Functional Hypothalamic Amenorrhea (FHA)
Conditions
Keywords
Secondary amenorrhea, Hypothalamic-Pituitary-Ovarian (HPO) axis, Group I ovulation disorder, Hypogonadotropic hypogonadal anovulation
Brief summary
This study is researching an experimental drug called mibavademab (also called "study drug"). The study is focused on patients with a condition called Functional Hypothalamic Amenorrhea (FHA). FHA is a condition where a woman stops menstruating because the brain is not sending the correct hormonal signals to the ovaries, which then are not able to cycle and ovulate properly. The aim of the study is to see how well the study drug helps the body make the hormones necessary for ovulation and reproduction, and to assess its safety. The study is looking at several other research questions, including: * Whether the drug helps bone health * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
Interventions
DRUGMibavademab
Administered per the protocol
OTHERPlacebo
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Diagnosis of FHA after exclusion of anatomic or organic causes of amenorrhea 2. Has had no menstrual bleeding episode within 3 months (or longer) prior to day 1, as described in the protocol 3. Has a Body Mass Index (BMI) ≥18.5 and \<25 kg/m\^2 at screening, or BMI ≥25 to \<30 kg/m\^2 at screening AND percentage of body fat \<20% from rigorous exercise as determined by the investigator through Standard of Care (SoC) methods (eg, skinfold thickness, DXA, bioimpedance) within 6 months of screening, as described in the protocol Key
Exclusion criteria
1. Has presence of primary amenorrhea (failure to reach menarche, first menstrual cycle) 2. Has blood estradiol ≥50 pg/mL or blood progesterone ≥1 ng/mL at screening 3. Has uterine (eg, absence of uterus, prior endometrial ablation, endometriosis, outflow tract disorders) or ovarian (eg, absence of an ovary, presence of polycystic ovaries) conditions that impact assessment of menses or of the HPO axis 4. Has conditions other than FHA that may cause amenorrhea or menstrual cycle disturbances (eg, polycystic ovarian syndrome, hyperprolactinemia, primary ovarian insufficiency, untreated primary hypothyroidism, primary hyperthyroidism) 5. Polycystic ovarian morphology with an ovarian volume \>10 cc on TransVaginal UltraSound (TVUS) \[or TransAbdominal Pelvic Ultrasound (TAPU) if applicable\] at baseline 6. Presence of follicle ≥17 mm, evidence of ruptured follicle, and/or evidence of corpus luteum on TVUS (or TAPU if applicable) at baseline NOTE: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from the highest serum estradiol observed during a 28-day period | Baseline to month 6 |
Secondary
| Measure | Time frame |
|---|---|
| Change from the mean serum estradiol observed during a 28-day period | Baseline to month 6 |
| Occurrence of menses followed by mid-cycle serum estradiol ≥200 pg/ml and mid-luteal serum progesterone ≥7.9 ng/ml | At month 6 |
| Change in the highest serum estradiol | Baseline through 6 months |
| Occurrence of serum estradiol ≥200 pg/ml | Through 6 months |
| Number of ovulatory menstrual cycles | Through 6 months |
| Number of menses with mid-luteal serum progesterone ≥7.9 ng/ml and midluteal estradiol ≥100 pg/ml | Through 6 months |
| Number of menstrual cycles | Through 6 months |
| Percent change in Bone Mineral Density (BMD) at the lumbar spine, as measured by Dual X-ray Absorptiometry (DXA) | Baseline to 6 months |
| Absolute change in BMD at the lumbar spine, as measured by DXA | Baseline to 6 months |
| Percent change in Bone Mineral Content (BMC) at the lumbar spine, as measured by DXA | Baseline to 6 months |
| Absolute change in BMC at the lumbar spine, as measured by DXA | Baseline to 6 months |
| Percent change in BMD at the lumbar spine, as measured by DXA in participants with baseline lumbar spine BMD Z-score <-1 | Baseline to 6 months |
| Absolute change in BMD at the lumbar spine, as measured by DXA, in participants with baseline lumbar spine BMD Z-score <-1 | Baseline to 6 months |
| Percent change in BMC at the lumbar spine, as measured by DXA, in participants with baseline lumbar spine BMD Z-score <-1 | Baseline to 6 months |
| Absolute change in BMC at the lumbar spine, as measured by DXA, in participants with baseline lumbar spine BMD Z-score <-1 | Baseline to 6 months |
| Occurrence of Treatment Emergent of Adverse Events (TEAEs) | Up to day 280 |
| Severity of TEAEs | Up to day 280 |
| Concentrations of total mibavademab in serum | Up to day 280 |
| Occurrence of Anti-Drug Antibodies (ADA) to mibavademab | Up to day 280 |
| Magnitude of ADA to mibavademab | Up to day 280 |
Countries
United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed