Clinical trial NCT05680818: Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With ADH1
Official title: CALIBRATE: A Phase 3, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Encaleret Compared to Standard of Care in Participants With Autosomal Dominant Hypocalcemia Type 1 (ADH1)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2023-01-11
Enrollment: 67
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


Eligibility criteria: Key Inclusion Criteria:

1. 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.
2. Participants must have a documented history of symptoms or signs of ADH1.
3. Participants 16 to \<18 years old must have closed growth plates on hand radiograph.
4. 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.
5. 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.
6. Participants treated with magnesium or potassium supplements must be willing to discontinue such treatment prior to the first dose of encaleret.
7. Participants treated with potassium-sparing diuretics must be willing to discontinue such treatment prior to the first dose of encaleret.
8. Participants must meet SoC Optimization criteria as defined in the protocol.

Key Exclusion Criteria:

1. History of hypocalcemic seizure within the past 3 months preceding Screening.
2. History of thyroid or parathyroid surgery.
3. History of renal transplantation.
4. Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (β-hCG) laboratory test.
5. 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).
6. Blood 25-OH Vitamin D level \<25 nanograms (ng)/milliliter (mL).
7. 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).
8. 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.

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

Primary outcomes:
measure: Number of Responders who Achieve Both Albumin-Corrected Blood Calcium (cCa) and 24-hour Urinary Calcium (UCa) Within the Target Range
timeFrame: Up to Week 24
Secondary outcomes:
measure: Number of Participants With Intact Parathyroid Hormone (iPTH) Within or Greater than the Reference Range
timeFrame: Up to Week 24
measure: Number of Participants who Achieve Blood Magnesium Within the Reference Range
timeFrame: Up to Week 24
measure: Number of Participants who Achieve Blood Phosphate Within the Reference Range
timeFrame: Up to Week 24
measure: Change From Baseline in Blood 1,25-(OH)2 Vitamin D
timeFrame: Baseline to Week 24
measure: Change From Baseline in cCa
timeFrame: Baseline to Week 24
measure: Change From Baseline in 24-hour UCa
timeFrame: Baseline to Week 24
measure: Change From Baseline in iPTH
timeFrame: Baseline to Week 24
measure: Change From Baseline in Blood Phosphate and Blood Magnesium
timeFrame: Baseline to Week 24
measure: Change From Baseline in Urine Magnesium, Phosphate, Sodium, and Citrate Handling
timeFrame: Baseline to Week 24
measure: Change From Baseline in QT Interval Corrected for Changes in the Heart Rate With Fridericia Formula (QTcF) as Assessed by Electrocardiogram (ECG)
timeFrame: Baseline to Week 24
measure: Change from Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Score and Mental Component Score and Each of the Sub-Domains
timeFrame: Baseline to Week 24
measure: Number of Participants in the Encaleret Arm Receiving Calcium and/or Vitamin D Supplements
timeFrame: Up to Week 24
measure: Steady State Encaleret Trough Concentration (Ctrough)
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital, Oakland
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University Health University Hospital
state: Indiana
city: Bethesda
country: United States
facility: NIH
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Greenville
country: United States
facility: Physicians East
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Oakville
country: Canada
facility: Bone Research & Education Centre
state: Ontario
city: Nové Město
country: Czechia
facility: Vseobecna fakultni nemocnice v Praze
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Le Kremlin-Bicêtre
country: France
facility: CHU Bicetre
city: Lyon
country: France
facility: Hôpital Edouard Herriot - HCL
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
city: Pisa
country: Italy
facility: University Hospital of Pisa
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Campus Bio-Medico
city: Tokyo
country: Japan
facility: The University of Tokyo Hospital
city: Rotterdam
country: Netherlands
facility: Eramus MC
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
Study officials:
affiliation: Calcilytix Therapeutics, Inc., a BridgeBio company
name: Calcilytix Medical Director
role: STUDY_DIRECTOR
References: