Trial Outcomes & Findings for 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) (NCT NCT00697255)
NCT ID: NCT00697255
Last Updated: 2024-06-17
Results Overview
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.
TERMINATED
PHASE2
8 participants
At day of bolus injection of hCG (up to 20 days)
2024-06-17
Participant Flow
5 participants were enrolled in Stage 1a to receive corifollitropin alfa + recombinant Follicular Stimulating Hormone (recFSH), and 3 participants were enrolled in Stage 1b to receive corifollitropin alfa + Human Chorion Gonadotropin (hCG).
Participant milestones
| Measure |
Corifollitropin Alfa + recFSH
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Stage 1a
STARTED
|
5
|
0
|
|
Stage 1a
COMPLETED
|
2
|
0
|
|
Stage 1a
NOT COMPLETED
|
3
|
0
|
|
Stage 1b
STARTED
|
0
|
3
|
|
Stage 1b
COMPLETED
|
0
|
1
|
|
Stage 1b
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
| Measure |
Corifollitropin Alfa + recFSH
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Stage 1a
Insufficient ovarian response
|
1
|
0
|
|
Stage 1a
Multifollicular growth
|
1
|
0
|
|
Stage 1a
Not growing of dominant follicle
|
1
|
0
|
|
Stage 1b
Not growing of dominant follicle
|
0
|
1
|
|
Stage 1b
Insufficient ovarian response
|
0
|
1
|
Baseline Characteristics
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)
Baseline characteristics by cohort
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Total
n=8 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30.8 years
STANDARD_DEVIATION 5.9 • n=5 Participants
|
28.7 years
STANDARD_DEVIATION 2.5 • n=7 Participants
|
30.0 years
STANDARD_DEVIATION 4.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At day of bolus injection of hCG (up to 20 days)Population: Intent-to-Treat group (ITT) consisted of all treated participants (5 participants in Stage Ia and 3 participants in Stage Ib).
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.
Outcome measures
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Percentage of Participants With Monofollicular Response (Monofollicular Rate)
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: 8 days after bolus injection of hCG (up to 28 days)Population: Intent-to-Treat group (ITT) consisted of all treated participants (5 participants in Stage Ia and 3 participants in Stage Ib).
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.
Outcome measures
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Percentage of Participants With Ovulation (Ovulation Rate)
|
40.0 percentage of participants
|
33.3 percentage of participants
|
SECONDARY outcome
Timeframe: 8 days after bolus injection of hCG (up to 28 days)Population: Intent-to-Treat group (ITT) consisted of all treated participants (5 participants in Stage Ia and 3 participants in Stage Ib).
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.
Outcome measures
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Percentage of Participants With Monofollicular Ovulation (Monofollicular Ovulation Rate)
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Up to 3 weeks after bolus injection of hCG (up to 41 days)Population: Intent-to-Treat group (ITT) consisted of all treated participants (5 participants in Stage Ia and 3 participants in Stage Ib).
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).
Outcome measures
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Percentage of Participants Who Cancelled Treatment (Cancellation Rate)
Insufficient ovarian response
|
20.0 percentage of participants
|
33.3 percentage of participants
|
|
Percentage of Participants Who Cancelled Treatment (Cancellation Rate)
Multifollicular growth
|
20.0 percentage of participants
|
0 percentage of participants
|
|
Percentage of Participants Who Cancelled Treatment (Cancellation Rate)
Not growing of dominant follicle
|
20.0 percentage of participants
|
33.3 percentage of participants
|
SECONDARY outcome
Timeframe: At least 10 weeks after bolus injection of hCG (up to 13 weeks)Population: Intent-to-Treat group (ITT) consisted of all treated participants (5 participants in Stage Ia and 3 participants in Stage Ib).
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.
Outcome measures
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Number of Participants With Pregnancy
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: During In-Treatment Period (up to 14 weeks after first corifollitropin injection)Population: The All-Participants-Treated (APT) group consisted of all participants who received corifollitropin alfa. Participants were grouped according to the stage of the trial and the active treatment group (recFSH Stage Ia, hCG Stage Ib) they actually received.
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.
Outcome measures
| Measure |
Corifollitropin Alfa + recFSH
n=5 Participants
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 Participants
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Number of Participants With AEs of Ovarian Hyperstimulation Syndrome (OHSS)
|
0 participants
|
0 participants
|
Adverse Events
Corifollitropin Alfa + recFSH
Corifollitropin Alfa + hCG
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Corifollitropin Alfa + recFSH
n=5 participants at risk
Eligible participants in Stage 1a received a subcutaneous (SC) injection of corifollitropin alfa (15 mcg) the first, second, or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient, the participant received a second or third dose of corifollitropin alfa (15 mcg). As soon as the largest follicle reached a size of ≥12 mm, the participant started daily SC injections with recFSH (50 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
Corifollitropin Alfa + hCG
n=3 participants at risk
Eligible participants in Stage 1b received a SC injection of corifollitropin alfa (30 mcg) the first, second or third day after onset of a progestagen-induced withdrawal bleeding. If the follicle growth was insufficient the participant received a second or third dose of corifollitropin alfa (20 mcg). As soon as the largest follicle reached a size of ≥12 mm the participant started daily SC injections with hCG (200 IU) the same day. A bolus injection of hCG (5000 IU) was administered if at least one follicle was ≥18 mm and in total no more than two follicles ≥15 mm were observed.
|
|---|---|---|
|
Psychiatric disorders
Listless
|
20.0%
1/5 • Number of events 1 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
0.00%
0/3 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
|
Nervous system disorders
Headache
|
0.00%
0/5 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
33.3%
1/3 • Number of events 1 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
|
Vascular disorders
Hypertension
|
0.00%
0/5 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
33.3%
1/3 • Number of events 1 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
|
Gastrointestinal disorders
Nausea
|
20.0%
1/5 • Number of events 1 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
33.3%
1/3 • Number of events 1 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
|
General disorders
Fatigue
|
20.0%
1/5 • Number of events 1 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
0.00%
0/3 • During In-Treatment Period (up to 14 weeks after first corifollitropin injection)
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Results disclosure agreements
- Principal investigator is a sponsor employee All publications must be based on data validated and released by the Sponsor. Any such scientific paper, presentation, or other communication concerning the clinical trial described in the protocol will first be submitted to the Sponsor, at least 6 weeks ahead of estimated publication or presentation, for written consent, which shall not be withheld unreasonably.
- Publication restrictions are in place
Restriction type: OTHER