Clinical Trial Results:
A Phase IIA, Open-Label, Single-Arm, Two Stage, Multi-Centre Study to Investigate the Pharmacodynamics, Pharmackinetics, Safety and Tolerability of Repeated Subcutaneous Administration of BIM23B065 in Subjects with Acromegaly
Summary
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EudraCT number |
2015-003868-37 |
Trial protocol |
HU BE BG |
Global end of trial date |
26 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Aug 2018
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First version publication date |
03 Aug 2018
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Other versions |
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 |
D-FR-10380-002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03045302 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Ipsen Pharma SAS
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Sponsor organisation address |
65, quai Georges Gorse, Boulogne-Billancourt, France, 92100
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Public contact |
Medical Director, Ipsen Pharma SAS, clinical.trials@ipsen.com
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Scientific contact |
Medical Director, Ipsen Pharma SAS, clinical.trials@ipsen.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 |
26 May 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
26 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
26 May 2017
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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 assess the pharmacodynamics (PD) of repeated administration of BIM23B065 in reducing growth hormone (GH) in subjects with acromegaly.
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Protection of trial subjects |
The study was conducted under the provision of the Declaration of Helsinki, in accordance with the International Council for Harmonisation Consolidated Guideline on Good Clinical Practice and in compliance with Independent Ethic Committees/Independent Review Boards and informed consent regulations.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Jan 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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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 |
Hungary: 2
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Country: Number of subjects enrolled |
Ukraine: 2
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Worldwide total number of subjects |
4
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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) |
3
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects with acromegaly were recruited from 26 January 2017 in 4 study centres in 4 countries. Stage 1 of the study consisted of a twice daily (BID) regimen of BIM23B065, and a Stage 2 with a three times daily regimen of BIM23B065 was planned but not conducted due to early termination of the study on 26 May 2017. | ||||||||||
Pre-assignment
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Screening details |
7 subjects were screened and 3 failed screening (1 subject did not meet elgibility criteria and 2 subjects did not complete screening procedures due to the early study termination). | ||||||||||
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 | ||||||||||
Arms
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Arm title
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BIM23B065 BID Stage 1 | ||||||||||
Arm description |
Subjects received twice daily administrations of BIM23B065 (at an interval of 12 +/- 1 hour) as subcutaneous injections in the abdominal region during the Stage 1 treatment period which consisted of a titration phase and a treatment phase. Titration phase (Days 1 to 6): Subjects received BIM23B065 0.4 milligram (mg) BID (Days 1 and 2), then BIM23B065 0.6 mg BID (Days 3 and 4) and BIM23B065 0.8 mg BID (Days 5 and 6). Treatment phase (Days 7 to 14): Following titration, a stable target dose of BIM23B065 1.0 mg BID was planned to be administered from Day 7 to Day 14. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
BIM23B065
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received subcutaneous injections BID in the abdominal region administered by a healthcare professional. During the treatment period the possible doses of BIM23B065 (1.0 mg/millilitre [mL]) were: 0.4 mg, 0.6 mg, 0.8 mg up to a target dose of 1.0 mg BID administered as volumes of 0.4 mL, 0.6 mL, 0.8 mL or 1.0 mL respectively.
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Baseline characteristics reporting groups
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Reporting group title |
BIM23B065 BID Stage 1
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Reporting group description |
Subjects received twice daily administrations of BIM23B065 (at an interval of 12 +/- 1 hour) as subcutaneous injections in the abdominal region during the Stage 1 treatment period which consisted of a titration phase and a treatment phase. Titration phase (Days 1 to 6): Subjects received BIM23B065 0.4 milligram (mg) BID (Days 1 and 2), then BIM23B065 0.6 mg BID (Days 3 and 4) and BIM23B065 0.8 mg BID (Days 5 and 6). Treatment phase (Days 7 to 14): Following titration, a stable target dose of BIM23B065 1.0 mg BID was planned to be administered from Day 7 to Day 14. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
BIM23B065 BID Stage 1
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Reporting group description |
Subjects received twice daily administrations of BIM23B065 (at an interval of 12 +/- 1 hour) as subcutaneous injections in the abdominal region during the Stage 1 treatment period which consisted of a titration phase and a treatment phase. Titration phase (Days 1 to 6): Subjects received BIM23B065 0.4 milligram (mg) BID (Days 1 and 2), then BIM23B065 0.6 mg BID (Days 3 and 4) and BIM23B065 0.8 mg BID (Days 5 and 6). Treatment phase (Days 7 to 14): Following titration, a stable target dose of BIM23B065 1.0 mg BID was planned to be administered from Day 7 to Day 14. |
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End point title |
The number of subjects who were GH Responders at Day 14 of the Treatment Period [1] | ||||||
End point description |
A GH responder was defined as a subject with mean serum GH concentration ≤2.5 micrograms per litre (mcg/L) or >50% reduction from mean baseline GH concentration after a 6-day titration and an 8-day treatment period with BIM23B065. The mean serum concentration of GH was measured over 6 hours at baseline (Day -1) and on Day 14. The number of subjects who were GH responders at Day 14 of the treatment period is presented.
The Efficacy Evaluable population consisted of all subjects with at least 1 BIM23B065 administration with available PD data and no protocol deviations with relevant impact on PD data, who had an evaluable primary efficacy endpoint (mean concentration of GH over 6 hours) at baseline and at Day 14.
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End point type |
Primary
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End point timeframe |
From baseline (Day -1) to Day 14.
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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: Data is reported for Stage 1 of the study which was a single reporting group stage and therefore comparative statistical analyses between groups is not applicable. |
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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 |
Treatment emergent adverse events were collected from Day 1 of the treatment period up to the end of the study (up to 4 months).
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Adverse event reporting additional description |
The Safety population consisted of all subjects with at least 1 BIM23B065 administration.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
BIM23B065 BID Stage 1
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Reporting group description |
Subjects received twice daily administrations of BIM23B065 (at an interval of 12 +/- 1 hour) as subcutaneous injections in the abdominal region during the Stage 1 treatment period which consisted of a titration phase and a treatment phase. Titration phase (Days 1 to 6): Subjects received BIM23B065 0.4 mg BID (Days 1 and 2), then BIM23B065 0.6 mg BID (Days 3 and 4) and BIM23B065 0.8 mg BID (Days 5 and 6). Treatment phase (Days 7 to 14): Following titration, a stable target dose of BIM23B065 1.0 mg BID was planned to be administered from Day 7 to Day 14. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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14 Sep 2016 |
- An additional exclusion criterion was added, to exclude subjects with unsubstituted/untreated hypoadrenalism.
- Serum cortisol was added as a safety endocrine parameter.
- The total blood volume was amended in the Blood Sampling Summary.
- The Global Patient Safety contact details were amended. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
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. | |||
The sponsor stopped the study early as the preliminary results in 3 subjects dosed with BIM23B065 showed an inadequate PD profile and efficacy. The enrolled subjects only received BID treatment. Only the primary endpoint results are reported. |