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)

Study Overview
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Brief Summary
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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).

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

Conditions
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Male Idiopathic Infertility

Intervention / Treatment
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* Drug: FE 999049
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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) |