E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
A new recombinant FSH (follicle-stimulating hormone) compound intended to induce development of multiple egg sacs in women undergoing ovarian stimulation as part of infertility treatment |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021926 |
E.1.2 | Term | Infertility |
E.1.2 | System Organ Class | 10038604 - Reproductive system and breast disorders |
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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 |
To demonstrate non-inferiority of FE 999049 compared with GONAL-F with respect to ongoing pregnancy rate and ongoing implantation rate in the fresh cycle in women undergoing controlled ovarian stimulation |
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E.2.2 | Secondary objectives of the trial |
To compare the clinical benefits of FE 999049 in its dosing regimen to those of GONAL-F with respect to efficacy and safety
To compare FE 999049 with GONAL-F with respect to ovarian response including follicular development and endocrine profile, as well as with respect to embryo development
To compare FE 999049 with GONAL-F with respect to treatment efficiency
To compare FE 999049 with GONAL-F with respect to safety profile, including adverse events, routine safety laboratory parameters and local tolerability
To evaluate the immunogenicity of FE 999049 after one treatment cycle
To compare FE 999049 with GONAL-F with respect to cost-effectiveness |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
This trial will include women undergoing their first IVF/ICSI cycle and aged 18-40 years. They have been diagnosed with tubal infertility, endometriosis stage I/II or have partners diagnosed with male factor infertility, and are considered eligible for IVF or ICSI. The allowed body mass index (BMI) is 17.5 – 32.0 kg/m2, thus including underweight, normal weight, overweight and obese patients. |
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E.4 | Principal exclusion criteria |
Subjects with endometriosis stage III/IV, known history of recurrent miscarriage or with contraindications to controlled ovarian stimulation with gonadotropins will be excluded from participation in this trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Ongoing pregnancy rate (at least one intrauterine viable fetus 10-11 weeks after transfer)
2. Ongoing implantation rate (number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocytes transferred)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. 10-11 weeks after transfer
2. 10-11 weeks after transfer
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E.5.2 | Secondary end point(s) |
1. Positive βhCG (positive serum βhCG test 13-15 days after transfer)
2. Clinical pregnancy rate (at least one gestational sac 5-6 weeks after transfer)
3. Vital pregnancy rate (at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer)
4. Implantation rate (number of gestational sacs 5-6 weeks after transfer divided by number of blastocytes transferred)
5. Proportion of subjects with extreme ovarian responses, defined as < 4, ≥ 15 or ≥ 20 oocytes retrieved
6. Proportion of subjects with early OHSS (including OHSS of moderate/severe grade) and/or preventive interventions for early OHSS
7. Proportion of subjects with cycle cancellation due to poor ovarian response or excessive ovarian response
8. Number and size of follicles on stimulation day 6 and end-of-stimulation
9. Percentage of metaphase II oocytes (only applicable for those inseminated using ICSI), fertilization rate as well as number and quality of embryos on day 3 and blastocytes on day 5 after oocyte retrieval
10. Circulating concentrations of FSH, LH, estradiol, progesterone, inhibin A and inhibin B on stimulation day 6 and end-of-stimulation
11. Total gonadotropin dose and number of stimulation days
12. Frequency and intensity of adverse events
13. Changes in circulating levels of clinical chemistry and haematology parameters and proportion of subjects with markedly abnormal changes
14. Frequency and intensity of injection site reactions (redness, pain, itching, swelling and bruising) assessed by subject during the stimulation period |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 13-15 days after transfer
2. 5-6 weeks after transfer
3. 5-6 weeks after transfer
4. 5-6 weeks after transfer
5. Oocyte retrieval visit
6. 9 days after triggering
7. End-of-stimulation
8. Stimulation day 6 and end-of-stimimulation
9. Prior to insemination, culture day 1, culture day 3 and culture day 5
10. Stimulation day 6 and end-of-stimulation
11. End-of-stimulation
12. From signing Informed consent until end-of-trial visit
13. Stimulation day 1, end-of-stimulation and end-of-trial
14. End-of-stimulation |
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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 | No |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
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 |
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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 | 20 |
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 |
Canada |
European Union |
Brazil |
Mexico |
Russian Federation |
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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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LVLS in the post-trial follow-up phase of the study |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 3 |