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 | 14.0 |
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 investigate the dose-response relationship of FE 999049 with respect to ovarian response in patients undergoing controlled ovarian stimulation |
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E.2.2 | Secondary objectives of the trial |
To evaluate the dose-response relationship of FE 999049 with respect to endocrine profile, oocyte fertilisation, number and quality of embryos and treatment efficiency
To evaluate the efficacy of FE 999049 with respect to achieving pregnancy
To assess the population pharmacokinetics of FE 999049
To evaluate the safety profile of FE 999049
To evaluate the local tolerability of FE 999049 following subcutaneous administration
To evaluate the immunogenicity of FE 999049
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Women diagnosed with tubal infertility, unexplained infertility, infertility related to endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for IVF and/or ICSI treatment will be included in this trial. Subjects will be 18-37 years of age, with a body mass index (BMI) of 18.5-32.0 kg/m2 and have serum AMH levels within 5.0-44.9 pmol/L at the screening visit based on the central laboratory analysis. |
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E.4 | Principal exclusion criteria |
Women with polycystic ovary syndrome (PCOS) associated with anovulation, endometriosis stage III/IV, history of recurrent miscarriage or with contraindications to controlled ovarian stimulation with gonadotropins will be excluded from participation in this trial. Women with three or more controlled ovarian stimulation cycles will also be excluded. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of oocytes retrieved |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Oocyte retrieval is performed when the following criteria is met:
• ≥3 follicles with a diameter ≥17 mm
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E.5.2 | Secondary end point(s) |
1. Number and size of follicles during stimulation
2. Circulating levels of FSH during stimulation and FSH population pharmacokinetic parameters
3. Circulating levels of LH, inhibin A, inhibin B, estradiol, progesterone, total testosterone and sex hormone binding globulin (SHBG) (free androgen index (FAI) to be calculated) during stimulation
4. Total FE 999049 or GONAL-F dose administered and number of stimulation days
5. Number of fertilised oocytes and fertilisation rate as well as number and quality of embryos on day 3 and blastocysts on day 5
6. Positive βhCG rate (positive serum βhCG test 13-15 days after embryo transfer)
7. Clinical pregnancy (with fetal heart beat) rate (transvaginal ultrasound showing at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after embryo transfer)
8. Frequency and intensity of adverse events
9. Changes in circulating levels of clinical chemistry and haematology parameters and proportion of subjects with markedly abnormal changes
10. Frequency and intensity of injection site reactions (redness, pain, itching, swelling and bruising) assessed by the subject three times daily during the stimulation period
11. Proportion of subjects with treatment-induced anti-FSH antibodies
12. Proportion of subjects with treatment-induced anti-FSH antibodies with neutralising capacity
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Evaluated at each visit during stimulation
2. Day 4, day 6 and each subsequent stimulation visits
3. Day 4, day 6 and each subsequent stimulation visits
4. End of stimulation day
5. Day 0 to day 5 after oocyte retrieval
6. βhCG test 13-15 days after embryo transfer
7. 5-6 weeks after embryo transfer
8. From signing informed consent until end of trial visit
9. End of stimulation and End of trial
10. Evaluated 3 times daily during the stimulation period
11. 8-10 days after last IMP dose and 21-28 days after last IMP dose
12. Evaluation performed after last sample, first sample taken predosing, second 8-10 days after last IMP dose, third 21-28 days after last IMP dose |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 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 | 6 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | Yes |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |