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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05680818
Other study ID # CLTX-305-302
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date January 6, 2023
Est. completion date September 2028

Study information

Verified date May 2024
Source Calcilytix Therapeutics, Inc., a BridgeBio company
Contact Medical Information
Phone 650.600.3610
Email MedInfo@bridgebio.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


Description:

ADH1 is a rare genetic form of hypoparathyroidism. ADH1 may be passed down from affected parents to their children. The main portion of the study is divided into a Screening Period and 3 Periods followed by an optional Long-Term Extension (LTE). The estimated duration of this main portion of the study is approximately 12 months. The duration of the LTE is approximately 48 months. Participants will enter an up-to-6-week Screening period and once confirmation of all Inclusion/Exclusion criteria transition into an up-to-15-week standard of care (SoC) optimization phase. The eligible participants will enter Period 1 after completing the SoC optimization phase. Period 1 is the 4-week SoC Maintenance period of the study during which the SoC dose will only be adjusted to address potential safety concerns such as hypocalcemia or hypercalcemia. After completion of Period 1, eligible participants will enter Period 2 and will be randomized to receive either encaleret or SoC treatment for 20 weeks. Both the investigator and participant will know whether the participant was randomized to the encaleret treatment arm or SoC treatment arm. During Period 2, encaleret or SoC will be adjusted based on blood calcium levels. After completion of Period 2, participants will proceed to Period 3, the 4-week dose maintenance period. Following completion of Period 3, participants from CLTX-305-302 may enter the LTE. Those who completed CLTX-305-201 (NCT04581629) are also eligible to continue in the LTE. Participants will receive encaleret treatment for approximately 48 months, or 72 months for participants who transitioned from CLTX-305-201, or until a participant has access to commercial encaleret, or the Sponsor decides to end the study, whichever occurs first.


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date September 2028
Est. primary completion date April 2025
Accepts healthy volunteers No
Gender All
Age group 16 Years and older
Eligibility 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 (ß-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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Encaleret
Administered as film-coated tablet for oral use
Dietary Supplement:
Standard of Care
Calcium supplements and/or active Vitamin D (calcitriol, alfacalcidol, falecalcitriol, etc.)

Locations

Country Name City State
Australia Royal Brisbane and Women's Hospital Herston Queensland
Australia Royal North Shore Hospital Saint Leonards New South Wales
Canada Bone Research & Education Centre Oakville Ontario
Czechia Vseobecna fakultni nemocnice v Praze Nové Mesto
Denmark Aarhus University Hospital Aarhus
France CHU Bicetre Le Kremlin-Bicêtre
France Hôpital Edouard Herriot - HCL Lyon
Italy IRCCS Ospedale San Raffaele Milano
Italy University Hospital of Pisa Pisa
Italy Fondazione Policlinico Universitario Campus Bio-Medico Roma
Japan Osaka University Hospital Osaka
Japan The University of Tokyo Hospital Tokyo
Netherlands Eramus MC Rotterdam
Taiwan National Cheng Kung University Hospital Tainan
United Kingdom Freeman Hospital Newcastle Upon Tyne
United States Children's Hospital Colorado Aurora Colorado
United States NIH Bethesda Maryland
United States Boston Children's Hospital Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States Ohio State University Medical Center Columbus Ohio
United States Physicians East Greenville North Carolina
United States Houston Methodist Hospital Houston Texas
United States Indiana University Health University Hospital Indianapolis Indiana
United States Columbia University Irving Medical Center New York New York
United States UCSF Benioff Children's Hospital, Oakland Oakland California
United States The Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Mayo Clinic - Rochester Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Calcilytix Therapeutics, Inc., a BridgeBio company

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Czechia,  Denmark,  France,  Italy,  Japan,  Netherlands,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 (2.1-2.7 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 Number of Participants With Intact Parathyroid Hormone (iPTH) Within or Greater than the Reference Range Up to Week 24
Secondary Number of Participants who Achieve Blood Magnesium Within the Reference Range Up to Week 24
Secondary Number of Participants who Achieve Blood Phosphate Within the Reference Range Up to Week 24
Secondary Change From Baseline in Blood 1,25-(OH)2 Vitamin D Baseline to Week 24
Secondary Change From Baseline in cCa Baseline to Week 24
Secondary Change From Baseline in 24-hour UCa Baseline to Week 24
Secondary Change From Baseline in iPTH Baseline to Week 24
Secondary Change From Baseline in Blood Phosphate and Blood Magnesium Baseline to Week 24
Secondary Change From Baseline in Urine Magnesium, Phosphate, Sodium, and Citrate Handling Baseline to Week 24
Secondary Change From Baseline in QT Interval Corrected for Changes in the Heart Rate With Fridericia Formula (QTcF) as Assessed by Electrocardiogram (ECG) Baseline to Week 24
Secondary 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 Baseline to Week 24
Secondary Number of Participants in the Encaleret Arm Receiving Calcium and/or Vitamin D Supplements Up to Week 24
Secondary Steady State Encaleret Trough Concentration (Ctrough) Up to Week 24
See also
  Status Clinical Trial Phase
Completed NCT04581629 - Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1 Phase 2
Completed NCT02204579 - A Study to Determine the Effects of NPSP795 on the Calcium-sensing Receptor in Subjects With Autosomal Dominant Hypocalcemia as Measured by PTH Levels and Blood Calcium Concentrations Phase 2