Trial Outcomes & Findings for Phase 3 Study to Evaluate the Efficacy and Safety of Pergoveris® in Assisted Reproductive Technology (ESPART) (NCT NCT02047227)

NCT ID: NCT02047227

Last Updated: 2017-08-24

Results Overview

Mean number of oocytes retrieved on the day of ovum pick up (OPU) was calculated. Oocyte retrieval was a technique used in in-vitro fertilization in order to remove oocytes from the ovary of the female, enabling fertilization outside the body.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

939 participants

Primary outcome timeframe

At approximately 34 to 38 hours after r-hCG administration (Day 113)

Results posted on

2017-08-24

Participant Flow

The study was conducted at 101 sites in 15 countries.

Participant milestones

Participant milestones
Measure	Pergoveris Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 International Unit (IU) recombinant human follicular stimulating hormone (rhFSH)/ 150 IU recombinant human luteinizing hormone (rhLH) after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 millimeter (mm); 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) (Ovidrel) was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Overall Study STARTED	462	477
Overall Study Completed Ovarian Stimulation Phase	424	440
Overall Study COMPLETED	318	347
Overall Study NOT COMPLETED	144	130

Reasons for withdrawal

Reasons for withdrawal
Measure	Pergoveris Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 International Unit (IU) recombinant human follicular stimulating hormone (rhFSH)/ 150 IU recombinant human luteinizing hormone (rhLH) after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 millimeter (mm); 250 microgram (mcg) of recombinant human chorionic gonadotrophin (r-hCG) (Ovidrel) was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Overall Study Adverse Event	2	4
Overall Study Lost to Follow-up	0	3
Overall Study Protocol Violation	1	0
Overall Study Spontaneous pregnancy	1	0
Overall Study Lack of ovarian response to stimulation	35	32
Overall Study No oocytes retrieved	21	20
Overall Study No fertilization	61	51
Overall Study Intention to freeze all embryos	1	0
Overall Study All embryos discarded	12	11
Overall Study Other	10	9

Baseline Characteristics

Phase 3 Study to Evaluate the Efficacy and Safety of Pergoveris® in Assisted Reproductive Technology (ESPART)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pergoveris n=462 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.	Total n=939 Participants Total of all reporting groups
Age, Continuous	38.3 years STANDARD_DEVIATION 2.9 • n=5 Participants	38.3 years STANDARD_DEVIATION 3.0 • n=7 Participants	38.3 years STANDARD_DEVIATION 3.0 • n=5 Participants
Sex: Female, Male Female	462 Participants n=5 Participants	477 Participants n=7 Participants	939 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 approximately 34 to 38 hours after r-hCG administration (Day 113)

Population: Intent-to-treat (ITT) analysis set included all subjects randomized who received at least 1 dose of GONAL-f or Pergoveris.

Outcome measures

Outcome measures
Measure	Pergoveris n=462 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Number of Oocytes Retrieved	3.3 oocytes Standard Deviation 2.71	3.6 oocytes Standard Deviation 2.82

SECONDARY outcome

Timeframe: 70 days after embryo transfer (Day 185)

Population: Modified intent-to-treat (MITT) analysis set included all randomized subjects who received at least 1 dose of GONAL-f or Pergoveris and did not have spontaneous pregnancy or death at approximately 34-38 hours after rhCG administration.

Ongoing pregnancy rate was defined as the percentage of subjects with a ultrasound confirmation of at least one viable fetus (positive fetal heart beat).

Outcome measures

Outcome measures
Measure	Pergoveris n=462 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Ongoing Pregnancy Rate	11.0 percentage of subjects	12.4 percentage of subjects

SECONDARY outcome

Timeframe: Approximately 180 days following ongoing pregnancy determination (Day 365)

Live birth rate was defined as the percentage of subjects with at least one live-born neonate.

Outcome measures

Outcome measures
Measure	Pergoveris n=462 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Live Birth Rate	10.6 percentage of subjects	11.7 percentage of subjects

SECONDARY outcome

Timeframe: 35-42 days post r-hCG administration (Day 154)

Population: MITT analysis set included all randomized subjects who received at least 1 dose of GONAL-f or Pergoveris and did not have spontaneous pregnancy or death at approximately 34-38 hours after rhCG administration. Here "Number of subjects analyzed" signifies those subjects who were evaluable for this outcome measure.

Embryo implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred multiplied by 100.

Outcome measures

Outcome measures
Measure	Pergoveris n=319 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=349 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Embryo Implantation Rate	14.7 percent sacs per embryo	15.6 percent sacs per embryo

SECONDARY outcome

Timeframe: 35-42 days post r-hCG administration (Day 154)

Clinical pregnancy rate defined as the percentage of subjects with a ultrasound confirmation of a gestational sac, with or without fetal heart activity.

Outcome measures

Outcome measures
Measure	Pergoveris n=462 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Clinical Pregnancy Rate	14.1 percentage of subjects	16.8 percentage of subjects

SECONDARY outcome

Timeframe: 15 to 20 days post r-hCG administration (Day 132)

Population: MITT Analysis Set included all randomized subjects who received at least 1 dose of GONAL-f or Pergoveris and did not have spontaneous pregnancy or death at approximately 34-38 hours after rhCG administration.

Biochemical pregnancy rate was defined as the percentage of subjects with a positive beta-hCG result from the serum pregnancy test.

Outcome measures

Outcome measures
Measure	Pergoveris n=462 Participants Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 Participants GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Biochemical Pregnancy Rate	17.3 percentage of subjects	23.9 percentage of subjects

Adverse Events

Pergoveris

Serious events: 8 serious events

Other events: 111 other events

Deaths: 0 deaths

GONAL-f

Serious events: 17 serious events

Other events: 151 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Merck KGaA Communication Center

Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pergoveris n=462 participants at risk Pergoveris (follitropin alfa and lutropin alfa) was administered subcutaneously once daily with a starting dose of 300 IU rhFSH/150 IU rhLH after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments while maintaining the 2:1 ratio of r hFSH to r-hLH in the Pergoveris group based on the subject's response per site standard clinical practice.	GONAL-f n=477 participants at risk GONAL-f (r-hFSH) was self-administered subcutaneously once daily at a starting dose of 300 IU after confirmation of down regulation up to 21 days. After follicle attained mean diameter of 17-18 mm; 250 mcg of r-hCG was administered once subcutaneously to trigger final follicular maturation as per site standard practice. The dose adjustment for r-hFSH was allowed in 75 IU increments based on the subject's response per site standard clinical practice.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.63% 3/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Abortion	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.42% 2/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Premature labour	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Foetal death	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Hyperemesis gravidarum	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Imminent abortion	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Premature baby	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Premature delivery	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Pregnancy, puerperium and perinatal conditions Threatened labour	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Reproductive system and breast disorders Ovarian cyst	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Reproductive system and breast disorders Ovarian cyst ruptured	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Reproductive system and breast disorders Ovarian haemorrhage	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Reproductive system and breast disorders Ovarian rupture	0.22% 1/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.00% 0/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Congenital, familial and genetic disorders Fallot's tetralogy	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Congenital, familial and genetic disorders Trisomy 21	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Cardiac disorders Ventricular extrasystoles	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Injury, poisoning and procedural complications Overdose	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/462 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)	0.21% 1/477 • Baseline up to 180 days after ongoing pregnancy (maximum up to 365 days)