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.

Study Overview

• Status: Completed
• Conditions: Hypogonadism
• Intervention / Treatment: Drug: Recombinant human luteinizing hormone (r-hLH); Drug: Recombinant human follicle-stimulating hormone (r-hFSH); Drug: Human chorionic gonadotropin (hCG)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Met Both Index 1 and Index 2	The three indices were defined as; Index 1: diameter of at least one follicle is greater than 17 mm; Index 2: serum oestradiol (E2) level in blood serum above 109 picogram/ milliliter (pg/mL) on human chorionic gonadotropin (hCG) injection day; Index 3: participant refuses to take hCG injection for the concern of ovarian hyperstimulation syndrome (OHSS) or participant is pregnant. A subset of these participants met Index 3.	Day 14
Number of Participants Who Had at Least One Follicle Greater Than 17mm in Diameter		Day 14
Number of Participants With E2 Level in Blood Serum Above 109 pg/mL on the Day of hCG Injection		Day 14
Number of Participants Who Refused to Take hCG Injection	Participant refused to take hCG injection for the concern of OHSS or the participant was pregnant.	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Follicles With Diameter in the Range of 10-17 mm on the Day of hCG Injection in Treatment Cycle		Day 14
Mean Number of Follicles With the Diameter Above 17 mm on the Day of hCG Injection in Treatment Cycle		Day 14
Average Change of E2 Level in Participants Per Day up to Day 14	The average change was calculated by assessing the E2 levels on 4 timepoints until day 14 (day 1, day 5, day 10, day 14 [hCG administration day]).	up to Day 14
Number of Participants With Confirmed Pregnancies: Biochemical Pregnancies and Clinical Pregnancies	Biochemical pregnancy was defined as a pregnancy diagnosed only by the detection of hCG in serum or urine and that does not develop into a clinical pregnancy. Clinical pregnancy was defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy.	Day 14
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AE: any new untoward medical occurrence/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition.	Day 14

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Merck Pte. Ltd., Singapore
• Investigators: Study Director: Xin Li, Merck Pte. Ltd., Singapore

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: March 4, 2010
• First Submitted That Met QC Criteria: March 8, 2010
• First Posted (Estimate): March 10, 2010

Study Record Updates

• Last Update Posted (Estimate): December 27, 2013
• Last Update Submitted That Met QC Criteria: December 2, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Hypogonadism; Recombinant human follicle stimulating hormone (r-hFSH); Recombinant leutinizing hormone (r-hLH)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Hypogonadism; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Follicle Stimulating Hormone; Hormones; Chorionic Gonadotropin
• Other Study ID Numbers: IMP25345