A Phase 2 Trial to Evaluate if Corifollitropin Alfa (Org 36286), Followed by a Low Daily Dose of hCG or Recombinant FSH Can Induce Monofollicular Growth in Women With WHO Group II Anovulatory Infertility (P05693)

• ClinicalTrials.gov Identifier: NCT00697255
• Recruitment Status: Terminated
• First Posted: June 13, 2008
• Results First Posted: June 9, 2014
• Last Update Posted: February 3, 2022
• Sponsor: Organon and Co
• Information provided by (Responsible Party): Organon and Co

Study Description

Brief Summary:

The primary objective of this trial is to evaluate whether a corifollitropin alfa (Org 36286) regimen applying a single or repeated dose of corifollitropin alfa followed by a low daily dose of Human Chorion Gonadotropin (hCG) or recombinant Follicular Stimulating Hormone (recFSH) can induce monofollicular growth (one follicle ≥18 mm and no other follicle ≥15 mm at day of bolus injection of hCG) in women with WHO group II anovulatory infertility.

Condition or disease	Intervention/treatment	Phase
Ovulation Induction	Drug: corifollitropin alfa; Biological: recombinant Follicle Stimulating Hormone (recFSH); Biological: human Chorion Gonadotropin (hCG); Biological: hCG Bolus injection	Phase 2

Detailed Description:

This trial will include two separate stages (Ia+Ib and II).

Stage Ia will be open-label and uncontrolled in a small cohort of women (n=5) to explore whether the intended dosing regimen of corifollitropin alfa followed by daily low dose recFSH provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria.

Stage Ib will be open-label and uncontrolled in a small cohort of women (n=5) to explore whether the intended dosing regimen of corifollitropin alfa followed by daily low dose hCG provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria.

Stage II is open-label and randomized (n=40) to evaluate whether the intended dosing regimen of corifollitropin alfa followed by low dose FSH (n=20) or hCG (n=20) provide an appropriate response in eligible participants meeting all inclusion and none of the exclusion criteria.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Randomized, Controlled, Open-label, Feasibility Trial to Evaluate if a Single or Repeated Dose of Org 36286 (Corifollitropin Alfa) Followed by a Low Daily Dose of Either hCG or Recombinant FSH Can Induce Monofollicular Growth in Women With WHO Group II Anovulatory Infertility
• Actual Study Start Date: May 15, 2007
• Actual Primary Completion Date: April 3, 2008
• Actual Study Completion Date: May 15, 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: corifollitropin alfa + recFSH; Eligible participants will receive a subcutaneous (SC) injection of corifollitropin alfa (Stage 1a: 15mcg, Stage Ib/II: 30 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient, the participant will receive a second or third dose of corifollitropin alfa (Stage 1a: 15 mcg, Stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm, the participant will start daily SC injections with FSH (Stage 1A: 50 IU, Stage II: 75 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.	Drug: corifollitropin alfa; SC corifollitropin alfa on the 1st, 2nd or 3rd day after onset of a progestagen-induced withdrawal bleeding (Stage 1a: 15mcg, Stage Ib/II: 30 mcg).; Other Names: Org 36286; SCH 900962; MK-8962; Biological: recombinant Follicle Stimulating Hormone (recFSH); Daily injections of SC recFSH (50 IU/75 IU) administered as soon as the largest follicle reaches a size ≥12 mm 4 days after a corifollitropin alfa injection on stimulation day 5, 9 or 13.; Other Name: Puregon®; Biological: hCG Bolus injection; Bolus injection of SC hCG was administered to induce final oocyte maturation if at least one follicle is ≥18 mm and no more than two follicles ≥15 mm are observed.; Other Name: Pregnyl®
Experimental: corifollitropin alfa + hCG; Eligible participants will receive a SC injection of corifollitropin alfa (Stage Ia:15 mcg, Stage Ib/II: 30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth is insufficient the participant will receive a second or third dose of corifollitropin alfa (Stage IA: 15 mcg, stage Ib/II: 20 mcg). As soon as the largest follicle reaches a size of ≥12 mm the participant will start daily SC injections with hCG (Stage Ib/II: 200 IU) the same day. A bolus injection of hCG (5000 IU) will be administered if at least one follicle is ≥18 mm and in total no more than two follicles ≥15 mm are observed.	Drug: corifollitropin alfa; SC corifollitropin alfa on the 1st, 2nd or 3rd day after onset of a progestagen-induced withdrawal bleeding (Stage 1a: 15mcg, Stage Ib/II: 30 mcg).; Other Names: Org 36286; SCH 900962; MK-8962; Biological: human Chorion Gonadotropin (hCG); Daily injections of SC hCG (200 IU) administered as soon as the largest follicle reaches a size ≥12 mm 4 days after a corifollitropin alfa injection on stimulation day 5, 9 or 13.; Other Name: Pregnyl®; Biological: hCG Bolus injection; Bolus injection of SC hCG was administered to induce final oocyte maturation if at least one follicle is ≥18 mm and no more than two follicles ≥15 mm are observed.; Other Name: Pregnyl®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Monofollicular Response (Monofollicular Rate) [ Time Frame: At day of bolus injection of hCG (up to 20 days) ]
   The monofollicular rate was defined as the number of participants with monofollicular response (one follicle ≥18 mm and no other follicle ≥15 mm on the day of the bolus injection of hCG) divided by the number of the treated participants.

Secondary Outcome Measures :

1. Percentage of Participants With Ovulation (Ovulation Rate) [ Time Frame: 8 days after bolus injection of hCG (up to 28 days) ]
   Ovulation rate was defined as the number of participants with confirmed ovulation (≥15 nmol/l serum progesterone eight days after the bolus injection of hCG) divided by the number of treated participants. Ovulation was also considered confirmed for participants who became pregnant, had an ectopic pregnancy or had a miscarriage.
2. Percentage of Participants With Monofollicular Ovulation (Monofollicular Ovulation Rate) [ Time Frame: 8 days after bolus injection of hCG (up to 28 days) ]
   Monofollicular ovulation rate was defined as the number of participants with monofollicular response (one follicle ≥18 mm and no other follicle ≥15 mm on the day of the bolus injection of hCG) and confirmed ovulation (≥15 nmol/l serum progesterone eight days after the bolus injection of hCG) divided by the number of treated participants. Ovulation was also considered confirmed for participants who became pregnant, had an ectopic pregnancy or had a miscarriage.
3. Percentage of Participants Who Cancelled Treatment (Cancellation Rate) [ Time Frame: Up to 3 weeks after bolus injection of hCG (up to 41 days) ]
   Treatment was considered cancelled if no bolus injection of hCG was administrated. Reasons of treatment failure included Adverse Event (AE)/ Serious Adverse Event (SAE), insufficient ovarian response on stimulation day 13 (no follicle ≥12 mm), insufficient ovarian response after 7 days of hCG/recFSH treatment (no follicle ≥18 mm), and multifollicular growth (≥3 follicles ≥15 mm).
4. Number of Participants With Pregnancy [ Time Frame: At least 10 weeks after bolus injection of hCG (up to 13 weeks) ]
   A pregnancy test (serum or urinary hCG) was performed two to three weeks after bolus injection of hCG. In case of a positive pregnancy test vaginal and/or abdominal ultrasound scan was performed to confirm the pregnancy at 5 to 6 weeks after bolus injection of hCG and ≥10 weeks after bolus injection of hCG to confirm ongoing pregnancy.
5. Number of Participants With AEs of Ovarian Hyperstimulation Syndrome (OHSS) [ Time Frame: During In-Treatment Period (up to 14 weeks after first corifollitropin injection) ]
   OHSS was classified on study based on a slightly modified WHO Scientific Group (1973) classification: Grade I (mild) = characterized by excessive steroid secretion and ovarian enlargement (5-7 cm). Abdominal discomfort, including abdominal pain, is present. Grade II (moderate) = characterized by distinct ovarian cysts (ovary size 8-10 cm), accompanied by abdominal pain and tension, nausea, vomiting, diarrhea. Grade III (severe) = characterized by enlarged cystic ovaries (ovary size >10 cm), accompanied by ascites and occasionally hydrothorax. Abdominal tension and pain may be severe. Pronounced hydrothorax together with an abdominal cavity filled with cysts and fluid elevating the diaphragm may cause severe breathing difficulties. Large quantities of fluid inside the cysts and in the peritoneal and pleural cavities cause haemoconcentration and increased blood viscosity. In rare cases, the syndrome may further be complicated by the occurrence of thromboembolic phenomena.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 39 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Oligomenorrhea (average cycle length ≥35 days and <6 months)
• Amenorrhea (average cycle length ≥6 months)
• Body Mass Index ≥18 and ≤30 kg/m^2
• Normal serum FSH levels and normal estradiol levels at screening
• Progestagen induced withdrawal bleeding
• Age ≥18 years and ≤39 years at the time of signing informed consent
• Willing and able to sign informed consent

Exclusion Criteria:

• History of or current ovarian cysts or enlarged ovaries not related to polycystic ovarian syndrome (PCOS)
• History of or current tumors of the ovary, breast, uterus, pituitary or

hypothalamus

• Less than 2 ovaries
• Undiagnosed vaginal bleeding
• Any ovarian and/or abdominal abnormality interfering with ultrasound

examination

• Malformations of the sexual organs incompatible with pregnancy
• Pregnancy or lactation
• Abnormal serum endocrinology levels based on screening sample
• Any clinically relevant abnormal laboratory value based on screening sample
• Alcohol or drug abuse within the 12 months preceding signing of informed consent
• Hypersensitivity to any of the substances in corifollitropin alfa
• Hypersensitivity to hCG/ Puregon® or any of its components
• Previous use of corifollitropin alfa
• Use of any investigational drug during 90 days before screening

Contacts and Locations

No Contacts or Locations Provided

More Information

Study Data/Documents: CSR Synopsis 

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00697255
• Other Study ID Numbers: P05693; 2006-000705-30 ( EudraCT Number ); 107010 ( Other Identifier: Organon ); MK-8962-002 ( Other Identifier: Merck )
• First Posted: June 13, 2008
• Results First Posted: June 9, 2014
• Last Update Posted: February 3, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Keywords provided by Organon and Co:

Pharmacological effects of drugs; Hormones; Hormone Substitutes and Hormone Antagonists; Pharmacological Actions; Monofollicular growth; Randomized; Open-label; Active-controlled

Additional relevant MeSH terms:

Infertility; Chorionic Gonadotropin; Hormones; Follicle Stimulating Hormone; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Reproductive Control Agents