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

Last updated: March 11, 2025
Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company
Overall Status: Active - Not Recruiting

Phase

3

Condition

Parathyroid Disorders

Hypoparathyroidism

Treatment

Encaleret

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

Standard of Care

Clinical Study ID

NCT05680818
CLTX-305-302
  • Ages > 16
  • All Genders

Study 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

Inclusion

Key Inclusion Criteria:

  1. Participants must have a documented pathogenic or likely pathogenic activatingvariant, 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 thethiazide is being used as an antihypertensive, alternative therapy will beprescribed by the Investigator as needed.

  5. Participants treated with phosphate binders (other than calcium salts) mustdiscontinue the phosphate binders at least one day prior to the SoC OptimizationVisit 1.

  6. Participants treated with magnesium or potassium supplements must be willing todiscontinue such treatment prior to the first dose of encaleret.

  7. Participants treated with potassium-sparing diuretics must be willing to discontinuesuch treatment prior to the first dose of encaleret.

  8. Participants must meet SoC Optimization criteria as defined in the protocol.

Exclusion

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 positivebeta-human chorionic gonadotropin (β-hCG) laboratory test.

  5. History of treatment with parathyroid hormone (PTH) 1-84 or 1-34 within the 2 monthspreceding Screening and requiring SoC doses exceeding >1.2× their pre-PTH treatmenttotal 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 chronickidney disease-EPI creatinine equation refit without the race variable (chronickidney disease-EPI creatinine equation refit without the race variable [CKD-EPIcr_R]) (for participants <18 years old the Bedside Schwartz equation shouldbe used).

  8. Participants with positive Hepatitis B surface antigen (HBsAg), Hepatitis Aimmunoglobulin M (IgM), or human immunodeficiency virus (HIV) viral serology test atthe Screening Visit. Participants who are in complete remission from Hepatitis Cvirus (HCV) as evidenced by sensitive assay ≥12 weeks after completion of HCVtherapy may participate in the study.

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

Study Design

Total Participants: 67
Treatment Group(s): 3
Primary Treatment: Encaleret
Phase: 3
Study Start date:
January 06, 2023
Estimated Completion Date:
September 30, 2028

Study 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.

Connect with a study center

  • Royal North Shore Hospital

    Saint Leonards, New South Wales 2065
    Australia

    Site Not Available

  • Royal Brisbane and Women's Hospital

    Herston, Queensland 4029
    Australia

    Site Not Available

  • Bone Research & Education Centre

    Oakville, Ontario L6M 1M1
    Canada

    Site Not Available

  • Vseobecna fakultni nemocnice v Praze

    Nové Město, 128 08
    Czechia

    Site Not Available

  • Aarhus University Hospital

    Aarhus, 8200
    Denmark

    Site Not Available

  • CHU Bicetre

    Le Kremlin-Bicêtre, 94270
    France

    Site Not Available

  • Hôpital Edouard Herriot - HCL

    Lyon, 69003
    France

    Site Not Available

  • IRCCS Ospedale San Raffaele

    Milano, 20132
    Italy

    Site Not Available

  • University Hospital of Pisa

    Pisa, 56124
    Italy

    Site Not Available

  • Fondazione Policlinico Universitario Campus Bio-Medico

    Roma, 00128
    Italy

    Site Not Available

  • Osaka University Hospital

    Osaka, 565-0871
    Japan

    Site Not Available

  • The University of Tokyo Hospital

    Tokyo, 113-8655
    Japan

    Site Not Available

  • Eramus MC

    Rotterdam, 3015 AA
    Netherlands

    Site Not Available

  • National Cheng Kung University Hospital

    Tainan, 70428
    Taiwan

    Site Not Available

  • Freeman Hospital

    Newcastle Upon Tyne, NE7 7DN
    United Kingdom

    Site Not Available

  • Norfolk and Norwich University Hospital

    Norwich, NR4 7UY
    United Kingdom

    Site Not Available

  • UCSF Benioff Children's Hospital, Oakland

    Oakland, California 94609
    United States

    Site Not Available

  • Children's Hospital Colorado

    Aurora, Colorado 80045
    United States

    Site Not Available

  • University of Chicago - Medical Center

    Chicago, Illinois 60637
    United States

    Site Not Available

  • Indiana University Health University Hospital

    Indianapolis, Indiana 46202
    United States

    Site Not Available

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland 21287
    United States

    Site Not Available

  • NIH

    Bethesda, Maryland 20892
    United States

    Site Not Available

  • Boston Children's Hospital

    Boston, Massachusetts 02115
    United States

    Active - Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts 02114
    United States

    Site Not Available

  • Mayo Clinic - Rochester

    Rochester, Minnesota 55905
    United States

    Site Not Available

  • Columbia University Irving Medical Center

    New York, New York 10032
    United States

    Site Not Available

  • Physicians East

    Greenville, North Carolina 27834
    United States

    Site Not Available

  • Ohio State University Medical Center

    Columbus, Ohio 43203
    United States

    Site Not Available

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Site Not Available

  • Houston Methodist Hospital

    Houston, Texas 77030
    United States

    Site Not Available

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