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

• Status: Recruiting
• Trial end date: 2028-12-15
• Target enrollment: 0
• Participant gender: All

Summary

A global, multi-center, 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)

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Calcilytix Therapeutics, Inc., a BridgeBio company
• Treatments: 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3; Alfacalcidol; Calcitriol; Calcium; Hydroxycholecalciferols; Vitamin D

Criteria

Inclusion Criteria:

1. Participant must be at least 16 years of age, at the time of signing the informed consent or assent.

2. Participants must have a documented pathogenic activating variant, or variant of uncertain significance, of the CASR gene associated with biochemical findings of hypoparathyroidism

3. Participants must have a documented history of symptoms or signs of ADH1.

4. Participants 16 to <18 years old must have closed growth plates on hand radiograph.

5. Participants treated with thiazide diuretics must discontinue thiazides for at least 14 days prior to Screening through Period 3 Week 24. When the thiazide is being used as an antihypertensive, alternative therapy will be prescribed by the Investigator as needed.

6. Participants treated with phosphate binders must discontinue the phosphate binders at least one day prior to the Screening Visit.

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

8. Participants treated with potassium-sparing diuretics must be willing to discontinue such treatment prior to the first dose of encaleret.

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

10. Male participants must use a highly effective contraceptive method (eg, condoms with spermicidal gel or foam) during vaginal intercourse and should not father a child nor donate sperm while taking encaleret and for 3 months after the last dose of encaleret. Condoms are not required if the participant is vasectomized or if the participant's partner is not a female of childbearing potential.

11. Postmenopausal females and females not of childbearing potential may participate in this study without use of contraception

12. Females of childbearing potential, defined as all females physiologically capable of becoming pregnant, must use two highly effective methods of contraception starting at Screening and for 3 months following the last dose of encaleret.

13. Capable of giving signed informed consent or assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion Criteria:

1. cCa and 24-hr UCa both within the respective reference ranges (cCa = 8.6-10.5 mg/dL in participants 16 to <18 years or 8.5-10.5 mg/dL in participants ≥ 18 years and 24-hr UCa <250 mg/day for women and <300 mg/day for men) at Screening Visit.

2. History of hypocalcemic seizure within the past 3 months preceding Screening.

3. History of thyroid or parathyroid surgery.

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 PTH 1-84 or 1-34 within the 2 months preceding Screening and requiring SoC 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).

6. 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.

7. Blood 25-OH Vitamin D level <25 ng/mL

8. Estimated glomerular filtration rate (eGFR) <30 mL/minute/1.73 m2 using CKD-EPI creatinine equation refit without the race variable (CKD-EPIcr_R) (for participants <18 years old the Bedside Schwartz equation should be used).

9. 12-lead resting ECG with clinically important abnormalities except for asymptomatic QT interval corrected (QTc) prolongation clinically ascribed to hypocalcemia.

10. 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

11. Male or female participants planning to conceive a child prior to the LTE

12. Hypersensitivity to any active substance or excipient of encaleret.

13. 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.