Clinical Trial Results:
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
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Summary
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EudraCT number |
2020-005855-19 |
Trial protocol |
ES IT HU |
Global end of trial date |
23 Sep 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Oct 2023
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First version publication date |
20 Oct 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
BCX9930-211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05162066 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
BioCryst Pharmaceuticals Inc.
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Sponsor organisation address |
4505 Emperor Blvd., Suite 200, Durham, United States, NC 27703
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Public contact |
Study Director, BioCryst Pharmaceuticals Inc., 001 919859 1302, clinicaltrials@biocryst.com
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Scientific contact |
Study Director, BioCryst Pharmaceuticals Inc., 001 919859 1302, clinicaltrials@biocryst.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
14 Aug 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Sep 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
23 Sep 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the therapeutic potential of BCX9930 as assessed by proteinuria measures
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Protection of trial subjects |
This trial was conducted in compliance with International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines for conducting, recording, and reporting trials, and in accordance with the Declaration of Helsinki.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Nov 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 1
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Country: Number of subjects enrolled |
Italy: 1
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Worldwide total number of subjects |
2
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EEA total number of subjects |
2
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
2
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||
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Pre-assignment
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Screening details |
Subjects with C3G, IgAN, or PMN, who satisfied the protocol inclusion & exclusion criteria during the 56-day screening period, were eligible for the study. The eligibility assessment included confirmation by the central pathologist of a primary diagnosis of either C3G, IgAN, or PMN and active disease, prior to the first dose of BCX9930. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||
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Arms
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Arm title
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Complement 3 Glomerulopathy (C3G) | ||||||||||||
Arm description |
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Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
BCX9930
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects enrolled in the study were treated with BCX9930 provided as 100 mg or 250 mg tablets for oral administration. During the study, a total of 2 subjects received BCX9930. One subject received BCX9930 at 500 mg BID from Day 1 to Day 57. The second subject received BCX9930 at 500 mg BID from Day 1 to Day 104, then 250 mg BID from Day 172 to Day 185, and a single 500 mg dose in the morning of Day 186 before discontinuing treatment.
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Baseline characteristics reporting groups
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Reporting group title |
Complement 3 Glomerulopathy (C3G)
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Complement 3 Glomerulopathy (C3G)
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Reporting group description |
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End point title |
Change in urine protein-to-creatinine ratio (uPCR) from baseline [1] | ||||||||||||||||||||||||||||
End point description |
A 24-hour urine sample was collected at each study visit and analysed for urinary protein and creatinine to establish values for 24-hour urinary protein excretion normalized to urine creatinine (uPCR). Due to early termination of the study, data were collected for only 2 subjects and efficacy analyses was limited to descriptive data for this primary endpoint.
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End point type |
Primary
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End point timeframe |
Samples were collected at baseline, at each visit throughout the 24 weeks BCX9930 treatment and at the end of treatment visit and safety follow-up visit 14 days and 28 days after last dose of BCX9930, respectively.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Due to early termination of the study, data were collected for only 2 subjects and efficacy analyses was limited to descriptive data for this primary endpoint. |
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| Notes [2] - Data at weeks 12, 16, 20 & 24 is for 1 subject only. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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End point title |
Change in eGFR from baseline | ||||||||||||||||||||||||||||
End point description |
A blood sample was collected at each study visit and analysed for serum creatinine which was used to calculate estimated Glomerular Filtration Rate (eGFR) using the CKD-EPI equation. Due to early termination of the study, data were collected for only 2 subjects and efficacy analyses was limited to descriptive data for this secondary endpoint.
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End point type |
Secondary
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End point timeframe |
Samples were collected at baseline, at each visit throughout the 24 weeks BCX9930 treatment and at the end of treatment visit and safety follow-up visit 14 days and 28 days after last dose of BCX9930, respectively.
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| Notes [3] - Data at weeks 12, 16, 20 & 24 is for 1 subject only. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Adverse Events (AEs) were reported from informed consent signature until the final post-treatment follow-up visit (28 days after last dose IMP).
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Adverse event reporting additional description |
If an AE was ongoing at the last follow-up visit, Grade 3 and 4 AEs or AEs deemed possibly, probably, or definitely related to study drug were followed to resolution or until the subject was in a clinically stable condition with regard to the AE.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Complement 3 Glomerulopathy (C3G)
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||||||
Date |
Amendment |
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27 Jan 2022 |
The protocol was amended to:
a) Allow a continuation of BCX9930 treatment for up to 52 weeks for subjects who were assessed, by the treating Investigator, to be receiving clinical benefit.
b) Amend inclusion criteria concerning the definitions of morphological criteria to be determined by central pathology review, for all three indications.
c) Amend exclusion criteria to include budesonide, in line with current marketing authorisations.
d) Amend secondary and exploratory objective descriptions.
e) Include the study termination criteria of “changes in scientific knowledge that lead to negative impact on the risk-benefit profile for subjects".
f) Amend test procedures and statistical analysis in accordance with the 52 week duration of the study. |
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04 Aug 2022 |
As a result of the investigations into elevated serum creatinine in some subjects with Paroxysmal Nocturnal Hemoglobinuria (PNH) treated with BCX9930, the following were amended to reduce the risk of renal events and maintain the risk benefit in favour of the participants:
a) Dosing regimen was amended such that participants were to commence on 200mg BID for 14 days, followed by dose escalation to 400mg BID. This had been lowered from the previous dosing regimen of 500mg BID.
b) Additional monitoring for renal and hepatic events was introduced, with additional safety assessment visits for the first 12 weeks of BCX9930 dosing. The additional visit was once a week for the first 8 weeks, followed by every other week for weeks 8 – 12. The additional safety assessments (3, 5, 6, 7 and 10 weeks post commencement of BCX9930 dosing) could be conducted remotely, using either a local laboratory service, or a home health service, to reduce the inconvenience for participants.
c) Participant discontinuation and study discontinuation criteria were amended in regard to treatment emergent changes in serum creatinine levels.
d) To reduce the burden on participants, the kidney biopsy requirements at study entry were broadened to allow historical biopsies. The second kidney biopsy was made optional for IgAN and PMN participants.
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| In December 2022, BioCryst stopped development of BCX9930 based on changes in the competitive environment. Therefore, this study was prematurely discontinued. A total of 3 subjects were screened and 2 subjects were administered BCX9930. | |||||||
