A Study to Investigate Mibavademab in Adult Women With Functional Hypothalamic Amenorrhea

• Mibavademab (Drug), also known as REGN4461: Administered per the protocol
• Placebo (Other): Administered per the protocol

Primary outcomes

• Change from the highest serum estradiol observed during a 28-day period [Baseline to month 6]

Secondary outcomes

• 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]

Sex: Female, ages: 18 Years to 40 Years

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 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 <23% from rigorous exercise as determined by the investigator through Standard of Care (SoC) methods (eg, skinfold thickness, DXA, bioimpedance) within 6 months of screening

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, as described in the protocol
3. Has uterine (eg, absence of uterus, prior endometrial ablation, endometriosis, outflow tract disorders) or ovarian conditions (eg, absence of an ovary, presence of large polycystic ovaries i.e. greater than 10 cc) 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), as described in the protocol
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/Exclusion criteria apply

• Clinical Trial Management, Study director, Regeneron Pharmaceuticals