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

JRCT ID: jRCT2031230392

Registered date:12/10/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Autosomal Dominant Hypocalcemia Type 1 (ADH1)
• Date of first enrollment: 26/09/2023
• Target sample size: 3
• Countries of recruitment: United States,Japan,Taiwan,Japan,Netherlands,Japan,Italy,Japan,France,Japan,Denmark,Japan,Czech Republic,Japan,Canada,Japan,Brazil,Japan,Australia,Japan
• Study type: Interventional
• Intervention(s): Determined dose of encarelet (CLTX-305) from 4.5 mg, 9 mg, 27 mg or 54 mg is orally administered BID for participants in encarelet group.

Outcome(s)

Primary Outcome

The proportion of responders who meet both of the following criteria at the completion of the maintenance dosing period:
1) cCa within 8.3-10.7 mg/dL and
2) 24-hr UCa within the reference range (<300 mg/day for men, <250 mg/day for women)

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include 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 less than 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 Week 24 (Period 3). 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

Exclude criteria

1. History of hypocalcemic seizure within the past 3 months preceding Screening.
2. History of thyroid or parathyroid surgery.
3. Pregnant or nursing (lactating) women, where pregnancy is confirmed by a positive beta-human chorionic gonadotropin (B-hCG) laboratory test.
4. History of treatment with PTH 1-84 or 1-34 within the 2 months preceding Screening and requiring SoC exceeding more than 1.2x their pre-PTH treatment total daily doses or bone turnover markers, CTx and P1NP, over upper limit of normal for sex, age (men only) and menopausal status (women only).
5. 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.
6. Blood 25-OH Vitamin D level less than 25 ng/mL
7. Estimated glomerular filtration rate (eGFR) less than 30 mL/minute/1.73 m2 using CKD-EPI creatinine equation refit without the race variable (CKD-EPIcr R) (for participants less than 18 years old the Bedside Schwartz equation should be used).
8. 12-lead resting ECG with clinically important abnormalities except for asymptomatic QT interval corrected (QTc) prolongation clinically ascribed to hypocalcemia.
9. 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 more than 12 weeks after completion of HCV therapy may participate in the study
10. Male or female participants planning to conceive a child prior to the LTE
11. Hypersensitivity to any active substance or excipient of encaleret.
12. Presence or history of any disease or condition (eg, drug or alcohol dependency) that, in the view of the Investigator, would affect the participants safety or places the participant at high risk of poor treatment compliance or of not completing the study.

Related Information

• Primary Sponsor: Mathew Arun
• Secondary ID(s): NCT05680818