Clinical trial NCT00553514: AS900672-Enriched in Ovulation Induction
Official title: A Phase II, Multicentre, Randomised, Assessor-blinded, Active-comparator, Parallel-group Dose Finding Trial to Evaluate AS900672-enriched Versus Follitropin Alfa (GONAL-f®) in Oligo-anovulatory Infertile Women Undergoing Ovulation Induction (OI)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ovulation Induction
Keywords: Infertility
Oligo-anovulation
GONAL-f®
AS900672-Enriched
hyperglycosylated recombinant human follicle stimulating hormone (r-hFSH)
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2007-11-04
Enrollment: 71
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 36
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2, interventional, multi-center, randomized, assessor-blind, active-comparator, dose-finding study to evaluate a new investigational long-acting follicle stimulating hormone (FSH) in oligo-anovulatory women undergoing ovulation induction (OI). This study will compare 4 doses of the investigational drug versus a currently marketed drug follitropin alfa (Gonal-f ®) prefilled pen with regards to ovulation rate.

Detailed description: The study was terminated after Merck Serono had taken the decision not to pursue the development of AS900672-enriched in ovulation induction (OI). This decision was not related to any safety or efficacy concerns over the use of AS900672-Enriched in OI.

Eligibility criteria: Inclusion Criteria:

* Oligo-anovulation defined by a menstrual period of 35 days to 6 months
* Spontaneous menses or a positive response to progestin within the prior 6 months or response to clomiphene citrate evidenced by ovulation within the prior 6 months
* Age between 18 and 36 years, inclusive, at time of informed consent signature
* Body mass index (BMI) 18 to 30 kilogram per square meter (kg/m\^2), inclusive
* No clinically significant abnormalities in serum thyroid stimulating hormone (TSH), dehydroepiandrosterone (DHEA-S), prolactin, and FSH levels in the early follicular phase. Subjects low TSH level who receive replacement therapy could be enrolled at the discretion of the investigator if local laboratory results (thyroxine \[T4\]) demonstrated satisfactory thyroid function. Subjects receiving stable dose of dopamine agonists could be enrolled at the discretion of the investigator if local laboratory results demonstrated adequate control of prolactin levels
* No clinically significant abnormalities in fasting glucose and fasting insulin levels
* Normal uterine cavity and presence of at least one ovary with ipsilateral patent fallopian tube, as determined by means of hysterosalpingography, laparoscopy, hysteroscopy or combination of these procedures within the prior 3 years
* Papanicolaou (PAP) smear test without clinically significant abnormalities within 6 months prior to the first screening procedure. If PAP smear is not done, it must be performed as part of screening procedures
* Negative pregnancy test prior to randomization
* Male partner with semen analysis demonstrating adequacy for insemination via intercourse and/or intrauterine insemination (IUI) within 6 months prior to the first screening procedure. If semen analysis is not done, it must be performed as part of screening procedures
* Willing and able to comply with all protocol procedures, including pregnancy and neonatal follow-up
* Voluntary provision of written informed consent, prior to any trial-related procedure that is not part of normal medical care, with the understanding that the subject could withdraw consent at any time without prejudice to her future medical care, including willingness to provide follow-up information on babies born as part of this trial

Exclusion Criteria:

* History of \>=2 consecutive gonadotrophin stimulation cycles that did not lead to ovulation
* History of clomiphene citrate stimulation cycles of which none lead to ovulation
* Prior excessive response to gonadotrophin stimulation, defined as the development of at least 4 mature follicles (greater than \[\>\]17 mm) or cancellation of the OI cycle due to excessive follicular response after treatment with FSH at a dose of less than 75 IU/day
* Previous severe ovarian hyperstimulation syndrome (OHSS)
* Administration of any gonadotrophin, clomiphene citrate, gonadotrophin releasing hormone (GnRH) analogue, tamoxifen or aromatase inhibitors within the prior 30 days
* Laparoscopic ovarian drilling and/or ovarian cauterization within the prior 6 months
* Any contraindication to pregnancy and/or to carrying pregnancy to term
* A clinical pregnancy that ended in a miscarriage within the prior 3 months
* History of \>=3 consecutive miscarriages, due to any cause
* Abnormal gynecological bleeding of undetermined origin
* Clinically significant abnormal findings of the uterine cavity evident on a transvaginal pelvic ultrasound performed during screening
* Presence of endometriosis, Grade III - IV or requiring treatment
* Ovarian cyst with a mean diameter of \>25 mm on the day of randomization
* History or suspicion of ovarian, uterine or mammary cancer
* Adrenal congenital hyperplasia, partial or complete enzymatic block
* Use of metformin or other insulin sensitizing agents related to infertility within the prior 2 months
* Known allergy or hypersensitivity to human gonadotrophin preparations or to compounds that are structurally similar to any of the other medications administered during the trial
* Any contra-indication to gonadotrophin therapy
* Known or suspected infection with human immunodeficiency virus (HIV), Hepatitis B or C in the trial subject or her male partner
* Any active substance abuse or history of drug, medication or alcohol abuse within 5 years
* Smoker consuming more than 5 cigarettes per day
* Serum testosterone (central laboratory) that is suggestive of ovarian tumor
* Previously randomized in this trial or participation in another investigational drug clinical trial within the prior 3 months
* Any medical condition, which in the judgment of the investigator may interfere with the absorption, distribution, metabolism or excretion of r-hFSH
* Clinically significant concurrent disease (including diabetes mellitus and autoimmune diseases) that would compromise subject safety or interfere with the study assessments or clinically significant abnormal laboratory finding

Primary outcomes:
measure: Percentage of Participants With Ovulation
timeFrame: Mid-luteal phase progesterone assessed 5-10 days or clinical pregnancy 35-42 days after recombinant human chorionic gonadotropin (r-hCG) administration day (end of stimulation cycle [approximately 14 days])
Secondary outcomes:
measure: Percentage of Participants With Clinical Pregnancy
timeFrame: Day 35-42 post r-hCG administration day (end of stimulation cycle [approximately 14 days])
measure: Duration of Ovarian Stimulation
timeFrame: Stimulation Day 1 (S1) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
measure: Duration of Supplemental Follitropin Alfa Treatment
timeFrame: Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
measure: Cumulative Dose of Supplemental Follitropin Alfa Administered
timeFrame: Stimulation Day 7 (S7) up to r-hCG administration day (end of stimulation cycle [approximately 14 days])
measure: Number of Follicles With Mean Diameter Less Than (<) 11 Millimeter (mm) and Greater Than or Equal to (>=) 11 mm
timeFrame: Stimulation Day 5 (S5), S7 and r-hCG administration day (end of stimulation cycle [approximately 14 days])
Other outcomes:
Locations:
city: Geneva
country: Switzerland
facility: Merck Serono S.A.
Study officials:
affiliation: IVI Valencia
name: Antonio Pellicer, Professor Dr
role: PRINCIPAL_INVESTIGATOR
References: