A Study Using Recombinant Human Luteinizing Hormone (r-hLH, Luveris®) in the Treatment of Chinese Women With Hypogonadotropic Hypogonadism

Clinical Trial on Application of Injectable Recombinant Human Luteinizing Hormone (Luveris®) in the Treatment of Chinese Female Patients With Hypogonadotropic Hypogonadism: A Multi-center, Open, Prospective Drug Clinical Trial for Registration

This was a prospective, open, non-comparative study to evaluate the safety and efficacy of recombinant human luteinizing hormone (rhLH, Luveris) administered subcutaneously (s.c.) in follicular development during ovulation induction in 31 Chinese female subjects with hypogonadotropic hypogonadism.

The objective of this prospective, open, non-comparative study was to assess the safety and efficacy of rhLH (Luveris) administered subcutaneously in follicular development during ovulation induction in Chinese female subjects with hypogonadotropic hypogonadism. The study was organized on an outpatient basis involving a single cycle of treatment. Prior to entry into the study, the diagnosis of hypogonadotropic hypogonadism was confirmed by history, by the presence or absence of specific clinical features and by measuring serum gonadotropin levels. Once a subject has signed the informed consent form and after satisfying all eligibility criteria, the subject received a combination of daily injection of recombinant human follicle-stimulating hormone (rhFSH) 150 international units (IU) plus rhLH 75 IU. After adequate follicular response, ovulation induction was triggered by an injection of 10,000 IU human chorionic gonadotropin (hCG). Luteal phase function was assessed by serum progesterone level determination.

Inclusion Criteria:

• Be premenopausal, between 18 and 39 years of age
• Have a clinical history of hypogonadotropic hypogonadism, and laboratory test result comply with diagnosis of hypogonadotropic hypogonadism during screening procedure
• Have discontinued gonadotropins, gonadotropin-releasing hormone (GnRH) (gonadotropin naïve), or estrogen progesterone replacement therapy at least one month before the screening procedure
• Have a negative progestin challenge test performed during screening
• Have the following hormonal values in a centrally analyzed fasting blood sample, drawn within 6 months before initiation of treatment:
• Follicular stimulating hormone (FSH): < 5 international units/liter (IU/L)
• Luteinizing hormone (LH): < 1.2 IU/L
• Oestradiol (E2): < 60 picogram/milliliter (pg/mL) (<220 picomolar/liter [pmol/L])
• Prolactin (PRL): < 44.3 nanogram/milliliter (ng/mL) (< 1040 milli-international units/liter [mIU/L])
• Thyrotrophin-stimulating hormone (TSH): < 6.5 micro-international units (uIU/mL)
• Free Thyroxine (T4): 0.8-1.8 nanogram/deciliter (ng/dL) (11-24 pmol/L)
• Triiodothyronine (T3): < 1.0 ng/mL (< 3.5 nanomolar/liter [nmol/L])
• Have an endovaginal pelvic ultrasound scan showing (i) no ovarian tumor and cyst < 2 centimeters (cm); (ii) no clinically significant uterine abnormality, and (iii) < 13 mm small follicles (mean diameter < 10 mm) on the largest section through each ovary
• Have a normal cervical pap smear within 6 months of the initial visit
• Have a body mass index (BMI) between 18.4 and 31.4 kilogram/meter square (kg/m^2)
• 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

Exclusion Criteria:

• Ongoing pregnancy
• Any chronic systemic disease
• Hypersensitive to study drug and control drug
• History of severe ovarian hyperstimulation syndrome
• Abnormal gynecological bleeding of undetermined origin
• Previous or current hormone dependent tumor
• Known active substance abuse or eating disorder
• Known central nervous system (CNS) lesions: In cases where hypogonadotropic hypogonadism (HH) is secondary to a CNS lesion or its treatment, the subject will not be eligible without consulting Serono's Medical Director
• Exercise program exceeding 10 hours per week
• Currently undergoing treatment with psychotropic medication or with any other medication known to interfere with normal reproductive function (for example, neuroleptics, dopamine antagonists)
• There is any abnormality, decided by investigators, which might produce effect on the absorption, distribution and excretion of investigational drug