Clinical trial NCT01735422: A Study to Evaluate Safety and Efficacy of Recombinant Human Luteinizing Hormone (r-hLH) Compared With Urinary Human Chorionic Gonadotrophin (u-hCG) to Trigger Ovulation in Infertile Women
Official title: A Phase II, Single Center, Open, Randomized, Parallel Group, Dose Finding Study to Assess the Safety and Efficacy of Recombinant Human Luteinizing Hormone (r-hLH), Compared With Urinary Human Chorionic Gonadotrophin (u-hCG), in Inducing Ovulation in Infertile Women Undergoing Stimulation of Follicular Development With Recombinant Human Follicle Stimulating Hormone (Gonal F®).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infertility
Keywords: Infertility
Ovulation induction
Recombinant human Luteinizing Hormone (r-hLH)
Urinary human Chorionic Gonadotrophin (u-hCG)
Recombinant human Follicle Stimulating Hormone (Gonal-f®)
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2012-11-28
Enrollment: 67
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single center, open-label, randomized, parallel group, dose finding study to evaluate safety and efficacy of recombinant human luteinizing hormone (r-hLH, LHadi®), compared with urinary human chorionic gonadotrophin (u-hCG, Profasi®), both given subcutaneously, in inducing ovulation in infertile women undergoing stimulation of follicular growth with recombinant human follicle stimulating hormone (r-hFSH, Gonal-F®).


Eligibility criteria: Inclusion Criteria:

* Infertile woman wishing to conceive and justifying ovarian stimulation treatment with gonadotrophins for in vivo conception
* Aged 20-40 years (inclusive)
* Male partner with acceptable semen analysis for intra-uterine insemination, according to center's standard practice
* Have the following hormone serum levels measured locally during early (Day 2-4) follicular phase (if menstruating) or at anytime (if not menstruating):

  * Follicle stimulating hormone (FSH) less than 12 international unit per liter (IU/L)
  * Prolactin (PRL) less than 800 milli international unit per liter (mIU/l)
  * Lutenizing hormone (LH), P4, Testosterone (T) and Dehydroepiandrosterone sulphate (DHEA-S) for documentation purposes
* At least one patent tube, as assessed with hysterosalpingography (HSG), ultrasound (U/S) or laparoscopy performed within 3 years prior to beginning r-hFSH treatment
* Uterine cavity without abnormalities which, in the Investigator's opinion, could impair embryo implantation or pregnancy evolution as assessed with HSG, hysteroscopy (HSC) or U/S performed within 3 years prior to beginning r-hFSH treatment
* Body mass index (BMI) greater than or equal to 18 and less than or equal to 35 kilogram per square meter (kg/m\^2)
* Negative serum or urinary pregnancy test prior to beginning r-hFSH treatment
* Be willing and able to comply with the protocol for the duration of the study
* Have given written informed consent, prior to any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care

Exclusion Criteria:

* Any contraindication to being pregnant and/or carrying a pregnancy to term
* Clinically significant systemic disease (screening for Human Immunodeficiency Virus (HIV) and Hepatitis B and C surface antigens had to be performed to confirm eligibility, unless data obtained within one year prior to beginning r-hFSH treatment was available)
* Any medical condition which in the judgment of the Investigator's and sponsor may have interfered with the absorption, distribution, metabolism or excretion of the study drug
* Persistent ovarian cyst with a mean diameter larger than 20 mm or ovarian endometrioma, as assessed with U/S performed prior to beginning r-hFSH treatment
* Severe endometriosis (American Fertility Society Classification Stage III or IV)
* World health organization (WHO) Group I anovulation
* Pelvic inflammatory disease within 1 year prior to beginning r-hFSH treatment
* Treatment with clomiphene citrate or gonadotrophins within 1 month prior to beginning r-hFSH treatment
* Abnormal undiagnosed gynecological bleeding
* Known allergy or hypersensitivity to human gonadotrophins preparations
* Known or current substance abuse
* Previous participation in this study or simultaneous participation in another clinical trial

Primary outcomes:
measure: Ovulation rate
timeFrame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Ratio of ruptured follicles per follicle with diameter greater than or equal to (>=) 15 millimeter (mm)
timeFrame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of follicles with diameter greater than or equal to (>=) 11 millimeter (mm)
timeFrame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Ratio of ruptured follicles per follicle with diameter greater than or equal to (>=) 11 millimeter (mm)
timeFrame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Secondary outcomes:
measure: Percentage of participants with mono-follicular ovulation
timeFrame: Day 4 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of participants with biochemical pregnancy
timeFrame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum estradiol (E2) levels
timeFrame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum androstenedione levels
timeFrame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum total renin levels
timeFrame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum vascular endothelial growth factor (VEGF) levels
timeFrame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Endometrial thickness
timeFrame: Day 0, 1, 2, 3, 4 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Number of participants with clinical pregnancy
timeFrame: Day 25-30 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
measure: Serum progesterone (P4) levels
timeFrame: Day 1, 2 and 6-9 post r-hLH/u-hCG day (end of stimulation cycle [approximately 28 days])
Other outcomes:
Locations:
city: Saskatoon
country: Canada
facility: Royal University Hospital
state: Saskatchewan
Study officials:
affiliation: Merck Serono International SA
name: Medical Responsible
role: STUDY_DIRECTOR
References: