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)

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05162066

Acronym

RENEW

Enrollment

Registered

2021-12-17

Start date

2022-02-18

Completion date

2022-09-23

Last updated

2024-05-02

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, Membranous Nephropathy

Keywords

BCX9930, factor D inhibitor, oral therapy, Complement 3 Glomerulopathy, Immunoglobulin A Nephropathy, Primary Membranous Nephropathy

Brief summary

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

Interventions

DRUGBCX9930

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

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Three parallel treatment cohorts based on diagnosis of C3G, IgAN, or PMN. All eligible participants will receive open-label BCX9930.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percent Change From Baseline in 24-hour uPCR at Week 12	Baseline, 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.
Percent Change From Baseline in 24-hour uPCR at Week 24	Baseline, 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.

Secondary

Measure	Time frame	Description
Number of Participants With a Treatment-emergent Adverse Event (TEAE)	From first dose up to safety follow-up period (Week 28)	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.
Number of Participants Who Discontinued Due to a TEAE	From first dose up to safety follow-up period (Week 28)	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.
Percent Change From Baseline in 24-hour Urinary Protein Excretion	Baseline, Weeks 12, 24,	—
Number of Participants Who Experienced a Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 TEAE	From first dose up to safety follow-up period (Week 28)	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
Number of Participants Who Experienced a CTCAE Treatment-emergent Grade 3 or 4 Laboratory Abnormality	From first dose up to safety follow-up period (Week 28)	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.
Number of Participants Who Experienced a Treatment-emergent Serious Adverse Event (TESAE)	From first dose up to safety follow-up period (Week 28)	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
Change From Baseline in Estimated Glomerular Filtration Rate	Baseline, Weeks 12, 24	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).

Countries

France, Italy, Spain, United Kingdom

Participant flow

Recruitment details

Participants with either complement 3 glomerulopathy (C3G), immunoglobulin A nephropathy (IgAN), or primary membranous nephropathy (PMN) were planned to be enrolled in the study.

Pre-assignment details

At the time the study was discontinued, only participants with historical C3G were enrolled.

Participants by arm

Arm	Count
BCX9930 - C3G Cohort Participants with complement C3G received BCX9930 tablet orally for up to Day 186 (Week 26).	2
BCX9930 - IgAN Cohort Participants with complement IgAN were to receive BCX9930 tablet orally for up to Day 186 (Week 26).	0
BCX9930 - PMN Cohort Participants with complement PMN were to receive BCX9930 tablet orally for up to Day 186 (Week 26).	0
Total	2

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	1	0	0
Overall Study	Perceived lack of efficacy	1	0	0

Baseline characteristics

Characteristic	Total	BCX9930 - C3G Cohort
24-hour Urine Protein-to-creatinine Ratio (uPCR)	380.5 milligram per millimole STANDARD_DEVIATION 137.89	380.5 milligram per millimole STANDARD_DEVIATION 137.89
Age, Continuous	35.5 years STANDARD_DEVIATION 16.26	35.5 years STANDARD_DEVIATION 16.26
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants	0 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants
Race (NIH/OMB) White	2 Participants	2 Participants
Sex: Female, Male Female	1 Participants	1 Participants
Sex: Female, Male Male	1 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 2
other Total, other adverse events	2 / 2
serious Total, serious adverse events	0 / 2

Outcome results

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.

Time frame: Baseline, Week 12

Population: Safety population with available data was analyzed

Arm	Measure	Value (MEAN)
BCX9930	Percent Change From Baseline in 24-hour uPCR at Week 12	-33.2 percent change

Primary

Percent Change From Baseline in 24-hour uPCR at Week 24

Time frame: Baseline, Week 24

Population: Safety population with available data was analyzed

Arm	Measure	Value (MEAN)
BCX9930	Percent Change From Baseline in 24-hour uPCR at Week 24	-8.8 percent change

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).

Time frame: Baseline, Weeks 12, 24

Population: Safety population with available data was analyzed

Arm	Measure	Group	Value (MEAN)
BCX9930	Change From Baseline in Estimated Glomerular Filtration Rate	Change at Week 12	-6.0 mL/min/1.73m^2
BCX9930	Change From Baseline in Estimated Glomerular Filtration Rate	Change at Week 24	-5.0 mL/min/1.73m^2

Secondary