Corifollitropin Alfa in Participants Undergoing Repeated Controlled Ovarian Stimulation (COS) Cycles Using a Multiple Dose Gonadatropin Releasing Hormone (GnRH) Antagonist Protocol (Study 38825)(P05714) (Trust)

Organon

Status and phase: Completed; Phase 3

Conditions: In Vitro Fertilization

Treatments: Drug: Progesterone; Biological: GnRH antagonist; Biological: FSH; Biological: (rec)hCG; Drug: Corifollitropin alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT00696878

38825 (Other Identifier)

P05714

2004-004966-34 (EudraCT Number)

MK-8962-007 (Other Identifier)

Details and patient eligibility

About

The objective of the trial is to assess the non-immunogenicity and safety of corifollitropin alfa (also known as Org 36286, SCH 900962 and MK-8962) in participants undergoing repeated COS cycles using a multiple dose GnRH antagonist protocol.

Full description

This trial is designed as an open-label, uncontrolled, repeated cycle trial to assess the non-immunogenicity and safety of corifollitropin alfa in participants undergoing repeated COS cycles for in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) using a multiple dose GnRH antagonist protocol. The trial period per participant will cover 1, 2 or 3 COS treatment cycles and no more than three (in-between two stimulation cycles) Frozen-Thawed Embryo Transfer (FTET) cycles following either or both of the first two treatment cycles. In each stimulation cycle, participants receive a single injection of corifollitropin alfa and one week later, treatment is continued with a daily dose of any FSH-containing preparation up to the day of (rec)hCG administration for final oocyte maturation. Assessment of anti-corifollitropin alfa antibodies and local tolerance after corifollitropin alfa injection are important safety endpoints in this trial.

Enrollment: 682 patients

Sex: Female

Ages: 18 to 39 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females of couples with an indication for COS and IVF or ICSI;
• >=18 and <=39 years of age at the time of signing informed consent;
• Body weight > 60 kg and body mass index (BMI) >=18 and <=29 kg/m^2;
• Normal menstrual cycle length: 24-35 days;
• Availability of ejaculatory sperm (use of donated and/or cryopreserved sperm is allowed);
• Willing and able to sign informed consent.

Exclusion criteria

• History of or any current (treated) endocrine abnormality;
• History of ovarian hyper-response or history of ovarian hyperstimulation syndrome (OHSS);
• History of or current polycystic ovary syndrome (PCOS);
• More than 20 basal antral follicles (size: <11 mm, both ovaries combined) as measured on USS in the early follicular phase (menstrual cycle day 2-5);
• Less than 2 ovaries or any other ovarian abnormality, including endometrioma >10 mm (visible on USS);
• Presence of unilateral or bilateral hydrosalpinx (visible on USS);
• More than three unsuccessful COS cycles since the last established ongoing pregnancy (if applicable);
• History of non- or low ovarian response to FSH/human menopausal gonadotrophin (hMG) treatment;
• FSH > 12 IU/L or luteinizing hormone (LH) > 12 IU/L as measured by the local laboratory (sample taken during the early follicular phase: menstrual cycle day 2-5);
• Any clinically relevant abnormal laboratory value based on a sample taken during the screening phase, including abnormal cervical smear (Papanicolaou [PAP]>=III, cervical intraepithelial neoplasia [CIN]>=1);
• Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts) or GnRH antagonists (e.g. hypersensitivity, pregnancy/lactation);
• Recent history of or current epilepsy, human immunodeficiency virus (HIV) infection, thrombophilia, diabetes or cardiovascular, gastro-intestinal, hepatic, renal, or pulmonary disease;
• Abnormal karyotyping of the participant or her partner (if karyotyping is performed);
• History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
• Previous use of corifollitropin alfa;
• Use of hormonal preparations within 1 month prior to screening;
• Administration of investigational drugs within three months prior to signing informed consent.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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682 participants in 1 patient group

Corifollitropin alfa 150 µg

Experimental group

Description:

Up to 3 COS cycles (also called treatment cycles) were performed, each including the following: A single injection of 150 µg corifollitropin alfa was administered on Day 2 or 3 of the menstrual cycle (Stimulation Day 1). Administration of GnRH antagonist (0.25 mg/day) started on Stimulation Day 5 or 6 and continued through day of administration of recombinant Human Chorion Gonadotropin (\[rec\]hCG) (5,000-10,000 IU/250 µg). Administration of (rec)hCG occurred when 3 follicles ≥17 mm were observed on ultrasound scan (USS). Daily dosing with Follicle Stimulating Hormone (FSH) (not to exceed 225 IU/day) began on Stimulation Day 8 and continued up to day of (rec)hCG administration. Progesterone for luteal phase support was administered starting on the day of oocyte pick-up (34-36 hours after \[rec\]hCG) and continued for approximately 6 weeks. After COS cycles 1 and 2, Frozen-Thawed Embryo Transfer cycles (up to 3 after each COS cycle) could occur.

Treatment:

Biological: (rec)hCG

Drug: Corifollitropin alfa

Biological: FSH

Biological: GnRH antagonist

Drug: Progesterone