Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1

NCT05680818 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: CLTX-305-302
• Study Type: interventional
• Target: 67
• Locations: 10 countries
• Sites: 25

Brief Summary

The primary purpose of the study is to understand the effectiveness, safety, and tolerability of encaleret when compared to standard of care (SoC) treatment in participants with Autosomal Dominant Hypocalcemia Type 1 (ADH1).

Conditions

Autosomal Dominant Hypocalcemia (ADH)

Keywords

Autosomal Dominant Hypocalcemia Type 1 (ADH1); Hypocalcemia; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Calcium Metabolism Disorders; Metabolic Diseases; Hypoparathyroidism; Hypocalcemic Seizures; Hypercalciuria; Nephrocalcinosis; Nephrolithiasis; Calcium Sensing Receptor; Encaleret; Hypopara

Outcome Measures

Primary Outcomes (1)

• Number of Responders who Achieve Both Albumin-Corrected Blood Calcium (cCa) and 24-hour Urinary Calcium (UCa) Within the Target Range

  * cCa within 8.3-10.7 mg/dL (2.08-2.68 millimoles per liter \[mmol/L\]) * 24-hr UCa within the reference range (\< 300 mg/day for men \[7.5 mmol/day\], \< 250 mg/day for women \[6.25 mmol/day\])

  Up to Week 24

Secondary Outcomes (13)

• Number of Participants With Intact Parathyroid Hormone (iPTH) Within or Greater than the Reference Range

  Up to Week 24

• Number of Participants who Achieve Blood Magnesium Within the Reference Range

  Up to Week 24

• Number of Participants who Achieve Blood Phosphate Within the Reference Range

  Up to Week 24

• Change From Baseline in Blood 1,25-(OH)2 Vitamin D

  Baseline to Week 24

• Change From Baseline in cCa

  Baseline to Week 24

Study Arms (2)

Encaleret

EXPERIMENTAL

Participants will receive encaleret at a dose as needed based on calcium levels.

Drug: Encaleret

Standard of Care (SoC)

OTHER

Participants will continue receiving calcium supplements and/or active Vitamin D (calcitriol, alfacalcidol, falecalcitriol, etc.)

Dietary Supplement: Standard of Care

Interventions

Encaleret DRUG

Administered as film-coated tablet for oral use

Also known as: CLTX-305, Encaleret Sulfate

Encaleret

Standard of Care DIETARY_SUPPLEMENT

Calcium supplements and/or active Vitamin D (calcitriol, alfacalcidol, falecalcitriol, etc.)

Standard of Care (SoC)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a documented pathogenic or likely pathogenic activating variant, or variant of uncertain significance, of the calcium sensing receptor (CASR) gene associated with biochemical findings of hypoparathyroidism.
• Participants must have a documented history of symptoms or signs of ADH1.
• Participants 16 to \<18 years old must have closed growth plates on hand radiograph.
• Participants treated with thiazide diuretics must discontinue thiazides for at least 14 days prior to SoC Optimization Visit 1 through Week 24 (Period 3). When the thiazide is being used as an antihypertensive, alternative therapy will be prescribed by the Investigator as needed.
• Participants treated with phosphate binders (other than calcium salts) must discontinue the phosphate binders at least one day prior to the SoC Optimization Visit 1.
• Participants treated with magnesium or potassium supplements must be willing to discontinue such treatment prior to the first dose of encaleret.
• Participants treated with potassium-sparing diuretics must be willing to discontinue such treatment prior to the first dose of encaleret.
• Participants must meet SoC Optimization criteria as defined in the protocol.

You may not qualify if:

• History of hypocalcemic seizure within the past 3 months preceding Screening.
• History of thyroid or parathyroid surgery.
• History of renal transplantation.
• Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (β-hCG) laboratory test.
• History of treatment with parathyroid hormone (PTH) 1-84 or 1-34 within the 2 months preceding Screening and requiring SoC doses exceeding \>1.2× their pre-PTH treatment total daily doses or bone turnover markers, Collagen cross-linked C-telopeptide (CTx )and Procollagen type 1 N-propeptide (P1NP), \> upper limit of normal for sex, age (men only) and menopausal status (women only).
• Blood 25-OH Vitamin D level \<25 nanograms (ng)/milliliter (mL).
• Estimated glomerular filtration rate (eGFR) \<30 mL/minute/1.73 m\^2 using chronic kidney disease-EPI creatinine equation refit without the race variable (chronic kidney disease-EPI creatinine equation refit without the race variable \[CKD-EPIcr\_R\]) (for participants \<18 years old the Bedside Schwartz equation should be used).
• Participants with positive Hepatitis B surface antigen (HBsAg), Hepatitis A immunoglobulin M (IgM), or human immunodeficiency virus (HIV) viral serology test at the Screening Visit. Participants who are in complete remission from Hepatitis C virus (HCV) as evidenced by sensitive assay ≥12 weeks after completion of HCV therapy may participate in the study.

Sponsors & Collaborators

• Calcilytix Therapeutics, Inc., a BridgeBio company: lead

Study Sites (25)

UCSF Benioff Children's Hospital, Oakland

Oakland, California, 94609, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Indiana University Health University Hospital

Indianapolis, Indiana, 46202, United States

Location

NIH

Bethesda, Maryland, 20892, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Physicians East

Greenville, North Carolina, 27834, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43203, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Royal Brisbane and Women's Hospital

Herston, Queensland, 4029, Australia

Location

Bone Research & Education Centre

Oakville, Ontario, L6M 1M1, Canada

Location

Vseobecna fakultni nemocnice v Praze

New Town, 128 08, Czechia

Location

Aarhus University Hospital

Aarhus, 8200, Denmark

Location

CHU Bicetre

Le Kremlin-Bicêtre, 94270, France

Location

Hôpital Edouard Herriot - HCL

Lyon, 69003, France

Location

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

Location

University Hospital of Pisa

Pisa, 56124, Italy

Location

Fondazione Policlinico Universitario Campus Bio-Medico

Roma, 00128, Italy

Location

The University of Tokyo Hospital

Tokyo, 113-8655, Japan

Location

Eramus MC

Rotterdam, 3015 AA, Netherlands

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Norfolk and Norwich University Hospital

Norwich, NR4 7UY, United Kingdom

Location

MeSH Terms

Conditions

Hypercalciuric Hypocalcemia, Familial; Hypocalcemia; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Calcium Metabolism Disorders; Metabolic Diseases; Hypoparathyroidism; Hypercalciuria; Nephrocalcinosis; Nephrolithiasis

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Water-Electrolyte Imbalance; Neuromuscular Diseases; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Parathyroid Diseases; Endocrine System Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Calcinosis; Urolithiasis

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Calcilytix Medical Director

  Calcilytix Therapeutics, Inc., a BridgeBio company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2022
• First Posted: January 11, 2023
• Study Start: January 6, 2023
• Primary Completion: August 22, 2025
• Study Completion (Estimated): August 1, 2029
• Last Updated: June 11, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); CZ (1); DK (1); FR (2); GB (2); CA (1); AU (2); JP (1); NL (1); IT (3)