Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1

Calcilytix Therapeutics

Status and phase: Completed; Phase 2

Conditions: Autosomal Dominant Hypocalcemia Type 1 (ADH1); Autosomal Dominant Hypocalcemia (ADH)

Treatments: Drug: Encaleret

Study type: Interventional

Funder types: Industry

Identifiers

NCT04581629

CLTX-305-201

Details and patient eligibility

About

The primary purpose of this study is to evaluate the safety, tolerability and effectiveness of encaleret in participants with Autosomal Dominant Hypocalcemia Type 1 (ADH1).

Enrollment: 13 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Be able to understand and sign a written informed consent or assent form, which must be obtained prior to initiation of study procedures.
• Postmenopausal women are allowed to participate in this study
• Body mass index (BMI) ≥ 18.5 to < 39 kilograms (kg)/square meter (m^2)
• Have an activating mutation of the Calcium-sensing receptor (CASR) gene
• Participants being treated with thiazide diuretics may be enrolled if they are willing and able to discontinue thiazides
• Participants being treated with strong Cytochrome P3A4 (CYP3A4) inhibitors should ideally, if clinically appropriate, discontinue these medications during the screening period
• Participants being treated with magnesium or potassium citrate supplements should discontinue such treatment starting on Day -1 during Period 1 and Period 2 and may be asked to discontinue treatment during Period 3

Key Exclusion Criteria:

• History of treatment with parathyroid hormone (PTH) 1-84 or 1-34 within the previous 3 months
• History of hypocalcemic seizure within the past 3 months
• Blood 25-OH Vitamin D level < 25 nanograms (ng)/milliliter (mL)
• Participants with hemoglobin (Hgb) < 13 grams (g)/deciliter (dL) for men and < 12 g/dL for women
• Estimated glomerular filtration rate (eGFR) < 25 mL/minute/1.73 m^2 using Chronic Kidney Disease Epidemiology Collaboration (for participants <18 years old the Schwartz equation will be calculated)
• 12-lead resting electrocardiogram (ECG) with clinically significant abnormalities
• Participants with positive hepatitis B surface antigen (HBsAg), hepatitis A immunoglobulin M (IgM), or human immunodeficiency virus (HIV) viral serology test results at the Screening Visit
• Pregnant or nursing (lactating) women
• History of drug or alcohol dependency within 12 months preceding the Screening Visit
• History of thyroid or parathyroid surgery
• Current participation in other investigational drug studies
• Unwillingness to refrain from blood donation within 12 weeks prior to Screening Visit from the start of the study enrollment through one year after the last dose of the study drug

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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13 participants in 2 patient groups

Cohort 1: Ascending + Steady-State Dose

Experimental group

Description:

Period 1: Participants will receive an ascending dose of encaleret once daily for the first 3 days. Participants will then receive an individualized dose of encaleret twice daily for 2 days. Period 2: Participants will receive encaleret twice daily for 5 days at a single dose level based on responses from Period 1. Period 3: After completion of Period 2, participants will be eligible to receive encaleret for an additional 24 weeks. Long-Term Extension (LTE): At the end of the study, participants will also have an option to receive encaleret for up to an additional 2 years.

Treatment:

Drug: Encaleret

Cohort 2: Steady-State Dose

Experimental group

Description:

Participants will directly be enrolled into Period 2, and receive encaleret twice daily at a dose based on data and responses from Cohort 1 Period 1. Period 2: Participants will receive encaleret twice daily for 5 days. Period 3: After completion of Period 2, participants will be eligible to receive encaleret for an additional 24 weeks. LTE: At the end of the study, participants will also have an option to receive encaleret for up to an additional 2 years.

Treatment:

Drug: Encaleret