and therapeutic potential of BCX9930 administered for 52 weeks in adult (≥ 18 years old) participants with either C3G, IgAN, or PMN.

All participants will be enrolled into one of the three parallel treatment cohorts based on diagnosis of C3G, IgAN, or PMN and will receive BCX9930 for the 52-week treatment period.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Poitiers, France
    • Investigative Site
  • Toulouse, France
    • Investigative Site
• Italy
  • Bari, Italy
    • Investigative Site
  • Bergamo, Italy
    • Investigative Site
  • Brescia, Italy
    • Investigative Site
  • Turin, Italy
    • Investigative Site
• Spain
  • Barcelona, Spain
    • Investigative Site #1
  • Barcelona, Spain
    • Investigative Site #2
  • Madrid, Spain
    • Investigative Site #1
  • Madrid, Spain
    • Investigative Site #2
• United Kingdom
  • Oxford, United Kingdom
    • Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: C3G cohort; Approximately 14 eligible participants with C3G will be enrolled.	Drug: BCX9930; Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily
Experimental: IgAN cohort; Approximately 14 eligible participants with IgAN will be enrolled.	Drug: BCX9930; Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily
Experimental: PMN cohort; Approximately 14 eligible participants with PMN will be enrolled.	Drug: BCX9930; Administered orally at a dose of 200 mg twice daily for the first 2 weeks, then 400 mg twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in 24-hour Urinary Protein Excretion		Baseline, Weeks 12, 24,
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
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: BioCryst Pharmaceuticals
• Investigators: Principal Investigator: Carla M Nester, MD, MSA, FASN, University of Iowa Stead Family Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2022
• Primary Completion (Actual): September 23, 2022
• Study Completion (Actual): September 23, 2022

Study Registration Dates

• First Submitted: November 26, 2021
• First Submitted That Met QC Criteria: December 16, 2021
• First Posted (Actual): December 17, 2021

Study Record Updates

• Last Update Posted (Estimated): May 2, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: factor D inhibitor; Primary Membranous Nephropathy; BCX9930; oral therapy; Complement 3 Glomerulopathy; Immunoglobulin A Nephropathy
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Nephritis; Glomerulonephritis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Glomerulonephritis, IGA; Glomerulonephritis, Membranous
• Other Study ID Numbers: BCX9930-211; 2020-005855-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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