Authorised Therapeutic confirmatory (Phase III) Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Clinical study to investigate the Efficacy and Safety of Encaleret Compared to Standard of Care treatment in patients with Autosomal Dominant Hypocalcemia Type 1 (ADH1)

EU CTIS ID: 2022-501398-38-00

What this study is testing

To demonstrate the efficacy of encaleret compared to standard of care (SoC) treatment on albumin-corrected blood calcium (cCa) and 24-hr urinary calcium (UCa) excretion

  • Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • 1. Participant must be at least 18 years of age, at the time of signing the informed consent.
  • 10. Postmenopausal females and females not of childbearing potential may participate in this study without use of contraception: a) Females are considered postmenopausal if they have had 12 months of natural (spontaneous) amenorrhea without an alternative medical cause and must be confirmed with plasma FSH. b) Females are considered not of childbearing potential if they have had surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, shall she be considered not of childbearing potential..
  • 11. Females of childbearing potential, defined as all females physiologically capable of becoming pregnant, must use highly effective methods of contraception starting at Screening and for 3 months following the last dose of encaleret. Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • 12. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
  • 2. Participants must have a documented pathogenic or likely pathogenic activating variant, or variant of uncertain significance, of the CASR gene associated with biochemical findings of hypoparathyroidism either present at Screening or a documented history of both: (...). Note: A genetic analysis report for CASR will be acceptable. In the absence of any documentation for the CASR variant, participants must be willing to undergo CASR variant analysis. Participants who have undergone an allogeneic bone marrow transplant must provide CASR variant analysis report performed prior to the bone marrow transplant Participants who have received a packed red blood cell transfusion must wait 2 weeks following the transfusion before undergoing CASR variant analysis, and participants who have received a whole blood transfusion must wait 4 weeks following the transfusion before undergoing CASR variant analysis.
  • 3. Participants must have a documented history of symptoms or signs of ADH1. Symptoms of ADH1 include agitation, anxiety, back pain, brain fog, bronchospasm, blepharospasm, cardiac failure, cognitive impairment, difficulty focusing/concentration, esophageal spasm, facial spasm, headaches, hypoesthesia (including facial and oral), irritability, laryngospasm, muscle cramping, muscle fatigue, muscle spasms, muscle tightness, muscle twitching, musculoskeletal pain, musculoskeletal stiffness, myalgia, nephrolithiasis, nervousness, paresthesia (including oral), polydipsia, polyuria, seizure, tetany, throat tightness, or tremor. Signs of ADH1 include basal ganglia or other cerebral calcification, Chvostek sign, hypercalciuria, nephrocalcinosis, papilledema, premature cataracts, prolonged QT interval on ECG, pseudotumor cerebri, or Trousseau sign

You likely can't join if

  • 1. History of hypocalcemic seizure within the past 3 months preceding Screening.
  • 3. History of the following within 5 years of screening: cancer except thyroid cancer, basal cell skin cancer or squamous cell skin cancer, patients with skeletal malignancies or bone metastases or irradiation (radiotherapy) to the skeleton.
  • 4. History of renal transplantation.
  • 5. Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (β-hCG) laboratory test.
  • 6. History of treatment with 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, CTx and P1NP, > upper limit of normal for sex, age (men only) and menopausal status (women only).
  • 7. Received any investigational medicinal product other than encaleret within 30 days or 5 half-lives, whichever is longer, prior to the first day on study, or are in follow-up for another interventional clinical study during Screening. If the half-life of an investigational medicinal product is unknown, then 30 days prior to Screening..
See the full eligibility criteria
Who can join
  • 1. Participant must be at least 18 years of age, at the time of signing the informed consent.
  • 10. Postmenopausal females and females not of childbearing potential may participate in this study without use of contraception: a) Females are considered postmenopausal if they have had 12 months of natural (spontaneous) amenorrhea without an alternative medical cause and must be confirmed with plasma FSH. b) Females are considered not of childbearing potential if they have had surgical bilateral oophorectomy (with or without hysterectomy) or hysterectomy. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, shall she be considered not of childbearing potential..
  • 11. Females of childbearing potential, defined as all females physiologically capable of becoming pregnant, must use highly effective methods of contraception starting at Screening and for 3 months following the last dose of encaleret. Contraceptive use by males and females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • 12. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
  • 2. Participants must have a documented pathogenic or likely pathogenic activating variant, or variant of uncertain significance, of the CASR gene associated with biochemical findings of hypoparathyroidism either present at Screening or a documented history of both: (...). Note: A genetic analysis report for CASR will be acceptable. In the absence of any documentation for the CASR variant, participants must be willing to undergo CASR variant analysis. Participants who have undergone an allogeneic bone marrow transplant must provide CASR variant analysis report performed prior to the bone marrow transplant Participants who have received a packed red blood cell transfusion must wait 2 weeks following the transfusion before undergoing CASR variant analysis, and participants who have received a whole blood transfusion must wait 4 weeks following the transfusion before undergoing CASR variant analysis.
  • 3. Participants must have a documented history of symptoms or signs of ADH1. Symptoms of ADH1 include agitation, anxiety, back pain, brain fog, bronchospasm, blepharospasm, cardiac failure, cognitive impairment, difficulty focusing/concentration, esophageal spasm, facial spasm, headaches, hypoesthesia (including facial and oral), irritability, laryngospasm, muscle cramping, muscle fatigue, muscle spasms, muscle tightness, muscle twitching, musculoskeletal pain, musculoskeletal stiffness, myalgia, nephrolithiasis, nervousness, paresthesia (including oral), polydipsia, polyuria, seizure, tetany, throat tightness, or tremor. Signs of ADH1 include basal ganglia or other cerebral calcification, Chvostek sign, hypercalciuria, nephrocalcinosis, papilledema, premature cataracts, prolonged QT interval on ECG, pseudotumor cerebri, or Trousseau sign
  • 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 must discontinue the phosphate binders (other than calcium salts) at least one day prior to 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 Section 5.4.1.
  • 9. Male participants with women of childbearing potential (WOCBP) partners must use acceptable contraceptive methods as defined in Section 7.7.2.
What rules you out
  • 1. History of hypocalcemic seizure within the past 3 months preceding Screening.
  • 3. History of the following within 5 years of screening: cancer except thyroid cancer, basal cell skin cancer or squamous cell skin cancer, patients with skeletal malignancies or bone metastases or irradiation (radiotherapy) to the skeleton.
  • 4. History of renal transplantation.
  • 5. Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (β-hCG) laboratory test.
  • 6. History of treatment with 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, CTx and P1NP, > upper limit of normal for sex, age (men only) and menopausal status (women only).
  • 7. Received any investigational medicinal product other than encaleret within 30 days or 5 half-lives, whichever is longer, prior to the first day on study, or are in follow-up for another interventional clinical study during Screening. If the half-life of an investigational medicinal product is unknown, then 30 days prior to Screening..
  • 8. Blood 25-OH Vitamin D level <25 ng/mL If participant has a blood 25-OH Vitamin D level <25 ng/mL at the Screening Visit, they will be prescribed cholecalciferol or ergocalciferol supplementation per the Investigator. Once the 25-OH Vitamin D level is ≥ 25 ng/mL, the participant will be eligible to proceed with SoC Optimization (if still within Screening window of up to 84 days total) or re-screen for the study.
  • 9. Estimated glomerular filtration rate <30 mL/minute/1.73 m2 using CKD-EPIcr_R. See Appendix C.
  • 17. Presence or history of any disease or condition (eg, drug or alcohol dependency) that, in the view of the Investigator, would affect the participant’s safety or places the participant at high risk of poor treatment compliance or of not completing the study.
  • 10. 12-lead resting ECG with clinically important abnormalities except for asymptomatic QTc prolongation clinically ascribed to hypocalcemia.
  • 11. Participants with positive Hepatitis B surface antigen (HBbsAg), 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.
  • 12. Male or female participants planning to conceive a child prior to the LTE.
  • 13. Hypersensitivity to any active substance or excipient of encaleret. See Section 7.2.1 for list of active ingredients and excipients.
  • 14. Any current disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism.
  • 15. Current treatment with cardiac glycosides (because hypercalcemia of any cause may predispose to digitalis toxicity).
  • 16. Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase-isomaltase insufficiency.
  • 2. History of thyroid or parathyroid surgery.

The study team makes the final eligibility decision.

Where it's taking place

  • Australia
  • United States
  • Canada
  • Brazil
  • Taiwan
  • Japan

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Australia; United States; Canada; Brazil; Taiwan; Japan. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.