E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Poor Ovarian Response i.e. a failure to respond adequately to standard ART (assisted reproductive technologies) protocols and to recruit adequate follicles |
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E.1.1.1 | Medical condition in easily understood language |
Poor Ovarian Response describes a less than expected response to standard treatments for infertility due to reduced production of eggs in the ovaries |
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E.1.1.2 | Therapeutic area | Body processes [G] - Reproductive physiologi cal processes [G08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033140 |
E.1.2 | Term | Ovarian disorder NOS |
E.1.2 | System Organ Class | 100000004872 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to demonstrate superiority of Pergoveris® versus GONAL-f® in poor ovarian response (POR) patients. |
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E.2.2 | Secondary objectives of the trial |
Key secondary objectives will include assessment of other clinical variables that reflect the efficacy of ovarian stimulation and safety assessment of combination treatment with recombinant human follicle-stimulating hormone (r-hFSH) and recombinant human luteinizing r-hLH (Pergoveris®) as compared to r-hFSH (GONAL-f®)-only treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The current trial will enroll poor ovarian responders as aligned with the 2011 Consensus Meeting of the ESHRE
1. Subject must be a poor responder
at least 2 of the following 3 features must be present:
● ESHRE criteria = Advanced maternal age (≥ 40 years) or any risk factor for POR - INCLUSION for this study: Yes (< 41 years), no for any risk factor
● ESHRE Criteria = A previous POR (≤ 3 oocytes with a conventional stimulation protocol)
INCLUSION for this study: Yes
● ESHRE Criteria = An abnormal ovarian reserve test (ORT) (ie, anti-mullerian hormone [AMH] < 0.5 - 1.1 ng mL)
INCLUSION for this study: Yes for AMH only (≥ lower limit of assay detection – 1.3 ng/mL, inclusive)
Additional inclusion criteria are:
2.Female subjects, 18 to < 41 years of age (according to date of birth at time of informed consent) who are eligible for ovarian stimulation and ART treatment, including ICSI
3.Absence of anatomical abnormalities of the reproductive tract that would interfere with implantation or pregnancy
4.Absence of any medical condition in which pregnancy is contraindicated
5.Body mass index 18 to 30 kg/m2, inclusive
6.Motile, ejaculatory sperm must be available (donated and/or cryopreserved sperm is allowed). Intracytoplasmic sperm injection will be allowed during this trial.
7.Minimum of 1 month without treatment with either clomiphene citrate or gonadotrophins prior to screening
8.Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment
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E.4 | Principal exclusion criteria |
1.Primary ovarian failure
2.Preimplantation genetic screening or diagnosis
3.Two episodes of POR after maximal stimulation
4.History or presence of tumors of the hypothalamus or pituitary gland
5.History or presence of ovarian enlargement or cyst of unknown etiology, or presence of an ovarian cyst > 25 mm on the day of randomization
6.Presence of endometriosis Grade III – IV, confirmed or suspected
7.Presence of uni- or bilateral hydrosalpinx
8.Abnormal gynecological bleeding of undetermined origin
9.Malformations of sexual organs incompatible with pregnancy
10.Contraindication to being pregnant and/or carrying a pregnancy to term
11.Currently pregnant
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E.5 End points |
E.5.1 | Primary end point(s) |
Total number of retrieved oocytes. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On/before day 113 (Visit 12) |
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E.5.2 | Secondary end point(s) |
• Ongoing pregnancy rate (assessed on/before day 185 -Visit 16).
• Live birth rate (assessed on/before day 365 - Visit 17).
• Embryo implantation rate (determined on/before day 154 - Visit 15).
• Clinical pregnancy rate (determined on/before day 154 - Visit 15).
• Biochemical pregnancy rate (determined on/before day 132 - Visit 14).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Visits 14 to 17 as described above |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Yes |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 79 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Czech Republic |
Denmark |
Estonia |
Finland |
France |
Germany |
Hungary |
Italy |
Latvia |
Netherlands |
Poland |
Russian Federation |
Spain |
Sweden |
Turkey |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 12 |