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

A Phase 2, Double-Blind, Placebo-Controlled Study to Investigate the Safety and Efficacy of Mibavademab in Adult Women With Functional Hypothalamic Amenorrhea

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)

Study Overview

• Status: Recruiting
• Conditions: Functional Hypothalamic Amenorrhea (FHA)
• Intervention / Treatment: Drug: Mibavademab; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Recruiting
      • Arensia Exploratory Medicine Clinic
  • California
    • West Hills, California, United States, 91307
      • Recruiting
      • Focus Clinical Research
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University (OHSU)
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16507
      • Recruiting
      • OBGYN Associates of Erie
  • Texas
    • Houston, Texas, United States, 77082
      • Recruiting
      • Zillan Clinical Research
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Tidewater Clinical Research - Tidewater Physicians for Women

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

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/Exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Administered per the protocol
Experimental: Mibavademab	Drug: Mibavademab; Administered per the protocol; Other Names: REGN4461

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from the highest serum estradiol observed during a 28-day period	Baseline to month 6

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2026
• Primary Completion (Estimated): August 20, 2027
• Study Completion (Estimated): December 8, 2027

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 19, 2025

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Secondary amenorrhea; Hypothalamic-Pituitary-Ovarian (HPO) axis; Group I ovulation disorder; Hypogonadotropic hypogonadal anovulation
• Other Study ID Numbers: R4461-FHA-2485

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No