Clinical trial NCT05403476: 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)
Official title: A Randomised, Double-blind, Placebo-controlled Trial to Assess the Efficacy and Safety of FE 999049 for Treatment of Men With Idiopathic Infertility
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Male Idiopathic Infertility
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-06-03
Enrollment: 4
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: Inclusion Criteria:

* History of infertility with current partner at randomisation must be 12-60 months if current partner is aged \<35 years or 6-60 months if current partner is aged 35-38 years.
* 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 sperm motility of ≥10% at screening; confirmed by two samples taken ≥2 weeks apart before randomisation. If a semen sample has been taken within 3 months prior to screening and been analysed at an andrology laboratory, it can be included as the first of the two semen samples at screening.
* 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 2-12.0 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 38 years (both inclusive) at the time of randomisation of male participant.
* 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 6 months from randomization of male subject.

Exclusion Criteria:

* Previous FSH treatment for ≥4 months 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.

Primary outcomes:
measure: Spontaneous pregnancy observed in female partner within 9 months after randomization of male subject, where spontaneous pregnancy is defined as vital pregnancy
timeFrame: Up to 9 months after randomization
Secondary outcomes:
measure: Positive Beta-Human Chorionic Gonadotropins (βhCG) (positive urine βhCG test) observed in female partner
timeFrame: Up to 9 months (End-of-Trial)
measure: Time from randomization to spontaneous pregnancy observed in female partner in calendar time and number of menstrual cycles
timeFrame: Up to 9 months (End-of-Trial)
measure: Changes in semen volume from pre-randomization to 3, 6, and 9 months after randomization
timeFrame: From pre-randomization to 3, 6 and 9 months after randomization
measure: Changes in sperm concentration from pre-randomization to 3, 6, and 9 months after randomization
timeFrame: From pre-randomization to 3, 6 and 9 months after randomization
measure: Changes in total sperm count from pre-randomization to 3, 6, and 9 months after randomization
timeFrame: From pre-randomization to 3, 6 and 9 months after randomization
measure: Changes in total motile sperm count from pre-randomization to 3, 6, and 9 months after randomization
timeFrame: From pre-randomization to 3, 6 and 9 months after randomization
measure: Changes in sperm morphology from pre-randomization to 3, 6, and 9 months after randomization
timeFrame: From pre-randomization to 3, 6 and 9 months after randomization
measure: Changes in semen DNA fragmentation from pre-randomization to 3, 6, and 9 months after randomization
timeFrame: From pre-randomization to 3, 6 and 9 months after randomization
measure: 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
timeFrame: Baseline to 6 and 9 months
measure: Changes in follicle stimulating hormone (FSH) from randomization to 3 and 6 months after randomization
timeFrame: From randomization to 3 and 6 months after randomization
measure: Changes in luteinising hormone (LH) from randomization to 3 and 6 months after randomization
timeFrame: From randomization to 3 and 6 months after randomization
measure: Changes in inhibin B from randomization to 3 and 6 months after randomization
timeFrame: From randomization to 3 and 6 months after randomization
measure: Changes in testosterone from randomization to 3 and 6 months after randomization
timeFrame: From randomization to 3 and 6 months after randomization
measure: Changes in estradiol from randomization to 3 and 6 months after randomization
timeFrame: From randomization to 3 and 6 months after randomization
measure: Changes in free testosterone concentration from randomization to 3 and 6 months after randomization
timeFrame: From randomization to 3 and 6 months after randomization
measure: Treatment-induced anti-FSH antibodies, overall as well as with neutralising capacity
timeFrame: From randomization to 21-35 days after End-of-treatment
measure: Immune-related adverse events
timeFrame: From randomization to End-of-Trial (up to 9 months)
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Ferring Investigational Site
state: Arizona
city: San Jose
country: United States
facility: Ferring Investigational Site
state: California
city: Centennial
country: United States
facility: Ferring Investigational Site
state: Colorado
city: Newark
country: United States
facility: Ferring Investigational Site
state: Delaware
city: Chicago
country: United States
facility: Ferring Investigational Site
state: Illinois
city: Kansas City
country: United States
facility: Ferring Investigational Site
state: Kansas
city: New York
country: United States
facility: Ferring Investigational Site
state: New York
city: Raleigh
country: United States
facility: Ferring Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: Ferring Investigational Site
state: Oklahoma
city: Bedford
country: United States
facility: Ferring Investigational Site
state: Texas
city: Webster
country: United States
facility: Ferring investigational site
state: Texas
city: Salt Lake City
country: United States
facility: Ferring Investigational Site
state: Utah
city: Seattle
country: United States
facility: Ferring Investigational Site
state: Washington
city: Brussels
country: Belgium
facility: Ferring Investigational Site
city: Brussel
country: Belgium
facility: Ferring Investigational Site
city: Copenhagen
country: Denmark
facility: Ferring Investigational Site
city: Halle
country: Germany
facility: Ferring Investigational Site
city: Muenster
country: Germany
facility: Ferring Investigational Site
city: Modena
country: Italy
facility: Ferring Investigational Site
city: Rome
country: Italy
facility: Ferring Investigational Site
city: Valencia
country: Spain
facility: Ferring Investigational Site
city: Malmö
country: Sweden
facility: Ferring Investigational Site
city: Stockholm
country: Sweden
facility: Ferring Investigational Site
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: