Phase 3 Study to Evaluate the Efficacy and Safety of Pergoveris® in Assisted Reproductive Technology (ESPART)

Study Overview
=================
Brief Summary
-----------------
This is a Phase 3, randomized, controlled, single-blind, multicenter, parallel-arm trial to assess the safety and efficacy of Pergoveris® (recombinant human follicle stimulating hormone [r-hFSH]/recombinant human luteinising hormone [r-hLH]) and GONAL-f® for multifollicular development as part of an assisted reproductive technology (ART) treatment cycle in poor ovarian responders, as aligned with the 2011 Consensus Meeting of the European Society of Human Reproduction and Embryology (ESHRE) criteria.

Official Title
-----------------
A Phase III, Randomized, Controlled, Single-blind, Multicentre, Parallel Arm Trial to Assess the Efficacy and Safety of Pergoveris® (Follitropin Alfa and Lutropin Alfa) and GONAL-f® (Follitropin Alfa) for Multifollicular Development as Part of an Assisted Reproductive Technology Treatment Cycle in Poor Ovarian Responders, as Defined by the European Society of Human Reproduction and Embryology Criteria

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Drug: Pergoveris®
* Drug: GONAL-f®
* Drug: Recombinant human chorionic gonadotrophin (r-hCG)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Poor ovarian responders according to specific criteria that are aligned with poor ovarian response (POR) criteria defined by the 2011 Consensus Meeting of the European Society of Human Reproduction and Embryology (ESHRE) as mentioned in the protocol Female subjects, less than (<) 41 years of age (according to date of birth at time of informed consent) who are eligible for ovarian stimulation and ART treatment, including intracytoplasmic sperm injection (ICSI) Absence of anatomical abnormalities of the reproductive tract that would interfere with implantation or pregnancy Absence of any medical condition in which pregnancy is contraindicated Body mass index 18 to 30 kilogram per square meter (kg/m^2), inclusive Motile, ejaculatory sperm must be available (donated and/or cryopreserved sperm is allowed). Intracytoplasmic sperm injection will be allowed during this trial Minimum of 1 month without treatment with either clomiphene citrate or gonadotrophins prior to screening Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment Exclusion Criteria: Two episodes of POR after maximal stimulation History or presence of tumors of the hypothalamus or pituitary gland History or presence of ovarian enlargement or cyst of unknown etiology, or presence of an ovarian cyst greater than 25 mm on the day of randomization Presence of endometriosis Grade III - IV, confirmed or suspected Presence of uni- or bilateral hydrosalpinx Abnormal gynecological bleeding of undetermined origin Contraindication to being pregnant and/or carrying a pregnancy to term History or presence of ovarian, uterine or mammary cancer Use of testicular or epididymal sperm Other protocol defined exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 41 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pergoveris®<br> | Drug: Pergoveris®<br>* Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 International Unit (IU) recombinant human follicular stimulating hormone (rhFSH)/ 150 IU recombinant human luteinizing hormone (rhLH) after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 millimeter (mm); 250 microgram (mcg) of r-hCG (Ovidrel) was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.<br>* Other names: Follitropin alfa/Lutropin alfa;Drug: Recombinant human chorionic gonadotrophin (r-hCG)<br>* On r-hCG day, 250 mcg of r-hCG was administered once subcutaneously<br>* Other names: choriogonadotropin alfa;|
| Active Comparator: GONAL-f®<br> | Drug: GONAL-f®<br>* GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.<br>* Other names: Follitropin alfa;Drug: Recombinant human chorionic gonadotrophin (r-hCG)<br>* On r-hCG day, 250 mcg of r-hCG was administered once subcutaneously<br>* Other names: choriogonadotropin alfa;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Oocytes Retrieved | Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body. | At approximately 34 to 38 hours after r-hCG administration (Day 113) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing Pregnancy Rate | Ongoing pregnancy rate was defined as the percentage of subjects with a ultrasound confirmation of at least one viable fetus (positive fetal heart beat). | 70 days after embryo transfer (Day 185) | 
| Live Birth Rate | Live birth rate was defined as the percentage of subjects with at least one live-born neonate. | Approximately 180 days following ongoing pregnancy determination (Day 365) | 
| Embryo Implantation Rate | Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100. | 35-42 days post r-hCG administration (Day 154) | 
| Clinical Pregnancy Rate | Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity. | 35-42 days post r-hCG administration (Day 154) | 
| Biochemical Pregnancy Rate | Biochemical pregnancy rate was defined as the percentage of subjects with a positive beta-hCG result from the serum pregnancy test. | 15 to 20 days post r-hCG administration (Day 132) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pergoveris®, ESPART, Reproductive Techniques, Assisted, Infertility, GONAL-f®