Back to resultsA 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)
Primary Purpose
Ovulation Induction
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
corifollitropin alfa
recombinant Follicle Stimulating Hormone (recFSH)
human Chorion Gonadotropin (hCG)
hCG Bolus injection
Sponsored by
About this trial
This is an interventional treatment trial for Ovulation Induction focused on measuring Pharmacological effects of drugs, Hormones, Hormone Substitutes and Hormone Antagonists, Pharmacological Actions, Monofollicular growth, Randomized, Open-label, Active-controlled
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
corifollitropin alfa + recFSH
corifollitropin alfa + hCG
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Percentage of Participants With Monofollicular Response (Monofollicular Rate)
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
Percentage of Participants With Ovulation (Ovulation Rate)
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.
Percentage of Participants With Monofollicular Ovulation (Monofollicular Ovulation Rate)
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.
Percentage of Participants Who Cancelled Treatment (Cancellation Rate)
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).
Number of Participants With Pregnancy
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.
Number of Participants With AEs of Ovarian Hyperstimulation Syndrome (OHSS)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00697255
Brief Title
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)
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Terminated
Study Start Date
May 15, 2007 (Actual)
Primary Completion Date
April 3, 2008 (Actual)
Study Completion Date
May 15, 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovulation Induction
Keywords
Pharmacological effects of drugs, Hormones, Hormone Substitutes and Hormone Antagonists, Pharmacological Actions, Monofollicular growth, Randomized, Open-label, Active-controlled
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
corifollitropin alfa + recFSH
Arm Type
Experimental
Arm Description
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.
Arm Title
corifollitropin alfa + hCG
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
corifollitropin alfa
Other Intervention Name(s)
Org 36286, SCH 900962, MK-8962
Intervention Description
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).
Intervention Type
Biological
Intervention Name(s)
recombinant Follicle Stimulating Hormone (recFSH)
Other Intervention Name(s)
Puregon®
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
human Chorion Gonadotropin (hCG)
Other Intervention Name(s)
Pregnyl®
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
hCG Bolus injection
Other Intervention Name(s)
Pregnyl®
Intervention Description
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.
Primary Outcome Measure Information:
Title
Percentage of Participants With Monofollicular Response (Monofollicular Rate)
Description
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.
Time Frame
At day of bolus injection of hCG (up to 20 days)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Ovulation (Ovulation Rate)
Description
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.
Time Frame
8 days after bolus injection of hCG (up to 28 days)
Title
Percentage of Participants With Monofollicular Ovulation (Monofollicular Ovulation Rate)
Description
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.
Time Frame
8 days after bolus injection of hCG (up to 28 days)
Title
Percentage of Participants Who Cancelled Treatment (Cancellation Rate)
Description
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).
Time Frame
Up to 3 weeks after bolus injection of hCG (up to 41 days)
Title
Number of Participants With Pregnancy
Description
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.
Time Frame
At least 10 weeks after bolus injection of hCG (up to 13 weeks)
Title
Number of Participants With AEs of Ovarian Hyperstimulation Syndrome (OHSS)
Description
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.
Time Frame
During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
Eligibility 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
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Available IPD and Supporting Information:
Available IPD/Information Type
CSR Synopsis
Available IPD/Information URL
http://www.merck.com/clinical-trials/study.html?id=P05693&kw=P05693&tab=access
Learn more about this trial
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)
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