Clinical Trial Results:
A phase III, multi-center, open label, uncontrolled trial to investigate the efficacy and safety of MK-8962 (corifollitropin alfa) in combination with human Chorionic Gonadotropin (hCG) in inducing increased testicular volume and spermatogenesis in adult men with hypogonadotropic
hypogonadism who remain azoospermic when treated with hCG alone (Phase III; Protocol No. MK-8962-031-00 [also known as SCH 900962, P07937])
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Summary
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EudraCT number |
2012-001258-25 |
Trial protocol |
DE ES IT GB PL Outside EU/EEA |
Global end of trial date |
08 Apr 2015
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Results information
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Results version number |
v2(current) |
This version publication date |
28 Aug 2016
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First version publication date |
20 Apr 2016
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Other versions |
v1 |
Version creation reason |
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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 |
P07937
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01709331 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Merck: MK-8962-031 | ||
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Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000306-PIP01-08 | ||
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 |
08 Apr 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
08 Apr 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
08 Apr 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
This study will assess if corifollitropin alfa (MK-8962), when administered in combination with human chorionic gonadotropin (hCG), will increase testicular volume in men with HH who remain azoospermic after treatment with hCG alone.
Hypothesis: The lower limit of the 95% confidence interval for the geometric mean increase in testicular volume from Day 1 to Week 52 is greater than one.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
14 Feb 2014
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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 |
Australia: 2
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Country: Number of subjects enrolled |
Germany: 2
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Country: Number of subjects enrolled |
Italy: 5
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Country: Number of subjects enrolled |
Poland: 4
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Country: Number of subjects enrolled |
United Kingdom: 4
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Country: Number of subjects enrolled |
Spain: 1
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Worldwide total number of subjects |
18
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EEA total number of subjects |
16
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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) |
18
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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 |
Twenty-three participants entered the 16-week pretreatment phase with hCG. At the end of the pretreatment phase, 18 participants were enrolled in the 52-week combined treatment phase. | ||||||||||
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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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Corifollitropin alfa 150 μg + hCG | ||||||||||
Arm description |
During a 16-week pretreatment phase, participants received twice-weekly subcutaneous (SC) injections of human chorionic gonadotropin (hCG) 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Corifollitropin alfa
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Investigational medicinal product code |
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Other name |
MK-8962
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Corifollitropin alfa 150 μg by SC injection, once every 2 weeks for 52 weeks
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Investigational medicinal product name |
human chorionic gonadotropin (hCG)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solution for solution for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
hCG 1500 or 3000 international units (IU) by SC injection twice a week; administered alone for 16 weeks (pretreatment phase) and then in combination with corifollitropin alfa for 52 weeks (combined treatment phase)
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Baseline characteristics reporting groups
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Reporting group title |
Corifollitropin alfa 150 μg + hCG
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Reporting group description |
During a 16-week pretreatment phase, participants received twice-weekly subcutaneous (SC) injections of human chorionic gonadotropin (hCG) 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase. | |||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Corifollitropin alfa 150 μg + hCG
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.
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Subject analysis set title |
Corifollitropin alfa 150 μg + hCG
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.
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End points reporting groups
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Reporting group title |
Corifollitropin alfa 150 μg + hCG
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Reporting group description |
During a 16-week pretreatment phase, participants received twice-weekly subcutaneous (SC) injections of human chorionic gonadotropin (hCG) 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase. | ||
Subject analysis set title |
Corifollitropin alfa 150 μg + hCG
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.
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Subject analysis set title |
Corifollitropin alfa 150 μg + hCG
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase.
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End point title |
Change from Baseline in Log-Transformed Testicular Volume at Week 52 [1] | ||||||||
End point description |
Participants underwent testicular ultrasound in the pretreatment phase at Weeks -16, -8, -1; and during the combined treatment phase at Baseline (predose, Day 1) and at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52. The testicular volume was measured as the sum of volumes of left and right testes. The mean change from Day 1 in log-transformed testicular volume was analyzed using a mixed model with a fixed effect for time point and a random effect for the participant. For each time point, the mean change from Day 1 to that time point and the associated 95% confidence interval (CI) was calculated. The geometric mean fold change in testicular volume and its 95% CI was obtained by exponentiation. This endpoint was based on the Full Analysis Set (FAS) population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.
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End point type |
Primary
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End point timeframe |
Baseline and Week 52
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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: This was a single-arm study. Therefore no between-group statistical analysis was conducted for the primary end point Fold Change from Baseline in Log-Transformed Testicular Volume at Week 52. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Anti-Corifollitropin Alfa Antibodies [2] | ||||||
End point description |
Blood samples were collected for assessment of anti-corifollitropin alfa antibodies in the pretreatment phase at Week -16 and Week -1; during the combined treatment phase at Weeks 4, 16, 28, 50, and 52; and at the post-treatment follow-up visit, which could occur from Week 53 up to Week 57. This endpoint was based on the All-Subjects-as-Treated (ASaT) population, which consisted of all participants who received any dose of corifollitropin alfa.
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End point type |
Primary
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End point timeframe |
Up to Week 57
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| Notes [2] - 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: This was a single-arm study. Therefore no between-group statistical analysis was conducted for the primary end point Percentage of Participants with Anti-Corifollitropin Alfa Antibodies. |
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| No statistical analyses for this end point | |||||||
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End point title |
Percentage of Participants with Induced Spermatogenesis Resulting in a Sperm Count ≥1x10^6/mL at or before Week 52 | ||||||||
End point description |
Semen samples were produced by masturbation after at least 48 hours of sexual abstinence and collected for evaluation in the pretreatment phase at Week -1, and during the combined treatment phase at Weeks 16, 28, 40, and 52. This endpoint was based on the FAS population, which consisted of all participants who received any dose of corifollitropin alfa and who had a baseline and at least one post-baseline measurement of testicular volume.
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End point type |
Secondary
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End point timeframe |
Up to Week 52
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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 |
Up to 57 weeks
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Adverse event reporting additional description |
The Safety Analysis was based on the ASaT population, which consisted of all participants who received any dose of corifollitropin alfa.
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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 |
18.0
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Reporting groups
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Reporting group title |
Corifollitropin alfa 150 μg + hCG
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Reporting group description |
During a 16-week pretreatment phase, participants received twice-weekly SC injections of hCG 1500 or 3000 IU. Eligible participants were then enrolled in the combined treatment phase in which they received a single dose of corifollitropin alfa 150 μg by SC injection once every 2 weeks for 52 weeks. In addition, eligible participants continued to receive twice-weekly hCG injections on the same schedule begun during the pretreatment phase. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 May 2013 |
The primary reason for the amendment was the addition of text to describe describe the interim analysis (IA) of pharmacokinetic (PK) data after 6 participants completed 6 months of corifollitropin alfa and hCG combined-treatment. The purpose of the IA was to provide data to support preparations for a study in adolescent hypogonadotropic hypogonadism (HH) males (including dose-selection) and development of a PK-model, if necessary, to predict corifollitropin alfa exposure in adolescents. No efficacy or safety analyses were performed in the IA, except that the number of participants with anti-corifollitropin alfa antibodies (Tier-1 Safety Endpoint) was determined. |
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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. | |||
| None reported | |||
