Clinical trial NCT00702845: To Investigate Efficacy and Safety of a Single Injection of Org 36286 for Ovarian Stimulation Using Daily Recombinant FSH as Reference (Ensure)(P05690/MK-8962-001)
Official title: A Phase III, Randomized, Double-blind, Active-controlled, Equivalence Clinical Trial to Investigate the Efficacy and Safety of a Single Injection of 100 µg Org 36286 (Corifollitropin Alfa) to Induce Multifollicular Development for Controlled Ovarian Stimulation (COS) Using Daily Recombinant FSH (recFSH) as a Reference
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infertility
Keywords: In vitro fertilization
Pharmacological effects of drugs
Hormones
Hormone Substitutes and Hormone Antagonists
Pharmacological Actions
Randomized
Multi-center
Multi-national
Double-blind
Active-controlled
Equivalence
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2008-06-20
Enrollment: 397
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 36
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Clinical trial objectives are to investigate the efficacy and safety of a single injection of 100 μg Org 36286 in women weighing 60 kg or less to induce multifollicular development for controlled ovarian stimulation (COS), using daily recFSH as a reference.

Detailed description: This is a randomized, double-blind, active-controlled, equivalence clinical trial investigating the efficacy and safety of a new treatment regimen with Org 36286, a recombinant gonadotropin applied to initiate and sustain follicular stimulation in COS for Assisted Reproductive Technology (ART). For this regimen, patients receive a single injection of Org 36286 and one week later, treatment is continued with daily recFSH up to the day of triggering final oocyte maturation. In the reference group patients receive daily injections of recFSH up to the day of triggering final oocyte maturation. Equivalence between the two treatment groups in the number of oocytes retrieved is the primary objective of this trial.

Eligibility criteria: Inclusion Criteria:

* Females of couples with an indication for COS and IVF or ICSI;
* \>=18 and \<= 36 years of age at the time of signing informed consent;
* Body weight \<= 60 kg and BMI \>= 18 and \<= 32 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 ovarian hyperstimulation syndrome

(OHSS);

* History of/or current polycystic ovary syndrome (PCOS);
* More than 20 basal antral follicles \<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 hydrosalphinx (visible on USS);
* Presence of any clinically relevant pathology affecting the uterine cavity or fibroids \>= 5 cm;
* More than three unsuccessful IVF cycles since the last established ongoing

pregnancy (if applicable);

* History of non- or low ovarian response to FSH/hMG treatment;
* History of recurrent miscarriage (3 or more, even when unexplained);
* FSH \> 12 IU/L or 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;
* Contraindications for the use of gonadotropins (e.g. tumors, pregnancy/lactation, undiagnosed vaginal bleeding, hypersensitivity, ovarian cysts);
* Recent history of/or current epilepsy, HIV infection, diabetes, cardiovascular,

gastro-intestinal, hepatic, renal or pulmonary disease;

* Abnormal karyotyping of the patient or her partner (if karyotyping is performed);
* Smoking more than 5 cigarettes per day;
* History or presence of alcohol or drug abuse within 12 months prior to signing informed consent;
* Previous use of Org 36286;
* Use of hormonal preparations within 1 month prior to randomization;
* Hypersensitivity to any of the concomitant medication prescribed as part of the treatment regimen in this protocol;
* Administration of investigational drugs within three months prior to signing informed consent.

Primary outcomes:
measure: Number of Cumulus-oocyte-complexes Retrieved, Per Attempt
timeFrame: One COS cycle with cumulus-oocyte-complex retrieval (up to a maximum total duration of 21 days)
Secondary outcomes:
measure: Total Dose of recFSH Administered
timeFrame: One COS cycle (up to a maximum total duration of 19 stimulation days)
measure: Total Dose of recFSH Administered From Day 8 Onwards
timeFrame: Stimulation Day 8 of COS cycle up to day of hCG administration (up to a maximum total duration of 19 stimulation days)
measure: Number of Days Treated With recFSH
timeFrame: One COS cycle (up to a maximum total duration of 19 stimulation days)
measure: Total Duration of Stimulation (Days)
timeFrame: One COS cycle (up to a maximum total duration of 19 stimulation days)
measure: Serum Follicle Stimulating Hormone (FSH) Levels (Restricted to Participants With hCG Injection)
timeFrame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
measure: Serum Lutenizing Hormone (LH) Levels (Restricted to Participants With hCG Injection)
timeFrame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
measure: Serum Estradiol (E2) Levels (Restricted to Participants With hCG Injection)
timeFrame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
measure: Serum Progesterone (P) Levels (Restricted to Participants With hCG Injection)
timeFrame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
measure: Serum Inhibin-B Levels (Restricted to Participants With hCG Injection)
timeFrame: Predose up to 2 weeks after ET (up to maximum of 6 weeks)
measure: Number and Size Distribution of Follicles During Stimulation and on the Day of hCG Administration
timeFrame: Predose up to day of hCG administration (up to a maximum total duration of 19 stimulation days, including day of hCG administration)
measure: Number and Quality of Oocytes Assessed Prior to ICSI (Restricted to Participants With ICSI Only)
timeFrame: Up to 36 hours after administration of hCG
measure: Fertilization Rate
timeFrame: Up to 10 weeks after ET
measure: Number and Quality of Embryos Obtained at Day 3 (Restricted to Participants With IVF and/or ICSI)
timeFrame: Post fertilization Day 3 (up to a maximum of 2 days after hCG administration)
measure: Implantation Rate for Participants With ET
timeFrame: Up to 6 weeks after ET within a treatment cycle (up to a maximum 10 weeks)
measure: Number of Participants With Miscarriages
timeFrame: Up to 10 weeks after ET (up to a maximum of 14 weeks)
measure: Number of Participants With Pregnancies
timeFrame: Up to 10 weeks after ET (up to a maximum of 14 weeks)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Corifollitropin alfa Ensure Study Group. Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod Biomed Online. 2010 Jul;21(1):66-76. doi: 10.1016/j.rbmo.2010.03.019. Epub 2010 Mar 28.
citation: Zandvliet AS, Prohn M, de Greef R, van Aarle F, McCrary Sisk C, Stegmann BJ. Impact of patient characteristics on the pharmacokinetics of corifollitropin alfa during controlled ovarian stimulation. Br J Clin Pharmacol. 2016 Jul;82(1):74-82. doi: 10.1111/bcp.12939. Epub 2016 May 31.
citation: Griesinger G, Verweij PJ, Gates D, Devroey P, Gordon K, Stegmann BJ, Tarlatzis BC. Prediction of Ovarian Hyperstimulation Syndrome in Patients Treated with Corifollitropin alfa or rFSH in a GnRH Antagonist Protocol. PLoS One. 2016 Mar 7;11(3):e0149615. doi: 10.1371/journal.pone.0149615. eCollection 2016.