Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism

Hypogonadotropic Hypogonadism Clinical Trial

Official title:

A Phase IIb Multicentre, Double-Blind, Dose-Ranging, Randomised, Placebo-Controlled Study Evaluating Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02730169
• Other study ID #: MBGS205
• Status: Completed
• Phase: Phase 2
• Start date: May 12, 2016
• Est. completion date: May 19, 2018

Study information

• Verified date: August 2022
• Source: Mereo BioPharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of BGS649 in male obese subjects with hypogonadotropic hypogonadism. All subjects will be treated for a maximum of 24 weeks. Some subjects who complete 24 weeks of treatment will be invited to participate in a 6-month blinded safety extension study (Protocol MBGS206). The study is planned to enroll 268 subjects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 271
• Est. completion date: May 19, 2018
• Est. primary completion date: February 15, 2018
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Adult male subject aged 18 to 65 years inclusive

• BMI > 30 kg/m2 and < 50 kg/m2

• Serum total testosterone concentration below the normal range

• LH levels below the upper limit of normal

• Oestradiol levels within or above the normal range of approved assay

• At least two symptoms of androgen deficiency present for at least 2 months prior to the first Screening Visit, with at least one of these being a sexual dysfunction

Exclusion Criteria:

• Evidence of clinically significant endocrinopathy at screening that may interfere with the study assessments

• Other types of hypogonadotropic hypogonadism or primary hypogonadism

• Any other pituitary or hypothalamic disease

Related Conditions & MeSH terms

• Hypogonadism
• Hypogonadotropic Hypogonadism

Intervention

Drug:
• BGS649
Capsules were taken weekly for a maximum of 24 weeks
• Placebo
Capsules were taken weekly for a maximum of 24 weeks

Locations

Country	Name	City	State
Italy	Mereo Research Site	Ancona
Italy	Mereo Research Site	Parma
Italy	Mereo Research Site	Roma
Italy	Mereo Research Site	Siena
Spain	Mereo Research Site	Coslada
Spain	Mereo Research Site	Girona
Spain	Mereo Research Site	Madrid
Spain	Mereo Research Site	Majadahonda
United Kingdom	Mereo Research Site	Barnsley
United Kingdom	Mereo Research Site	Coventry
United Kingdom	Mereo Research Site	Dundee
United Kingdom	Mereo Research Site	Edinburgh
United Kingdom	Mereo Research Site	Hull
United Kingdom	Mereo Research Site	Manchester
United Kingdom	Mereo Research Site	Newcastle
United States	Mereo Research Site	Albany	New York
United States	Mereo Research Site	Anaheim	California
United States	Mereo Research Site	Baltimore	Maryland
United States	Mereo Research Site	Birmingham	Alabama
United States	Mereo Research Site	Bradenton	Florida
United States	Mereo Research Site	Carlsbad	California
United States	Mereo Research Site	Chandler	Arizona
United States	Mereo Research Site	Charlotte	North Carolina
United States	Mereo Research Site	Dallas	Texas
United States	Mereo Research Site	DeLand	Florida
United States	Mereo Research Site	Elkridge	Maryland
United States	Mereo Research Site	Evansville	Indiana
United States	Mereo Research Site	Fort Myers	Florida
United States	Mereo Research Site	Fort Worth	Texas
United States	Mereo Research Site	Garden City	New York
United States	Mereo Research Site	Great Neck	New York
United States	Mereo Research Site	Greenbrae	California
United States	Mereo Research Site	Gurnee	Illinois
United States	Mereo Research Site	Henderson	Nevada
United States	Mereo Research Site	Hialeah	Florida
United States	Mereo Research Site	Homestead	Florida
United States	Mereo Research Site	Kenosha	Wisconsin
United States	Mereo Research Site	Las Vegas	Nevada
United States	Mereo Research Site	Lincoln	California
United States	Mereo Research Site	Los Angeles	California
United States	Mereo Research Site	Meridian	Idaho
United States	Mereo Research Site	Middleburg Heights	Ohio
United States	Mereo Research Site	Mobile	Alabama
United States	Mereo Research Site	Mount Pleasant	South Carolina
United States	Mereo Research Site	Murray	Utah
United States	Mereo Research Site	Nashville	Tennessee
United States	Mereo Research Site	New Orleans	Louisiana
United States	Mereo Research Site	New York	New York
United States	Mereo Research Site	Norfolk	Virginia
United States	Mereo Research Site	Omaha	Nebraska
United States	Mereo Research Site	Pearland	Texas
United States	Mereo Research Site	Phoenix	Arizona
United States	Mereo Research Site	Raleigh	North Carolina
United States	Mereo Research Site	Rochester	New York
United States	Mereo Research Site	Saint Louis	Missouri
United States	Mereo Research Site	Saint Petersburg	Florida
United States	Mereo Research Site	San Antonio	Texas
United States	Mereo Research Site	San Diego	California
United States	Mereo Research Site	Scottsdale	Arizona
United States	Mereo Research Site	Smyrna	Tennessee
United States	Mereo Research Site	Spring Hill	Tennessee
United States	Mereo Research Site	West Jordan	Utah
United States	Mereo Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Mereo BioPharma

Countries where clinical trial is conducted

United States,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mean (SD) Change From Baseline in Prostate Specific Antigen (PSA) to Week 24.	PSA was measured alongside other clinical chemistry parameters at screening, baseline, Visits 1 through 8 and at follow-up.	Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks
Other	Mean (SD) Change From Baseline in Haematocrit to Week 24.	Haematocrit was measured alongside other haematology parameters at screening, baseline, Visits 1 through 8 and at follow-up.	Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks
Other	Mean (SD) Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan T-score by Location at Week 24.	Summary of DEXA Scan T-score at Visit 8 (Week 24) in the hip, femoral neck, and lumber spine. DEXA T-score was calculated based on actual measured bone density value and compared to a standard reference range for healthy young adult men.; A bone density scan compares bone density with the bone density expected for a young healthy adult or a healthy adult of the same age, gender and ethnicity. The difference is calculated as a standard deviation (SD) score. The measures between the bone density and the expected value of a young healthy adult is known as the T score.; The World Health Organization (WHO) classifies T scores as follows: above -1 SD is normal; between -1 and -2.5 SD is defined as mildly reduced bone mineral density (BMD) compared with peak bone mass (PBM); at or below -2.5 SD is defined as osteoporosis	Screening to Week 24
Other	Mean (SD) Change From Baseline in DEXA Scan Density by Location at Week 24	Summary of DEXA scan density at Visit 8 (Week 24) in the hip, femoral neck, and lumber spine. Bone density was evaluated with standard procedure for Hologic and General Electric Lunar scanners.	Screening to Week 24
Other	Mean (SD) Change From Baseline in Bone Turnover Markers by Parameter at Week 24.	Descriptive statistics were presented for the following bone turnover marker parameters: type I collagen C-telopeptides, procollagen 1 N-terminal propeptide, osteocalcin, and bone specific alkaline phosphatase.	Screening to Week 24
Other	Change From Baseline in Bone Specific Alkaline Phosphatase at Week 24.	Change from baseline in bone specific alkaline phosphatase at week 24 measured in U/L	24 weeks
Primary	Percentage of Patients With Normalised Testosterone After 24 Weeks of Study Treatment	Percentage of patients with normalised testosterone i.e. testosterone in the range 300-1000ng/dL after 24 weeks of study treatment. The primary objective was considered met, if greater than or equal to 75% of the participants in any arm normalised.	24 weeks of treatment
Secondary	The Proportion of Subjects That Have Normalization of Total Testosterone Serum Concentrations From Baseline to Week 24	Normalised total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range.	Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks
Secondary	Proportion of Subjects That Overshoot Testosterone (Total Testosterone Above 1000 ng/dL [35 Nmol/L]) From Baseline to Week 24	Testosterone overshoot was defined as total testosterone above 1000 ng/dL (35 nmol/L). Samples were collected in the morning before 11 am pre dose.	Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks
Secondary	Normalization of Total Testosterone Serum Concentrations in = 90% Subjects After 24 Weeks of Treatment.	Normalized total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range. This secondary outcome measure was considered to have been met for a dose if = 90% of subjects in the intent-to-treat (ITT) population had normalisation of total testosterone levels at Week 24.	24 weeks of treatment
Secondary	Mean (SD) Change From Baseline in Luteinizing Hormone (LH) to Week 24.	LH was measured at screening, baseline. The Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.	Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks
Secondary	Mean (SD) Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 24.	FSH was measured at baseline, Visit 1 through 8 and follow-up. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.	Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks
Secondary	Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Plasma PK Concentration Values to 24 Weeks.	Plasma PK sampling for BGS649 was performed at Weeks 12 and 24. BGS649 PK plasma concentrations were summarised for the PK population by descriptive statistics.	Week 12 (pre-dose and 1 hour post-dose), week 24 and week 24/End of treatment
Secondary	Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Semen PK Concentration Values at 24 Weeks.	Semen PK sampling for BGS649 was performed at Visit 8 (End of Treatment). BGS649 PK semen concentrations were summarised for the PK population by descriptive statistics.	Week 24 and week 24/End of treatment