A Phase III, Uncontrolled Trial to Assess the Non-immunogenicity and Safety of Org 36286 in Patients Undergoing Repeated Controlled Ovarian Stimulation Cycles Using a Multiple Dose GnRH Antagonist Protocol

Organon and Co0 个研究点目标入组 682 人开始时间: 2006年9月26日最近更新: 2024年6月18日

适应症

干预措施

试验速览

阶段: 3 期
状态: 已完成
发起方: Organon and Co
入组人数: 682
主要终点: Number of Participants With Serious AEs (SAEs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者记录与标识符相似试验

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 39 Years（Adult）
性别: Female
接受健康志愿者: 否

入选标准

•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.

排除标准

•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.

研究组 & 干预措施

Corifollitropin alfa 150 µg

Experimental

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.

干预措施: Corifollitropin alfa (Drug)

Corifollitropin alfa 150 µg

Experimental

干预措施: FSH (Biological)

Corifollitropin alfa 150 µg

Experimental

干预措施: GnRH antagonist (Biological)

Corifollitropin alfa 150 µg

Experimental

干预措施: (rec)hCG (Biological)

Corifollitropin alfa 150 µg

Experimental

干预措施: Progesterone (Drug)

结局指标

主要结局

Number of Participants With Serious AEs (SAEs)

时间窗: Up to approximately 26 months after first dose of corifollitropin alfa

An SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. SAEs that occurred in fetuses or infants during the study period are included in this summary of SAEs, and are allocated to the associated study participant who was administered corifollitropin alfa.

Percentage of Participants With Clinically Relevant Immunogenicity

时间窗: Pre-dose (Stimulation Day 1) and up to approximately 40 days post dose in each treatment cycle

Serum samples obtained pre-dose and at 2 weeks after embryo transfer (ET), or at cycle discontinuation and 2-3 weeks after cycle discontinuation if cycle was stopped before ET was performed, were analyzed for presence of anti-corifollitropin alfa antibodies using screening and confirmatory tests. If a participant was confirmed to have anti-corifollitropin alfa antibody present in a post dose sample according to these tests, review of adverse events (AEs) in the participant was performed. The sample was also tested to evaluate whether the antibody appeared to have neutralizing activity that would interfere with the study drug biological effect. A participant was determined to have clinically relevant immunogenicity if the participant had a confirmed post dose anti-corifollitropin alfa antibody test result accompanied by clinical signs of immunogenicity (e.g., hypersensitivity reaction), considering also the results of the test for neutralizing activity of any antibody present.

Local Tolerance at Injection Site: Number of Participants With no Event of Itching and With Mild, Moderate and Severe Itching in Any of 3 Treatment Cycles