Trial Outcomes & Findings for A Randomised Trial Using Highly Purified Human Chorionic Gonadotropin (HP-hCG) and Recombinant Human Chorionic Gonadotropin (rhCG) in Women Undergoing Controlled Ovarian Stimulation (NCT NCT02449889)
NCT ID: NCT02449889
Last Updated: 2019-06-26
Results Overview
Oocyte retrieval took place 36 h (±2h) after hCG administration. At oocyte retrieval the number of oocytes retrieved was recorded.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
176 participants
Primary outcome timeframe
Approximately 36 hours after hCG administration
Results posted on
2019-06-26
Participant Flow
A total of 4 sites in Brazil randomized subjects to the trial.
In total 245 subjects were screened. Of these, 69 were screening failures and 176 were randomized. All randomized subjects were exposed to investigational medicinal product (IMP).
Participant milestones
| Measure |
HP-hCG IM
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Overall Study
STARTED
|
58
|
58
|
60
|
|
Overall Study
COMPLETED
|
57
|
52
|
59
|
|
Overall Study
NOT COMPLETED
|
1
|
6
|
1
|
Reasons for withdrawal
| Measure |
HP-hCG IM
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
0
|
|
Overall Study
Protocol Violation
|
0
|
4
|
1
|
Baseline Characteristics
A Randomised Trial Using Highly Purified Human Chorionic Gonadotropin (HP-hCG) and Recombinant Human Chorionic Gonadotropin (rhCG) in Women Undergoing Controlled Ovarian Stimulation
Baseline characteristics by cohort
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
Total
n=176 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
<35 years
|
35 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
100 Participants
n=4 Participants
|
|
Age, Customized
35-37 years
|
20 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
|
Age, Customized
>=38 years
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
176 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
23 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
49 Participants
n=5 Participants
|
51 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
150 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
Brazil
|
58 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
176 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Approximately 36 hours after hCG administrationPopulation: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
Oocyte retrieval took place 36 h (±2h) after hCG administration. At oocyte retrieval the number of oocytes retrieved was recorded.
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Number of Oocytes Retrieved
|
7.1 Number of oocytes
Standard Deviation 4.6
|
7.3 Number of oocytes
Standard Deviation 4.8
|
6.6 Number of oocytes
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: Prior to insemination (within 6 hours after oocyte retrieval)Population: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment. Note that only subjects with ICSI were included in this analysis, i.e. 58 subjects in the HP-hCG IM group, 55 subjects in the HP-hCG SC group and 57 subjects in the rhCG SC group.
Only applicable for insemination using intracytoplasmic sperm injection (ICSI). The MII oocytes were counted prior to insemination.
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=55 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=57 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Number of Metaphase II (MII) Oocytes
|
5.9 Number of MII oocytes
Standard Deviation 3.7
|
6.2 Number of MII oocytes
Standard Deviation 3.5
|
5.6 Number of MII oocytes
Standard Deviation 3.3
|
SECONDARY outcome
Timeframe: One day after oocyte retrievalPopulation: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
Fertilization was assessed by counting the number of pronuclei, which was recorded as 0, 1, 2 or \>2. Correct fertilization was defined as oocytes with 2PN.
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Number of Fertilized (2 Pronuclei (2PN)) Oocytes
|
4.4 Number of fertilized oocytes
Standard Deviation 3.3
|
4.7 Number of fertilized oocytes
Standard Deviation 3.4
|
4.2 Number of fertilized oocytes
Standard Deviation 2.7
|
SECONDARY outcome
Timeframe: 13-15 days after transferPopulation: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
Defined as percentage of subjects with positive beta hCG. A positive β hCG was confirmed by a blood test obtained 13-15 days after transfer.
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Positive β Unit of Human Chorionic Gonadotropin (βhCG) Rate
|
50.0 percentage of participants
|
37.9 percentage of participants
|
36.7 percentage of participants
|
SECONDARY outcome
Timeframe: 5-6 weeks after transferPopulation: The ITT analysis set was defined as all randomized subjects. Subjects were analyzed according to planned (randomized) treatment.
Defined as percentage of subjects with clinical pregnancy. Clinical pregnancy was defined as at least one gestational sac 5-6 weeks after transfer.
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Clinical Pregnancy Rate
|
46.6 percentage of participants
|
27.6 percentage of participants
|
31.7 percentage of participants
|
SECONDARY outcome
Timeframe: AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presentedPopulation: Safety was summarized based on the safety analysis set.The safety analysis set included all 176 subjects. Subjects were analyzed according to their actual treatment.
The number of treatment-emergent AEs (TEAEs) in each treatment group will be presented.
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Frequency of Adverse Events (AEs)
|
22 Number of AEs
|
25 Number of AEs
|
25 Number of AEs
|
SECONDARY outcome
Timeframe: AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months. However, only TEAEs are presented.Population: Safety was summarized based on the safety analysis set.The safety analysis set included all 176 subjects. Subjects were analyzed according to their actual treatment.
The intensity of an TEAE would be classified using the following 3-point scale: mild (awareness of signs or symptoms, but no disruption of usual activity), moderate (event sufficient to affect usual activity \[disturbing\]) or severe (inability to work or perform usual activities \[unacceptable\]).
Outcome measures
| Measure |
HP-hCG IM
n=58 Participants
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 Participants
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG SC
n=60 Participants
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Intensity of AEs
Any moderate AE
|
8 Participants
|
6 Participants
|
3 Participants
|
|
Intensity of AEs
Any severe AE
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Intensity of AEs
Any mild AE
|
14 Participants
|
18 Participants
|
22 Participants
|
Adverse Events
HP-hCG IM
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
HP-hCG SC
Serious events: 1 serious events
Other events: 12 other events
Deaths: 0 deaths
rhCG
Serious events: 2 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
HP-hCG IM
n=58 participants at risk
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 participants at risk
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG
n=60 participants at risk
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/58 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/60 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Reproductive system and breast disorders
Adnexal torsion
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/60 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
|
1.7%
1/58 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/60 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
Other adverse events
| Measure |
HP-hCG IM
n=58 participants at risk
Highly purified human chorionic gonadotropin 5000 international units (IU), intramuscularly (IM)
Highly purified human chorionic gonadotropin
|
HP-hCG SC
n=58 participants at risk
Highly purified human chorionic gonadotropin, 5000 IU subcutaneously (SC)
Highly purified human chorionic gonadotropin
|
rhCG
n=60 participants at risk
Recombinant human chorionic gonadotropin 250 µg SC
Recombinant human chorionic gonadotropin
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
5.2%
3/58 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/58 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/60 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Nervous system disorders
Headache
|
1.7%
1/58 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
6.9%
4/58 • Number of events 4 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/60 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy
|
3.4%
2/58 • Number of events 2 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
10.3%
6/58 • Number of events 6 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
5.0%
3/60 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/58 • Number of events 1 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
5.0%
3/60 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Haemorrhage in pregnancy
|
3.4%
2/58 • Number of events 2 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
5.2%
3/58 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
1.7%
1/60 • Number of events 2 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Pregnancy, puerperium and perinatal conditions
Vanishing twin syndrome
|
5.2%
3/58 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/60 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
|
Reproductive system and breast disorders
Pelvic pain
|
5.2%
3/58 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
0.00%
0/58 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
5.0%
3/60 • Number of events 3 • AEs were collected from signing informed consent until end of trial visit = maximum period approximately 5 months.
AEs with onset after IMP administration were considered treatment-emergent and are presented for the safety analysis set.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The only disclosure restriction on the Principal Investigator (PI) is that Sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the Sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Sponsor to seek patent protection of the invention.
- Publication restrictions are in place
Restriction type: OTHER