| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Stimulation of multifollicular development in women undergoing
superovulation for assisted reproductive technologies (ART) such as in vitro fertilisation (IVF), gamete intra-fallopian transfer and zygote intrafallopian transfer. |
|
| E.1.1.1 | Medical condition in easily understood language |
| To make the woman's body produce a number of eggs at the same, which can be removed by doctors for infertility treatments. |
|
| 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 | PT |
| E.1.2 | Classification code | 10021928 |
| E.1.2 | Term | Infertility female |
| E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
|
| 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 |
| To demonstrate equivalence between the numbers of oocytes retrieved after treatment with Watson rhFSH or GONAL-f in ovulatory subjects participating in an ART program. |
|
| E.2.2 | Secondary objectives of the trial |
• To evaluate pregnancy rate after treatment with Watson rhFSH and GONAL-f.
• To evaluate the dose requirements and duration of Watson rhFSH and GONAL-f
treatment.
• To evaluate the pharmacodynamic properties of Watson rhFSH and GONAL-f.
• To evaluate the number of good quality oocytes and embryos after treatment with
Watson rhFSH and GONAL-f.
• To evaluate immunogenicity, in terms of anti-FSH antibodies, after treatment with
Watson rhFSH and GONAL-f.
• To evaluate the general safety of Watson rhFSH and GONAL-f.
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
IN01. Is in good health and 18 to 35 years of age (inclusive) with child-bearing potential at the time of screening;
IN02. Has a body mass index (BMI) of 18 – 32 (inclusive);
IN03. Has adequate ovarian reserve as measured by: a) the serum FSH level during the early
follicular phase (menstrual cycle day 2, 3 or 4) is less than 2x the upper range of normal for the study population at Screening and b) the serum anti-Mullerian hormone (AMH) level is between 1.0 to 4.5 ng/mL (i.e., 1.0 ng/mL < AMH < 4.5 ng/mL) at Screening;
IN04. Has a current diagnosis of infertility with one of the following categories: tubal factor, ovulation disorder, mild endometriosis (American Society for Reproductive
Medicine [ASRM] stage 1-2), male factor, other causes, unexplained cause, multiple factors (female only), and multiple factors (male and female);
IN05. Has both ovaries (by ultrasonography at Screening) and normal uterine cavity;
IN06. Has a male partner with semen analysis that is at least adequate for ICSI within 6 months before the first test or reference article injection (Surgically-removed or
donor sperm, if adequate for ICSI, is allowed.);
IN07. Has LH, prolactin (PRL), thyroid stimulating hormone (TSH) results within the
reference range for the clinical laboratory or considered not clinically significant by
the Investigator at Screening;
IN08. Has current general health status that is congruent with the site’s conventional
requirements for ART eligibility;
IN09. Is willing and able to comply with the requirements of the protocol;
IN10. Is willing and able to provide written informed consent and authorisation to disclose
after being fully informed of the risks of participating in the study. |
|
| E.4 | Principal exclusion criteria |
EX01. Has participated in another study protocol or in a clinical trial with experimental medication within 30 days of Screening;
EX02. Has participated in previous ART cycle before this study;
EX03. Has taken clomiphene, tamoxifen, injectable GnRH agonists or antagonists, estrogen, androgens, anti-androgens, synthetic progestins, or aromatase inhibitors within 30 days of Screening;
EX11. Has 12 or more follicles in either ovary, size 2 - 9 mm in diameter (calculated as the mean of the longitudinal and anteroposterior diameters) and/or an ovarian volume > 10 mL in either ovary (calculated using the formula 0.5 x length x width x thickness), as determined by transvaginal ultrasound examination at Screening Visit 3
or on Treatment Day 1 before the first test or reference article injection;
EX12. Has symptoms or signs of pelvic or vaginal infection or abnormal gynecological bleeding;
EX13. Has current diagnosis of or signs and symptoms that indicate adrenal dysfunction;
EX14. Has a history of recurrent spontaneous abortion (3 or more);
EX15. Has a history of extrauterine pregnancy in the past 6 months before Screening;
EX16. Has a history of allergy or hypersensitivity to any protein based drugs, including FSH and hCG products and GnRH antagonists, or any excipient in the formulation of the test or reference articles;
EX17. Is a smoker with an average > 5 cigarettes (or equivalent tobacco use of other types) a day;
EX18. Is unable or unwilling to tolerate injections;
EX19. Is judged by the Investigator to be unsuitable for enrollment for any other reason.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Number of oocytes retrieved in the first ART cycle |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Evaluated at the end of the first ART cycle. The overall treatment duration in any ART cycle will not exceed 19 days with average expected to be around 10 days. |
|
| E.5.2 | Secondary end point(s) |
1. Ongoing pregnancy rate, defined as percentage of subjects with presence of at least one fetus with heart activity, at 10 weeks after embryo transfer;
2. Mean total dose of Actavis rhFSH or GONAL-f required during the ART
cycle;
3. Mean number of days of Actavis rhFSH or GONAL-f stimulation during
the ART cycle;
4. Percentage of subjects who require an increase or decrease of the dose of Actavis rhFSH or GONAL-f during treatment;
5. Mean number of follicles/cysts with sizes ≥ 11 mm, ≥ 15 mm, or ≥ 17 mm on Treatment Day 6 (before FSH dose adjustment) and the day of hCG administration;
6. Serum concentrations of inhibin-B, E2, LH, FSH, and progesterone on
Treatment Day 1 (before Actavis rhFSH or GONAL-f injection) and the day of hCG administration;
7. Mean number of fertilised oocytes at 24 hours after the initiation of
the IVF for subjects who are not choosing ICSI procedure;
8. Mean number of metaphase II oocytes after oocyte retrieval for
subjects with ICSI procedure (metaphase II oocytes are defined as
having extruded the first polar body and are in the resting phase of
meiosis II);
9. Mean number of Grade 1 and Grade 2 embryos on Day 3 of embryo
culture. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Ongoing pregnancy rate (1) will be evaluated at 10 weeks after embryo
transfer. Other secondary endpoints (2, 3, 4, 8) are evaluated at the end
of the first ART cycle (as for the primary endpoint). Endpoint (5) on
Treatment Day 6 (before FSH dose adjustment) and the day of hCG
administration, and (6) on Treatment Day 1 (before FSH injection) and
the day of hCG administration. Mean number of fertilised oocytes (7)
assessed at 24 hours after the initiation of the IVF for subjects who are
not choosing ICSI procedure. Mean number of Grade 1 and Grade 2
embryos (9) assessed on Day 3 of embryo culture. |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
|
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| 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
|
|
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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