Clinical Trial Results:
A controlled, assessor-blind, parallel groups, multicentre, multinational trial evaluating the immunogenicity of FE 999049 in repeated cycles of controlled ovarian stimulation in women undergoing an assisted reproductive technology programme
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Summary
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EudraCT number |
2013-001616-30 |
Trial protocol |
BE GB CZ DK ES PL IT |
Global end of trial date |
03 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
04 May 2017
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First version publication date |
04 May 2017
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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 |
000071
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01956123 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Ferring Pharmaceuticals A/S
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Sponsor organisation address |
Kay Fiskers Plads 11, Copenhagen S, Denmark, 2300
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Public contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.com
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Scientific contact |
Clinical Development Support, Ferring Pharmaceuticals, DK0-Disclosure@ferring.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 Jan 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 May 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
03 Jan 2017
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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 |
To evaluate the immunogenicity of FE 999049 and GONAL-F based on the presence of anti-follicle-stimulating hormone (FSH) antibodies and their neutralising capacity in women undergoing repeated controlled ovarian stimulation (COS) cycles.
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Protection of trial subjects |
The trial was performed in accordance with the Declaration of Helsinki and its amendments in force at the initiation of the trial.
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Background therapy |
As concomitant therapy in the COS cycle, CETROTIDE (gonadotropin releasing hormone [GnRH] antagonist), OVITRELLE (human chorionic gonadotropin [hCG]), GONAPEPTYL (GnRH agonist), and ENDOMETRIN (progesterone) were used as non-investigational medicinal products (NIMPs). All NIMPs were used in line with the recommendations in the respective products’ labelling for the indication of assisted reproductive technologies (ART) and/or standard clinical practice and supported by literature. | ||
Evidence for comparator |
This was a controlled trial evaluating the immunogenicity of FE 999049 during repeated exposure. GONAL-F was included as a reference group. GONAL-F is a commercially available recombinant follicle stimulating hormone (rFSH) preparation. | ||
Actual start date of recruitment |
26 Mar 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 |
Brazil: 22
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Country: Number of subjects enrolled |
Canada: 75
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Country: Number of subjects enrolled |
Russian Federation: 17
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Country: Number of subjects enrolled |
Poland: 49
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Country: Number of subjects enrolled |
Spain: 201
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Country: Number of subjects enrolled |
United Kingdom: 16
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Country: Number of subjects enrolled |
Belgium: 15
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Country: Number of subjects enrolled |
Czech Republic: 63
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Country: Number of subjects enrolled |
Denmark: 37
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Country: Number of subjects enrolled |
Italy: 18
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Worldwide total number of subjects |
513
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EEA total number of subjects |
399
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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) |
513
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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 |
A total of 32 investigational sites included subjects to the trial : 3 in Belgium, 3 in Brazil, 3 in Canada, 3 in the Czech Republic, 2 in Denmark, 2 in Italy, 2 in Poland, 2 in Russia, 10 in Spain and 2 in United Kingdom. | ||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects who participated in Trial 000004 (COS cycle 1) and failed to achieve an ongoing pregnancy were eligible for the trial. For COS cycle 2, 520 subjects were screened, of whom 513 subjects were enrolled. For COS cycle 3, 190 subjects were screened, of whom 189 subjects were enrolled (1 subject was an enrolment failure and never exposed to IMP) | ||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial Period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Single blind | ||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Assessor [1] | ||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
The trial was assessor-blind and all investigators, embryologists and central laboratory personnel were blinded to treatment allocation throughout the trial. The trial medication delegate at site (person responsible for investigational medicinal product [IMP]/NIMP), the trial coordinator at site (person entering data into e-CRF), the monitors and the participating subjects knew the treatment allocation. Ferring clinical trial team was blinded to treatment allocation until breaking of the blind.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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FE 999049 (COS cycle 2) | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
FE 999049
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Investigational medicinal product code |
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Other name |
Follitropin delta
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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 |
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 1. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 18 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days.
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Arm title
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GONAL-F (COS cycle 2) | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
GONAL-F
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Investigational medicinal product code |
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Other name |
Follitropin alfa
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose was determined based on the ovarian response in COS cycle 1. The GONAL-F starting dose was fixed for the first 5 days after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days.
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Arm title
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FE 999049 (COS cycle 3) | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
FE 999049
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Investigational medicinal product code |
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Other name |
Follitropin delta
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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 |
FE 999049 was administered as single daily subcutaneous injections in the abdomen. The dose was determined based on the ovarian response in COS cycle 2. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 24 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days.
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Arm title
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GONAL-F (COS cycle 3) | ||||||||||||||||||||||||||||||||||||||||
Arm description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
GONAL-F
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Investigational medicinal product code |
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Other name |
Follitropin alfa
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Pharmaceutical forms |
Solution for injection in pre-filled pen
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose was determined based on the ovarian response in COS cycle 2. The GONAL-F starting dose was fixed for the first 5 days after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days.
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| Notes [1] - The roles blinded appear inconsistent with a simple blinded trial. Justification: Due to differences in formulation and packaging of the two IMPs, subject blinding was not feasible. |
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Baseline characteristics reporting groups
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Reporting group title |
FE 999049 (COS cycle 2)
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Reporting group description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GONAL-F (COS cycle 2)
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Reporting group description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FE 999049 (COS cycle 3)
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Reporting group description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GONAL-F (COS cycle 3)
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Reporting group description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
FE 999049 (COS cycle 2)
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Reporting group description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||
Reporting group title |
GONAL-F (COS cycle 2)
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Reporting group description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||
Reporting group title |
FE 999049 (COS cycle 3)
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Reporting group description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||
Reporting group title |
GONAL-F (COS cycle 3)
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Reporting group description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||
Subject analysis set title |
Modified intention-to-treat (mITT) analysis set
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
The mITT analysis set was defined as all exposed subjects. Subjects were analysed according to actual treatment received.
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Subject analysis set title |
Safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety analysis set was defined as all exposed subjects. Subjects were analysed according to actual treatment received. The safety analysis set was identical to the mITT analysis set.
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End point title |
Proportion of subjects with treatment-induced anti-FSH antibodies after up to two repeated COS cycles [1] [2] | ||||||||||||
End point description |
The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point is presented for the safety analysis set.
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End point type |
Primary
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End point timeframe |
Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
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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: Descriptive statistics was used to present this endpoint. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The cumulative incidences in COS cycle 2 and COS cycle 3 divided by subjects in COS cycle 2 are presented. Subjects with observations in both cycles are only counted once. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Proportion of subjects with treatment-induced anti-FSH antibodies with neutralising capacity after up to two repeated COS cycles [3] | ||||||||||||
End point description |
The proportion of subjects with treatment-induced anti-FSH antibodies with neutralising capacity at any time point is presented for the safety analysis set.
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End point type |
Secondary
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End point timeframe |
Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
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| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The cumulative incidences in COS cycle 2 and COS cycle 3 divided by subjects in COS cycle 2 are presented. Subjects with observations in both cycles are only counted once. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number and size of follicles on stimulation day 6 and end-of stimulation for each COS cycle | ||||||||||||||||||||||||||||||
End point description |
Total number of follicles with size >= 12 mm on stimulation day 6 and at end-of-stimulation are presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
Stimulation day 6 and end-of stimulation
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Proportion of subjects with extreme ovarian responses for each COS cycle | ||||||||||||||||||||||||||||||
End point description |
Extreme ovarian response was defined as <4, ≥15 or ≥20 oocytes retrieved. Data are presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
Oocyte retrieval visit (36 hr [±2 hr] after triggering of final follicular maturation)
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| Notes [4] - Subjects who underwent triggering of final follicular maturation. [5] - Subjects who underwent triggering of final follicular maturation. [6] - Subjects who underwent triggering of final follicular maturation. [7] - Subjects who underwent triggering of final follicular maturation. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Proportion of subjects with early OHSS and/or preventive interventions for early OHSS for each COS cycle | |||||||||||||||||||||||||||||||||||||||||||||
End point description |
The proportion of subjects with early ovarian hyperstimulation syndrome (OHSS), early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
9 days after triggering of final follicular maturation
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response for each COS cycle | |||||||||||||||||||||||||||||||||||
End point description |
Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with GnRH agonist are presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
End-of-stimulation
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||||
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End point title |
Metaphase II oocytes (inseminated through ICSI) for each COS cycle | ||||||||||||||||||||
End point description |
Number of oocytes in metaphase II prior to intracytoplasmic sperm injection (ICSI) insemination is presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
Prior to insemination
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| Notes [8] - Subjects with all oocytes inseminated using ICSI. [9] - Subjects with all oocytes inseminated using ICSI. [10] - Subjects with all oocytes inseminated using ICSI. [11] - Subjects with all oocytes inseminated using ICSI. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Fertilisation rate for each COS cycle | ||||||||||||||||||||
End point description |
Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. Data are presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
Day 1 after oocyte retrieval (19hr ± 2hr)
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| Notes [12] - Subjects with oocytes retrieved. [13] - Subjects with oocytes retrieved. [14] - Subjects with oocytes retrieved. [15] - Subjects with oocytes retrieved. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Number and quality of embryos on Day 3 and blastocysts on Day 5 for each COS cycle | ||||||||||||||||||||||||||||||||||||||||
End point description |
Number and quality of embryos on Day 3 and blastocysts on Day 5 in subjects with oocytes retrieved were presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. Data are presented for the mITT analysis set.
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End point type |
Secondary
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End point timeframe |
Day 3 and Day 5 after oocyte retrieval
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| Notes [16] - Subjects with oocytes retrieved. [17] - Subjects with oocytes retrieved. [18] - Subjects with oocytes retrieved. [19] - Subjects with oocytes retrieved. |
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Circulating concentration of FSH, and luteinising hormone (LH) for each COS cycle | ||||||||||||||||||||||||||||||||||||||||
End point description |
Data are presented for the mITT analysis set.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Stimulation day 6 and end-of-stimulation
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Circulating concentration of estradiol for each COS cycle | ||||||||||||||||||||||||||||||
End point description |
Data are presented for the mITT analysis set.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Stimulation day 6 and end-of-stimulation
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Circulating concentration of progesterone for each COS cycle | ||||||||||||||||||||||||||||||
End point description |
Data are presented for the mITT analysis set.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Stimulation day 6 and end-of-stimulation
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
End point title |
Circulating concentration of Inhibin A, and Inhibin B for each COS cycle | ||||||||||||||||||||||||||||||||||||||||
End point description |
Data are presented for the mITT analysis set.
|
||||||||||||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||||||||||||
End point timeframe |
Stimulation day 6 and end-of-stimulation
|
||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Total gonadotropin dose for each COS cycle | ||||||||||||||||||||
End point description |
The total gonadotropin dose was recorded. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
End-of-stimulation
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Number of stimulation days for each COS cycle | ||||||||||||||||||||
End point description |
The number of stimulation days are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
End-of-stimulation
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Clinical pregnancy rate for each COS cycle | ||||||||||||||||||||
End point description |
Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after blastocyst transfer. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
5-6 weeks after blastocyst transfer
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Vital pregnancy rate for each COS cycle | ||||||||||||||||||||
End point description |
Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
5-6 weeks after blastocyst transfer
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Implantation rate for each COS cycle | ||||||||||||||||||||
End point description |
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
5-6 weeks after blastocyst transfer
|
||||||||||||||||||||
|
|||||||||||||||||||||
| Notes [20] - Subjects with blastocyst transfer. A total of 254 blastocysts were transferred. [21] - Subjects with blastocyst transfer. A total of 271 blastocysts were transferred. [22] - Subjects with blastocyst transfer. A total of 132 blastocysts were transferred. [23] - Subjects with blastocyst transfer. A total of 121 blastocysts were transferred. |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Ongoing pregnancy rate for each COS cycle | ||||||||||||||||||||
End point description |
Ongoing pregnancy rate was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
10-11 weeks after blastocyst transfer
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Ongoing implantation rate for each COS cycle | ||||||||||||||||||||
End point description |
Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
10-11 weeks after blastocyst transfer
|
||||||||||||||||||||
|
|||||||||||||||||||||
| Notes [24] - Subjects with blastocyst transfer. A total of 254 blastocysts were transferred. [25] - Subjects with blastocyst transfer. A total of 271 blastocysts were transferred. [26] - Subjects with blastocyst transfer. A total of 132 blastocysts were transferred. [27] - Subjects with blastocyst transfer. A total of 121 blastocysts were transferred. |
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Proportion of subjects with treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity, after one and after two repeated COS cycles | ||||||||||||||||||||||||||||||
End point description |
The proportion of subjects with treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity, after one and after two repeated COS cycles is presented for the safety analysis set.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Positive βhCG rate for each COS cycle | ||||||||||||||||||||
End point description |
Positive beta unit of human chorionic gonadotropin (βhCG) was confirmed by a blood test 13-15 days after blastocyst transfer. Data are presented for the mITT analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
13-15 days after blastocyst transfer
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
End point title |
Proportion of subjects with markedly abnormal changes in clinical chemistry and haematology parameters for each COS cycle | ||||||||||||||||||||||||||||||
End point description |
Number of subjects with a markedly abnormal value at end-of-stimulation or end-of-trial after a normal baseline value, judged as clinically significant by the investigator (all parameters combined) are presented for the safety analysis set.
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Stimulation day 1, end-of-stimulation and end-of-trial
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
|
|||||||||||||||||||||
End point title |
Frequency of injection site reactions for each COS cycle | ||||||||||||||||||||
End point description |
Subjects self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessment performed is presented for the safety analysis set.
|
||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||
End point timeframe |
End-of-stimulation
|
||||||||||||||||||||
|
|||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Adverse events (AEs) were recorded from signed informed consent to the end-of-cycle visit for COS cycle 2 and again from screening to the end-of-cycle visit for COS cycle 3.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
AEs with onset after start of first administration of IMP and before the end-of-cycle were considered treatment-emergent and are presented for the safety analysis set.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FE 999049 (COS cycle 2)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GONAL-F (COS cycle 2)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 2 were included in this group. Subjects were exposed to the same IMP as in COS cycle 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
FE 999049 (COS cycle 3)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomised to FE 999049 in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
GONAL-F (COS cycle 3)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Subjects randomised to GONAL-F in COS cycle 1 and enrolled and exposed in COS cycle 3 were included in this group. Subjects were exposed to the same IMP as in COS cycles 1 and 2. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| None reported | |||
