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 |
Un nuevo compuesto de FSH recombinante que pretende inducir el desarrollo de múltiples folículos ováricos en mujeres sometidas a estimulación ovárica como parte del tratamiento contra la infertilidad. |
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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 | 14.1 |
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 |
Demostrar la no inferioridad de FE 999049 en comparación con GONAL-F con respecto a la tasa de embarazos en curso y la tasa de implantación en curso en el ciclo fresco en mujeres sometidas a estimulación ovárica controlada |
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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 |
Comparar los beneficios clínicos de FE 999049 en su pauta posológica con los de GONAL-F en lo que respecta a eficacia y seguridad Comparar FE 999049 y GONAL-F en lo que respecta a la respuesta ovárica, incluido el desarrollo folicular y el perfil endocrino, así como en lo que respecta al desarrollo embrionario Comparar FE 999049 y GONAL-F con respecto a la eficacia del tratamiento Comparar FE 999049 y GONAL-F con respecto al perfil de seguridad, incluidos los acontecimientos adversos, los parámetros analíticos rutinarios de seguridad y la tolerabilidad local Evaluar la inmunogenicidad de FE 999049 después de un ciclo de tratamiento Comparar FE 999049 y GONAL-F con respecto a la relación coste-beneficio |
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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. |
En este estudio se incluirán mujeres sometidas al primer ciclo de FIV/ICSI y con una edad comprendida entre 18 y 40 años. Se les debe haber diagnosticado infertilidad tubárica, infertilidad no fundamentada o endometriosis de fase I/II o sus parejas deben tener un diagnóstico de infertilidad masculina, y se las debe considerar elegibles para tratamiento de FIV o ICSI. El índice de masa corporal (IMC) permitido es de 17,5 - 32,0 kg/m2, lo que incluye a pacientes con un peso inferior al normal, con peso normal, con sobrepeso y con obesidad. |
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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. |
En este estudio se excluirán pacientes con endometriosis de fase III/IV, antecedentes de abortos espontáneos recurrentes o en las que la estimulación ovárica controlada con gonadotropinas esté contraindicada. |
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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) |
1. Tasa de embarazos en curso (al menos un feto viable intrauterino 10 - 11 semanas después de la transferencia) 2. Tasa de implantación en curso (número de fetos viables intrauterinos 10 - 11 semanas después de la transferencia, dividido entre el número de blastocistos transferidos) |
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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 |
1. 10-11 semanas tras la transferencia 1. 10-11 semanas tras la transferencia |
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E.5.2 | Secondary end point(s) |
1. Positive ?hCG (positive serum ?hCG 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 |
1. Tasa de ?hCG positiva (prueba de ?hCG en suero positiva 13 - 15 días después de la transferencia) 2. Tasa de embarazos clínicos (de al menos un saco gestacional 5 - 6 semanas después de la transferencia) 3. Tasa de embarazos vitales (al menos un saco gestacional intrauterino con latido cardíaco fetal 5 - 6 semanas después de la transferencia) 4. Tasa de implantación (número de sacos gestacionales 5 - 6 semanas después de la transferencia, dividido entre el número de blastocistos transferidos) 5. Porcentaje de sujetos con respuestas ováricas extremas, definidas como < 4, ? 15 o ? 20 ovocitos recuperados 6. Porcentaje de sujetos con SHO prematuro (incluido SHO moderado/grave) y/o intervenciones preventivas para el SHO prematuro 7. Porcentaje de pacientes con cancelación del ciclo debido a una respuesta ovárica deficiente o una respuesta ovárica excesiva 8. Número y tamaño de los folículos el día 6 de estimulación y al final de la estimulación 9. Porcentaje de ovocitos en metafase II (aplicable solamente a los inseminados utilizando ICSI), tasa de fecundación, así como el número y la calidad de los embriones el día 3 y de los blastocistos el día 5 después de la recuperación de ovocitos 10. Concentraciones circulatorias de FSH, LH, estradiol, progesterona, inhibina A e inhibina B el día 6 de estimulación y al final de la estimulación 11. Dosis total de gonadotropina y número de días de estimulación 12. Frecuencia e intensidad de los acontecimientos adversos 13. Cambios en las concentraciones circulantes de los parámetros de bioquímica clínica y hematológicos y porcentaje de pacientes con cambios anómalos acusados 14. Frecuencia e intensidad de las reacciones en el lugar de inyección (enrojecimiento, dolor, prurito, tumefacción y hematoma) evaluadas por la paciente durante el periodo de estimulación |
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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 |
1. 13-15 días tras la transferencia 2. 5-6 semanas tras la transferencia 3. 5-6 semanas tras la transferencia 4. 5-6 semanas tras la transferencia 5. Visita de recuperación de ovocitos 6. 9 días tras la activación 7. Fin de estimulación 8. Estimulación día 6 y fin de estimulación 9. Antes de la inseminación, cultivo día 1, cultivo día 3 y cultivo día 5 10. Estimulación día 6 y fin de estimulación 11. Fin de estimulación 12. Desde la firma de consentimiento informado hasta la visita de fin de ensayo 13. Estimulación día 1, fin de la estimulación y fin de ensayo 14. Fin de estimulación |
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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 |
Evaluador ciego |
Assessor blinded |
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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 | 9 |
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 |
Brazil |
Canada |
European Union |
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 |
Última visita del último paciente en la fase de seguimiento tras su finalización en el ensayo clínico |
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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 | 3 |
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 |