E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Women diagnosed with tubal infertility or unexplained infertility or endometriosis stage I/II or having partners diagnosed with male factor infertility, eligible for IVF and/or ICSI. |
Mujeres diagnosticadas con infertilidad tubárica, infertilidad idiopática, endometriosis en estadios I/II o con parejas con diagnóstico de infertilidad por factor masculino, consideradas aptas para FIV o IICE. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10021940 |
E.1.2 | Term | Infertility, female, of unspecified origin |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016403 |
E.1.2 | Term | Female infertility of tubal origin |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025511 |
E.1.2 | Term | Male infertility, unspecified |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014787 |
E.1.2 | Term | Endometriosis of uterus |
E.1.2 | System Organ Class | 100000004872 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10014784 |
E.1.2 | Term | Endometriosis of ovary |
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 |
To investigate the effects of FE 999302 on parameters influencing pregnancy rates in women undergoing COS with follitropin delta in a long GnRH agonist protocol |
Investigar los efectos de FE 999302 en los parámetros que influyen en las tasas de embarazo en mujeres sometidas a EOC con folitropina delta en un protocolo largo con un agonista de la GnRH |
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E.2.2 | Secondary objectives of the trial |
- To investigate the safety of FE 999302 in women undergoing COS with follitropin delta in a long GnRH agonist protocol - To investigate the potential immunogenicity of FE 999302 in subjects undergoing COS with follitropin delta in a long GnRH agonist protocol - To estimate the impact of body weight on FE 999302 exposure in subjects undergoing COS with follitropin delta in a long GnRH agonist protocol |
-Investigar la seguridad de FE 999302 en mujeres sometidas a EOC con folitropina delta en un protocolo largo con un agonista de la GnRH -Investigar la inmunogenicidad potencial de FE 999302 en pacientes sometidas a EOC con folitropina delta en un protocolo largo con un agonista de la GnRH -Calcular la influencia del peso corporal sobre la exposición a FE 999302 en pacientes sometidas a EOC con folitropina delta en un protocolo largo con un agonista de la GnRH |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent documents signed prior to screening evaluations. 2. In good physical and mental health as judged by the investigator. 3. Anti-Müllerian hormone (AMH) levels at screening of 5.0-35.0 pmol/L (as measured by Elecsys® AMH Plus Immunoassay [Roche Diagnostics] at central laboratory). 4. Pre-menopausal women between the ages of 30 and 42 years. The subjects must be at least 30 years (including the 30th birthday) and no more than 42 years (up to the day before the 43rd birthday) when they sign the informed consent. 5. Infertile women diagnosed with tubal infertility, unexplained infertility, endometriosis stage I/II or with partners diagnosed with male factor infertility, eligible for in vitro fertilisation (IVF) and/or intracytoplasmic sperm injection (ICSI) using fresh or frozen ejaculated sperm from male partner or sperm donor. 6. Infertility for at least 1 year before screening for subjects <35 years or for at least 6 months for subjects ≥35 years (not applicable in case of tubal or severe male factor infertility).
For further inclusion criteria refer to protocol v 2.0 dated 15Dec2017 |
1. Firma de los formularios de consentimiento informado antes de las evaluaciones de la selección. 2. Encontrarse en buen estado físico y mental según el criterio del investigador. 3. Niveles de hormona antimülleriana (AMH) en la selección de 5,0-35,0 pmol/l (medida según el inmunoanálisis Elecsys® AMH Plus [Roche Diagnostics] en el laboratorio central). 4. Mujeres premenopáusicas entre 30 y 42 años de edad. Las pacientes deben tener al menos 30 años (incluido el 30o cumpleaños) y no más de 42 años (hasta la víspera del 43o cumpleaños) cuando firmen el consentimiento informado. 5. Mujeres infértiles con diagnóstico de infertilidad tubárica, infertilidad idiopática, endometriosis de estadios I/II o cuyas parejas tengan un diagnóstico de infertilidad por factor masculino, que sean aptas para la fertilización in vitro (FIV) o la inyección intracitoplásmica de espermatozoides (IICE) utilizando semen fresco o congelado eyaculado de su pareja masculina o de un donante de semen. 6. Infertilidad durante al menos 1 año antes de la selección en el caso de las pacientes <35 años o durante al menos 6 meses en el caso de las pacientes ≥35 años (no aplicable en caso de infertilidad tubárica o infertilidad grave por factor masculino).
Para el resto de criterios de inclusión, ver el protocolo versión 2.0 de 15 de diciembre de 2017. |
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E.4 | Principal exclusion criteria |
1. Known polycystic ovary syndrome (PCOS) associated with anovulation or known endometriosis stage III-IV (defined by the revised American Society for Reproductive Medicine [ASRM] classification, 1996). 4. One or more follicles ≥10 mm (including cysts) observed on the transvaginal ultrasound after down-regulation prior to randomisation on stimulation day 1 (puncture of cysts is allowed prior to randomisation). 20. Pregnancy (negative pregnancy tests must be documented at screening and prior to start of down-regulation) or contraindication to pregnancy.
For further exclusion criteria refer to protocol v 2.0 dated 15Dec2017 |
1.Síndrome del ovario poliquístico (SOP) conocido asociado a anovulación o endometriosis conocida en estadio III-IV (definida según la clasificación revisada de la American Society for Reproductive Medicine [ASRM] de 1996). 2.Respuesta insuficiente en un ciclo anterior de estimulación ovárica controlada para FIV/IICE, definida como desarrollo de <4 ovocitos con un diámetro ≥12 mm. 3.Respuesta ovárica excesiva en un ciclo anterior de estimulación ovárica controlada para FIV/IICE, definida como desarrollo de ≥25 ovocitos con un diámetro ≥12 mm. 4.Presencia de uno o más folículos ≥10 mm (incluidos quistes) en la ecografía transvaginal después de la regulación a la baja antes de la aleatorización el día 1 de la estimulación (se permite puncionar los quistes antes de la aleatorización). 20.Embarazo (deben documentarse pruebas de embarazo negativas en la selección y antes de empezar la regulación a la baja) o contraindicación de embarazo.
Para el resto de criterios de exclusión, ver el protocolo versión 2.0 de 15 de diciembre de 2017. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Number of good-quality blastocysts on day 5 after oocyte retrieval (grade 3BB or higher) |
Número de blastocistos de buena calidad el día 5 posterior a la recuperación de los ovocitos (grado 3BB o superior) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
day 5 after oocyte retrieval |
día 5 posterior a la recuperación de los ovocitos |
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E.5.2 | Secondary end point(s) |
- Number and quality of embryos on day 3 after oocyte retrieval - Number and quality of blastocysts on day 5 after oocyte retrieval - Changes in serum hormone levels from stimulation day 1 to stimulation day 6, stimulation day 8, end-of-stimulation (progesterone, 17-OH-progesterone, androstenedione, testosterone, estradiol, inhibin A, inhibin B, FSH, and LH), and oocyte retrieval (progesterone, 17-OH-progesterone, androstenedione, testosterone, estradiol) - Positive βhCG (positive serum βhCG test 13-15 days after transfer) -Clinical pregnancy (at least one gestational sac 5-6 weeks after transfer) - Vital pregnancy (at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after transfer) - Ongoing pregnancy (at least one intrauterine viable fetus 10-11 weeks after transfer) - Number of oocytes retrieved - Number of metaphase II oocytes - Number of fertilised (2PN) oocytes - Incidence of ovarian hyperstimulation syndrome (early or late, any grade) - Incidence and intensity of adverse events |
-Número y calidad de los embriones el día 3 posterior a la recuperación de los ovocitos -Número y calidad de los blastocistos el día 5 posterior a la recuperación de los ovocitos -Cambios en los niveles hormonales en suero desde el día 1 de la estimulación hasta el día 6 de la estimulación, el día 8 de la estimulación, el final de la estimulación (progesterona, 17-OH-progesterona, androstenediona, testosterona, estradiol, inhibina A, inhibina B, FSH y LH) y la recuperación de los ovocitos (progesterona, 17-OH-progesterona, androstenediona, testosterona y estradiol) -βhCG positiva (prueba de βhCG en suero positiva a los 13-15 días de la transferencia) -Embarazo clínico (al menos un saco gestacional a las 5-6 semanas de la transferencia) -Embarazo vital (al menos un saco gestacional intrauterino con latido cardíaco fetal a las 5-6 semanas de la transferencia) -Embarazo en curso (al menos un feto intrauterino viable a las 10-11 semanas de la transferencia) -Número de ovocitos recuperados -Número de ovocitos en metafase II -Número de ovocitos fertilizados (2PN) -Incidencia del síndrome de hiperestimulación ovárica (temprano o tardío, de cualquier grado) -Incidencia e intensidad de los acontecimientos adversos |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Timepoint is included in the relevant endpoint |
El momento temporal está indicado en cada uno de los criterios de valoración |
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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 | No |
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 | Yes |
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) | 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 | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| 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 | 20 |
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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LVLS |
Última visita del último paciente |
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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 | |
E.8.9.1 | In the Member State concerned months | 23 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial months | 23 |
E.8.9.2 | In all countries concerned by the trial days | 0 |