E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Infertility in women with poor ovarian response to stimulation for IVF/ICSI |
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E.1.1.1 | Medical condition in easily understood language |
Poor ovarian responders are women undergoing infertility treatment who failed to produce adequate number of oocytes after ovarian stimulation treatment in previous treatment cycles for IVF/ICSI |
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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 | 20.0 |
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 |
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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 |
Clinical pregnancy rate defined as the presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 7 weeks of gestation |
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E.2.2 | Secondary objectives of the trial |
a.Ongoing pregnancy rate defined as the presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation b.Biochemical pregnancy defined as positive pregnancy test 2 weeks after embryo transfer c.Number of oocytes retrieved after oocyte retrieval before ICSI d.Cycle cancellation due to poor response e.Number of cycles reaching the stage of embryo transfer f.Number and quality of embryos g.Number of cycles with frozen supernumerary embryos h.Cycle cancellation due to adverse effects of medication |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. Evaluation of endocrine profile during androgen supplementation Blood samples will be collected from each of the participating centres and will be kept frozen for analysis in the central lab in UZ Brussel. Endocrine profile analysis will be performed (Total testosterone (TT), DHEAS, Sex hormone-binding globulin (SHBG), IGF-1etc.) and will be compared between testosterone and placebo groups 2. Differences in ovarian reserve markers Comparisons between AMH levels and AFC will be evaluated during testosterone and placebo supplementation and blood samples will be collected from each of the participating centres and will be kept frozen for analysis in the central lab in UZ Brussel. Analysis of AMH and AFC and will be compared between testosterone and placebo groups in order to evaluate the effect of testosterone ovarian reserve markers 3. Follicular fluid analysis The participating centre and centres with expertise of collecting follicular fluid will collect follicular fluid samples from oocyte retrieval and separate analysis will be performed in order to evaluate concentration or testosterone, IGF1, FSH receptors etc. in the follicular fluid and correlate values with androgen levels in the blood. 4 Use of Fertiqol questionnaire to evaluate quality of life for patients prior to initiating treatment and on the day of following termination of testosterone treatment. We will use the validated Fertiqol questionnaire (psych.af.ac.uk/fertiqol) to evaluate quality of life at the screening visit and on the day after the last testosterone dose in order to evaluate the effect of androgen supplementation on quality of life of individuals enrolled in the study ( find questionnaires attached) 5. Use of FSFI and FSDS-R questionnaires to evaluate sexual function and sexual distress We will use the validated FSFI and FSDS-R questionnaires to evaluate sexual function and sexual distress at the screening visit and on the day of after the last testosterone dose in order to evaluate the effect of androgen supplementation on sexual life of individuals enrolled in the study 6. Use of Ferriman-Gallwey Hirsutism scoring system. Gallwey Hirsutism Score at the screening visit and on the day of after the last testosterone dose in order to evaluate the effect of androgen supplementation on hirsutism of individuals enrolled in the study.
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E.3 | Principal inclusion criteria |
Patients participating in the TTRANSPORT study will be women who are considered poor ovarian responders according to the “Bologna criteria” (Ferraretti et al., 2011). Subjects must fulfil the following criteria to be included in the study: 1. All subjects must sign the Informed consent documents prior to screening evaluations. 2.Age: between 18-43 years old. 3.One of the features below: Infertile female <40 years old with i.≤ 3 oocytes in a previous cycle and AFC <7 OR ii.ovarian surgery/chemotherapy and AFC<7 OR iii.≤ 3 oocytes in at least 2 previous cycles with ≥300IU gonadotropins Infertile female ≥40 years old with i. ≤ 3 oocytes in a previous cycle OR ii. AFC <7.
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E.4 | Principal exclusion criteria |
1.Perimenopausal women with amenorrhea not having a regular cycle 2.Basal FSH >20 IU/l 3.Uterine malformations 4.Recent history of any current untreated endocrine abnormality 5.Unilateral or bilateral hydrosalpinx (visible on USS, unless clipped) 6.Contraindications for the use of gonadotropins 7.Recent history of severe disease requiring regular treatment 8.Use of androgens during the last 3 months 9.Patients with SHBG values <20nmol/L or >160nmol/L 10.Azoospermia (sperm derived through FNA or TESE) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the clinical pregnancy rates, defined as defined as the presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 7 weeks of gestation. The primary efficacy endpoint is related to the primary trial objective. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are: 1.Cycle cancellation due to poor ovarian response 2.Cycles with embryo transfer 3.Ongoing pregnancy rate (the presence of intrauterine gestational sac with an embryonic pole demonstrating cardiac activity at 9-10 weeks of gestation) 4.Biochemical pregnancy (defined as positive pregnancy test 2 weeks after embryo transfer) 5.Number of cumulus oocyte complexes (COCs) retrieved 6.Number of MII oocytes retrieved
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 9-10 weeks of gestation 2. 2 weeks after embryo transfer 3. 10 -20 days from initiation of ovarian stimulation 4. 10-20 days from initiation of ovarian stimulation 5. 10 days after initiation of daily injections of HP-hMG 6. 10-20 days from initiation of ovarian 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 | 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 | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| Yes |
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 | 13 |
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 |
Denmark |
Spain |
Switzerland |
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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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last visit of the last subject enter LVLS |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |