Male Idiopathic Infertility
Conditions
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).
Interventions
DRUGFE 999049
FE 999049 is administered as single daily subcutaneous injections of 12 μg for 6 months.
DRUGPlacebo
Placebo is administered as single daily subcutaneous injection dialed to the same value (dose) as FE 999049 for 6 months.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Spontaneous Pregnancy Observed in Female Partner Within 9 Months After Randomization of Male Subject, Where Spontaneous Pregnancy is Defined as Vital Pregnancy | Up to 9 months after randomization | Vital pregnancy is documentation of at least one intrauterine gestational sac with fetal heartbeat by ultrasound. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 9 months | — |
| Changes in Semen Volume From Pre-randomisation to 9 Months After Randomization | From pre-randomisation to end of trial (9 months) | Change from baseline pre-randomisation to end of trial, which is 9 months. |
| Changes in Sperm Concentration | From pre-randomization to end of trial (9 months) | Change from baseline from pre-randomisation to end of trial, which is 9 months |
| Changes in Total Sperm Count | From pre-randomisation to end of trial (9 months) | Change from baseline from pre-randomisation to end of trial, which is 9 months |
| Changes in Total Motile Sperm Count | From pre-randomisation to end of trial (9 months) | Change from baseline from pre-randomisation to end of trial, which is 9 months |
| Changes in Sperm Morphology | From pre-randomisation to end of trial (up to 9 months) | Change from baseline from pre-randomisation to end of trial, which is 9 months |
| Changes in Semen DNA Fragmentation | From pre-randomization to end of treatment | — |
| 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 6 months after randomization | Change from baseline. |
| Changes in Luteinising Hormone (LH) | From randomisation to 3 and 6 months after randomization | From randomisation to 3 and 6 months |
| Changes in Inhibin B | From randomization to 6 months after randomization | Change from baseline. |
| Changes in Testosterone | From randomization to 6 months after randomization | Change from baseline. |
| Changes in Estradiol | From randomization to 6 months after randomization | Change from baseline. |
| Changes in Free Testosterone Concentration | From randomization to 6 months after randomization | Blood samples for assessment of sex hormone binding globulin (SHBG) concentrations will be drawn in order to calculate change from baseline in free testosterone concentrations. |
| Number of Participants With Treatment-induced Anti-FSH Antibodies, Overall as Well as With Neutralising Capacity | From randomization to 21-35 days after End-of-treatment (9 months) | Blood samples for assessment of anti-FSH antibodies will be drawn. |
| Number of Participants With Immune-related Adverse Events | From randomization to End-of-Trial (up to 9 months) | All treatment-emergent adverse events will be analyzed to identify those that potentially are immune related. |
Countries
Belgium, Denmark, Germany, Italy, Spain, Sweden, United States
Contacts
STUDY_DIRECTORGlobal Clinical Compliance
Ferring Pharmaceuticals
Participant flow
Pre-assignment details
Only male participants were enrolled in the study, and not their female partners. Enrollment information consists of only males that were exposed to FE 999049 or placebo, and does not represent dyads - please see gender baseline characteristics. Female partners were only analysed for pregnancy and not enrolled in this study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 18 - 50 years | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 0 / 1 | 0 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 |
Outcome results
None listed