A Trial to Compare Efficacy and Safety of Follitropin Delta Versus Placebo (Inactive Treatment) in the Treatment of Men With Idiopathic Infertility (Unexplained Reduction of Semen Quality) (ADAM)

A Randomised, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of FE 999049 for Treatment of Men With Idiopathic Infertility

The primary purpose of this trial is to investigate whether men with idiopathic infertility (unexplained reduction of semen quality), after being treated with a daily dose of 12 µg recombinant follicle stimulating hormone (rFSH) for 6 months, can improve the chance of spontaneous pregnancy observed in their female partners in comparison to placebo (inactive treatment). For more information, please visit the trial's website www.adamclinicaltrial.com (only applicable in the US).

Study Overview

• Status: Recruiting
• Conditions: Male Idiopathic Infertility
• Intervention / Treatment: Drug: FE 999049; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Global Clinical Compliance; Phone Number: +1 833-548-1402 (US/Canada); Email: DK0-Disclosure@ferring.com
• Study Contact Backup: Name: Global Clinical Compliance; Phone Number: +1 862-286-5200 (outside US); Email: DK0-Disclosure@ferring.com

Study Locations

• Belgium
  • Brussel, Belgium
    • Recruiting
    • Ferring Investigational Site
  • Brussels, Belgium
    • Recruiting
    • Ferring Investigational Site
• Denmark
  • Copenhagen, Denmark
    • Recruiting
    • Ferring Investigational Site
• Germany
  • Halle, Germany
    • Recruiting
    • Ferring Investigational Site
  • Muenster, Germany
    • Recruiting
    • Ferring Investigational Site
• Italy
  • Modena, Italy
    • Recruiting
    • Ferring Investigational Site
  • Rome, Italy
    • Recruiting
    • Ferring Investigational Site
• Spain
  • Valencia, Spain
    • Recruiting
    • Ferring Investigational Site
• Sweden
  • Malmö, Sweden
    • Recruiting
    • Ferring Investigational Site
  • Stockholm, Sweden
    • Recruiting
    • Ferring Investigational Site
• United States
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Recruiting
      • Ferring Investigational Site
  • California
    • San Jose, California, United States, 95124
      • Recruiting
      • Ferring Investigational Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Recruiting
      • Ferring Investigational Site
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • Ferring Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Ferring Investigational Site
    • Chicago, Illinois, United States, 60611
      • Withdrawn
      • Ferring Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • Ferring Investigational Site
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Ferring Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Recruiting
      • Ferring Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • Ferring Investigational Site
  • Texas
    • Bedford, Texas, United States, 76022
      • Recruiting
      • Ferring Investigational Site
    • Webster, Texas, United States, 77598
      • Recruiting
      • Ferring Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • Recruiting
      • Ferring Investigational Site
  • Washington
    • Seattle, Washington, United States, 98195
      • Recruiting
      • Ferring Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• History of infertility for 12-60 months with current partner at randomization.
• Men between the ages of 18 and 50 years.
• Total sperm count 5-39 million at screening; confirmed by two consecutive samples taken ≥2 weeks apart before randomization.
• Total motile sperm count of 5-16 million at screening; confirmed by two consecutive samples taken ≥2 weeks apart before randomization.
• Semen volume ≥1.4 mL at screening; confirmed by two consecutive samples taken ≥2 weeks apart before randomization.
• Serum follicle-stimulating hormone (FSH) levels of 1.5-8.0 IU/L (measured at central laboratory) at screening.
• Serum luteinising hormone (LH) levels of 1.2-7.5 IU/L (measured at central laboratory) at screening.
• Serum total testosterone levels of ≥300 ng/dL (equals ≥10.4 nmol/L; measured at central laboratory) at screening.
• Agree to have regular intercourse with current female partner with the intent of spontaneous conception within 9 months from randomization.
• Agree to provide information on female partner's positive urine pregnancy test(s) and documentation of ultrasound(s), delivery, and neonatal/infant health.

Current partner fulfilling the criteria below:

• Pre-menopausal woman between the ages of 18 and 35 years.
• Regular menstrual cycles of 21-35 days.
• No history or current condition of pelvic inflammatory disease, endometriosis stage II-IV by definite or empirical diagnosis, or tubal ligation.
• Agree not to obtain infertility treatment outside of this trial for 9 months from randomization of male subject.

Exclusion Criteria:

• Previous FSH treatment not leading to conception.
• Past or current use of finasteride within 3 months prior to screening.
• Any history of anatomical disorder of the pituitary gland or testes.
• Any structural abnormalities of the vas deferens (unilateral or bilateral) at screening.
• Any known, clinically significant, systemic disease in addition to the trial indication that might negatively impact fertility.
• Known history or presence of clinical varicocele (subclinical and Grade 1 varicocele are acceptable).
• Known history of cryptorchidism, testicular torsion, or orchitis.
• Known abnormal karyotype (including Y-chromosome microdeletion).
• Current or past treatment of urogenital (kidney, bladder, testicular, or prostate) cancer as well as history of chemo- or radiotherapy that can have impact on testes.
• Any known uncontrolled non-gonadal endocrinopathies (thyroid, adrenal, pituitary disorders).
• Administration of hormonal preparations, agents known to impair testicular function or affect sex hormone secretion, and known or suspected teratogens within 3 months prior to screening. Administration of anabolic steroids within 12 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo is administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049 for 6 months.
Experimental: FE 999049 (Follitropin Delta)	Drug: FE 999049; FE 999049 is administered as single daily subcutaneous injections of 12 μg for 6 months.; Other Names: REKOVELLE; Follitropin Delta

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous pregnancy observed in female partner within 9 months after randomization of male subject, where spontaneous pregnancy is defined as vital pregnancy	Vital pregnancy is documentation of at least one intrauterine gestational sac with fetal heartbeat by ultrasound.	Up to 9 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Beta-Human Chorionic Gonadotropins (βhCG) (positive urine βhCG test) observed in female partner		Up to 9 months (End-of-Trial)
Time from randomization to spontaneous pregnancy observed in female partner in calendar time and number of menstrual cycles		Up to 9 months (End-of-Trial)
Changes in semen volume from pre-randomization to 3, 6, and 9 months after randomization		From pre-randomization to 3, 6 and 9 months after randomization
Changes in sperm concentration from pre-randomization to 3, 6, and 9 months after randomization		From pre-randomization to 3, 6 and 9 months after randomization
Changes in total sperm count from pre-randomization to 3, 6, and 9 months after randomization		From pre-randomization to 3, 6 and 9 months after randomization
Changes in total motile sperm count from pre-randomization to 3, 6, and 9 months after randomization		From pre-randomization to 3, 6 and 9 months after randomization
Changes in sperm morphology from pre-randomization to 3, 6, and 9 months after randomization		From pre-randomization to 3, 6 and 9 months after randomization
Changes in semen DNA fragmentation from pre-randomization to 3, 6, and 9 months after randomization		From pre-randomization to 3, 6 and 9 months after randomization
Treatment responders defined by either spontaneous pregnancy observed in female partner, or increase of total sperm count or total motile sperm count to 50% over average baseline at 6 and/or 9 months		Baseline to 6 and 9 months
Changes in follicle stimulating hormone (FSH) from randomization to 3 and 6 months after randomization		From randomization to 3 and 6 months after randomization
Changes in luteinising hormone (LH) from randomization to 3 and 6 months after randomization		From randomization to 3 and 6 months after randomization
Changes in inhibin B from randomization to 3 and 6 months after randomization		From randomization to 3 and 6 months after randomization
Changes in testosterone from randomization to 3 and 6 months after randomization		From randomization to 3 and 6 months after randomization
Changes in estradiol from randomization to 3 and 6 months after randomization		From randomization to 3 and 6 months after randomization
Changes in free testosterone concentration from randomization to 3 and 6 months after randomization	Blood samples for assessment of sex hormone binding globulin (SHBG) concentrations will be drawn in order to calculate free testosterone concentrations.	From randomization to 3 and 6 months after randomization
Treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity	Blood samples for assessment of anti-FSH antibodies will be drawn.	From randomization to 21-35 days after End-of-treatment
Immune-related adverse events	All treatment-emergent adverse events will be analyzed to identify those that potentially are immune related.	From randomization to End-of-Trial (up to 9 months)

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2022
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026

Study Registration Dates

• First Submitted: May 30, 2022
• First Submitted That Met QC Criteria: May 30, 2022
• First Posted (Actual): June 3, 2022

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Follicle Stimulating Hormone
• Other Study ID Numbers: 000400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No