ADH1 and ADH2 Disease Monitoring Study (DMS) (CLARIFY)

Autosomal Dominant Hypocalcemia Types 1 And 2 (ADH1/2) Disease Monitoring Study (DMS)

A global, multi-center, Disease Monitoring Study (DMS) in participants with Autosomal Dominant Hypocalcemia Type 1 (ADH1) or Autosomal Dominant Hypocalcemia Type 2 (ADH2) designed to characterize ADH1 and ADH2 disease presentation and progression through retrospective (past) and longitudinal prospective (over time into the future) data collection.

Study Overview

• Status: Active, not recruiting
• Conditions: Autosomal Dominant Hypocalcemia

Detailed Description

The ADH1 and ADH2 DMS is designed to better understand the disease burden of ADH1 and ADH2, how participants with ADH1 or ADH2 are managed with standard of care practices in a real-world setting, and how standard of care treatment impacts ADH1 and ADH2 symptoms.

The study will include adult and pediatric participants with a confirmed clinical diagnosis of ADH1 or ADH2. Each participant's data will be collected over a period of up to 5 years. In addition, retrospective (or past) data will be collected.

• Study Type: Observational
• Enrollment (Actual): 95

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Saint Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
• Belgium
  • Flemish Brabant
    • Leuven, Flemish Brabant, Belgium, 3000
      • Universitaire Ziekenhuizen Leuven
• Canada
  • Ontario
    • Oakville, Ontario, Canada, L6M 1M1
      • Bone Research and Education Centre
• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Hospital (HUS) - The New Children's Hospital
• France
  • Lille, France, 59000
    • CHU de Lille
  • Auvergne-Rhône-Alpes
    • Bron, Auvergne-Rhône-Alpes, France, 69500
      • HCL Hopital Femme Mere Enfant
    • Lyon, Auvergne-Rhône-Alpes, France, 69003
      • HCL Hopital Edouard Herriot
  • Île-de-France Region
    • Le Kremlin-Bicêtre, Île-de-France Region, France, 94270
      • Departement d'Endocrinologie et Diabetes pour Enfants - AP-HP Hopital Bicetre
• Germany
  • Göttingen, Germany, 37075
    • Endokrinologikum Gottingen
• Italy
  • Rome, Italy, 00128
    • Policlinico Universitario Campus Bio-Medico
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • Irccs Ospedale San Raffaele
    • Milan, Lombardy, Italy, 20122
      • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
• Japan
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Tokyo, Japan, 113-8655
    • The University of Tokyo Hospital
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC
• Portugal
  • Lisbon, Portugal, 1649-028
    • Centro Hospitalar Universitario de Lisboa Norte - Hospital de Santa Maria
• United Kingdom
  • Manchester, United Kingdom, M13 9WL
    • Royal Manchester Children's Hospital
• United States
  • California
    • Oakland, California, United States, 94609
      • University of California, San Francisco (UCSF) - Benioff Children's Hospital - Oakland
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University (IU) School of Medicine - University Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • Physician's East Endocrinology
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center (OSUMC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Eligible participants include children (birth to 17 years) and adults (18 - 90 years) with ADH1 or ADH2 as determined by an activating variant of CASR in ADH1 or GNA11 in ADH2.

Description

Key Inclusion Criteria:

• Have a documented activating variant or variant of uncertain significance of the CASR gene causative of ADH1 or documented activating variant or variant of uncertain significance of the GNA11 gene causative of ADH2 associated with a clinical syndrome of hypoparathyroidism prior to enrollment

Note: Acceptable documentation includes CASR or GNA11 genetic analysis report. If no prior documented CASR or GNA11 gene variant or variant of uncertain significance, potential participants can undergo CASR and GNA11 gene variant analysis at Screening.

• Be willing and able to provide informed consent or assent after the nature of the study and its details have been explained, and prior to any research-related procedures
• Be willing and able to provide access to prior medical records including imaging, biochemical, and diagnostic and medical history data, if available
• Be willing and able to comply with the study visit schedule and study procedures

Key Exclusion Criteria:

• Have serious medical or psychiatric comorbidity that, in the opinion of the Investigator, would present a concern for participant safety or compromise the ability to provide consent or assent, or comply with the study visit schedule and study procedures
• Enrollment in an interventional clinical study at the time of DMS Screening visit

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ADH 1/2 DMS; Participants with ADH1 or ADH2. No investigational product will be administered to participants in this study. Participants will only receive standard of care (SoC) treatment as directed by the participants' treating physicians.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood Calcium Homeostasis	Up to 60 months
Phosphorus Homeostasis	Up to 60 months
Magnesium Homeostasis	Up to 60 months
Intact Parathyroid Hormone (iPTH) Homeostasis	Up to 60 months
Mineral Homeostasis as Assessed by 1,25-dihydroxyvitamin D Homeostasis	Up to 60 months
Urine Calcium Homeostasis	Up to 60 months
Urine Phosphorus Homeostasis	Up to 60 months
Urine Magnesium Homeostasis	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Blood Creatinine Levels	Up to 60 months
Estimated Glomerular Filtration Rate (eGFR)	Up to 60 months
Number of Participants With Nephrocalcinosis and Nephrolithiasis as Assessed by Renal Ultrasound	Up to 60 months
Bone Mineral Density as Assessed by Dual-Energy X-Ray Absorptiometry (DXA)	Up to 60 months
Change from Baseline in 36-Item Short Form Health Survey (SF-36v2) Physical Component Score and Mental Component Score in Participants ≥ 16 years	Up to 60 months
Change from Baseline in 10-Item Short-Form 10 Healthy Survey for Children (SF-10) Score in participants ≥ 6 years and <16 years	Up to 60 months
Number of Participants Receiving One or More ADH1/2 Treatment Regimens	Up to 60 months

Collaborators and Investigators

• Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company
• Investigators: Study Director: Calcilytix Medical Director, Calcilytix Therapeutics, Inc., a BridgeBio company

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2022
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: January 18, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Musculoskeletal Diseases; Muscular Diseases; Metabolic Diseases; Hypocalcemia; Hypoparathyroidism; Hypercalciuria; Calcium Sensing Receptor; Autosomal Dominant Hypocalcemia Type 1 (ADH1); Autosomal Dominant Hypocalcemia Type 2 (ADH2); Musculoskeletal Abnormalities; Calcium Metabolism Disorders; Hypocalcemic Seizures; Nephrocalcinosis; Nephrolithiasis; GNA11 mutation; CaSR gene; CaSR gene mutation; CaSR mutation; GNA11 gene; GNA11 gene mutation
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Nervous System Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urolithiasis; Neuromuscular Diseases; Urological Manifestations; Congenital Abnormalities; Water-Electrolyte Imbalance; Parathyroid Diseases; Calcinosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Nephrolithiasis; Muscular Diseases; Musculoskeletal Diseases; Metabolic Diseases; Hypoparathyroidism; Hypocalcemia; Hypercalciuria; Musculoskeletal Abnormalities; Nephrocalcinosis; Calcium Metabolism Disorders; Hypercalciuric Hypocalcemia, Familial
• Other Study ID Numbers: CLTX-305-901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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