Clinical Trial Results:
OPuS-4: An open-label study to evaluate the long-term safety of avoralstat in subjects with hereditary angioedema
|
Summary
|
|
EudraCT number |
2015-003242-22 |
Trial protocol |
DE HU BE FR GB IT |
Global end of trial date |
26 Feb 2016
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
24 Mar 2021
|
First version publication date |
24 Mar 2021
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
BCX4161-303
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02670720 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
BioCryst Pharmaceuticals, Inc
|
||
Sponsor organisation address |
4505 Emperor Blvd. Suite 200, Durham, NC, United States, 27703
|
||
Public contact |
Study Director, BioCryst Pharmaceuticals, Inc, 001 919- 859-1302, clinicaltrials@biocryst.com
|
||
Scientific contact |
Study Director, BioCryst Pharmaceuticals, Inc, 001 919- 859-1302, clinicaltrials@biocryst.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
19 Jan 2017
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
26 Feb 2016
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
26 Feb 2016
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To determine the long-term safety and tolerability of oral avoralstat in subjects with hereditary angioedema (HAE)
|
||
Protection of trial subjects |
This trial was conducted in compliance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines for conducting, recording, and reporting trials, and in accordance with the Declaration of Helsinki. The informed consent form (ICF), protocol and amendments for this trial were submitted to and approved by an appropriate Independent Ethics Committee (IEC). Routine monitoring was performed to verify that rights and well-being of subjects were protected. Emergency equipment and medications were available within the clinical unit as per current standard procedures. Any medication considered necessary for the subject’s safety and well-being was given at the discretion of the Investigator. A signed informed consent form (ICF) was obtained from each subject prior to performing any study-related procedures. The informed consent process took place under conditions where the subject had adequate time to consider the risks and benefits associated with his/her participation in the study. The Investigator explained to potential subjects the aims, methods, reasonably anticipated benefits, and potential hazards of the trial and any discomfort it may entail.
|
||
Background therapy |
Subjects used their prescribed standard of care medication to treat any breakthrough HAE attacks on study | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Dec 2015
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Belgium: 2
|
||
Country: Number of subjects enrolled |
France: 4
|
||
Worldwide total number of subjects |
6
|
||
EEA total number of subjects |
6
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
5
|
||
From 65 to 84 years |
1
|
||
85 years and over |
0
|
||
|
|||||||||||||
|
Recruitment
|
|||||||||||||
Recruitment details |
- | ||||||||||||
|
Pre-assignment
|
|||||||||||||
Screening details |
Subjects who completed a previous avoralstat study did not require a Screening Visit if they had interrupted study drug for < 84 days. Avoralstat naïve subjects eligible for the study had a clinical diagnosis of hereditary angioedema (Type I or 2) and were considered a suitable candidate for prophylactic treatment of HAE attacks. | ||||||||||||
|
Period 1
|
|||||||||||||
Period 1 title |
Overall trial (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
|
Arms
|
|||||||||||||
|
Arm title
|
Overall study | ||||||||||||
Arm description |
- | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Avoralstat
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
BCX4161
|
||||||||||||
Pharmaceutical forms |
Capsule, soft
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
5 × 100 mg avoralstat capsules for oral administration 3 times per day (total daily dose of 1500 mg)
|
||||||||||||
|
|||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall trial
|
||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All subjects | ||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Overall study
|
||
Reporting group description |
- | ||
|
|||||||||||||||||||
End point title |
Adverse Events [1] | ||||||||||||||||||
End point description |
Treatment-emergent AEs (TEAEs) were mapped to a Medical Dictionary for Regulatory Activities (MedDRA) preferred term and system organ class. The occurrence of TEAEs was summarized using MedDRA preferred terms, system organ classes, and severity. In addition to severity, AEs and serious AEs (SAEs) were also summarized based on Investigator or Sponsor assessment of relationship to study drug.
|
||||||||||||||||||
End point type |
Primary
|
||||||||||||||||||
End point timeframe |
Planned: 72 weeks. Due to the OPuS-2 study failing to meet its primary endpoint, this study was terminated early. All 6 subjects received treatment for 4 weeks; 3 subjects received treatment for 6 weeks and 1 subject received treatment for 8 weeks
|
||||||||||||||||||
| 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: Primary endpoint was safety and tolerability; no statistical analysis is considered applicable |
|||||||||||||||||||
|
|||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse Events (AEs) reported from informed consent signature until the follow-up visit (2 weeks after last dose IMP) or until the AE is resolved or the subject is in a clinically stable condition with regards to the AE.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Symptoms of HAE were not considered an AE unless they qualify as an SAE.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
18.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Overall study
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
24 Aug 2015 |
• Inclusion criteria were updated to match synopsis.
• Section 11.2.2 (e-Diary) was updated to clarify subject compliance follow-up.
• Section 12.2 (Toxicity Management) was updated to match withdrawal criteria. |
||
07 Dec 2015 |
• Sites in Australia and South America were added.
• Duration of treatment was modified to be up to 72 weeks (originally for as long as patients were deemed to derive clinical benefit). Week 72 Visit assessments were added to the protocol.
• Descriptions of nonclinical toxicology studies were updated.
• A description of the preceding OPuS-2 study was updated.
• The inclusion criterion for women of childbearing potential was updated.
• The inclusion criterion for male subjects regarding contraception was deleted. Recommendations for male subjects were added to Section 11.1 (Investigator-completed Assessments) of the protocol.
• Section 12.2.1 (Management of Pancreatic Dysfunction) was updated to define how HAE attacks should be reported. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Due to the fact that the preceding OPuS-2 study failed to meet its primary endpoint, this study (OPuS-4) was terminated early. Efficacy endpoints and QoL were not analyzed. | |||
