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

NCT04581629 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CLTX-305-201
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Periods 1, 2 and 3: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Adverse events (AEs) were defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. Treatment-emergence was defined as any AE(s) regardless of relationship to investigational medicinal product (IMP), that had an onset or worsened in severity on or after the first dose of IMP.

  Day 1 up to 16 months

• Period 3: Change From Baseline in Albumin-Corrected Blood Calcium Concentrations (cCa)

  Baseline, Week 24

• Period 3: Rate of Urinary Calcium Excretion

  Week 24

Secondary Outcomes (16)

• Periods 1 and 2: Intact Parathyroid Hormone (iPTH) Concentrations in the Blood

  15 minutes pre-dose on Day 5 of Periods 1 and 2 (Periods were 5 days)

• Periods 1 and 2: Area Under the Concentration-Time Curve Extrapolated to Infinity (AUC0-inf) of Encaleret

  Periods 1 and 2: Day 5 (Periods were 5 days)

• Periods 1, 2 and 3: Maximum Plasma Concentration (Cmax) of Encaleret

  Periods 1 and 2: Day 5, Period 3: Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)

• Periods 1, 2 and 3: Time to Maximum Plasma Concentration (Tmax) of Encaleret

  Periods 1 and 2: Day 5; Period 3: Week 24 (Period was 5 days for Periods 1 and 2; 24 weeks for Period 3)

• Periods 2 and 3: Change From Baseline in Blood Calcium Concentration (cCa)

  Period 2: Baseline, Day 5 (Period was 5 days), Period 3: Baseline, Week 24 (Period was 24 weeks)

Study Arms (2)

Cohort 1: Ascending + Steady-State Dose

EXPERIMENTAL

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.

Drug: Encaleret

Cohort 2: Steady-State Dose

EXPERIMENTAL

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.

Drug: Encaleret

Interventions

Encaleret DRUG

Tablets administered orally

Also known as: CLTX-305

Cohort 1: Ascending + Steady-State Dose; Cohort 2: Steady-State Dose

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Calcilytix Therapeutics, Inc., a BridgeBio company: lead

Study Sites (1)

National Institutes of Health (NIH) Clinical Center

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Hypercalciuric Hypocalcemia, Familial

Results Point of Contact

• Title: Medical Information
• Organization: Calcilytix Therapeutics, Inc., a BridgeBio company

MedInfo@bridgebio.com

650.600.3610

Study Officials

• Calcilytix Medical Director

  Calcilytix Therapeutics, Inc., a BridgeBio company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2020
• First Posted: October 9, 2020
• Study Start: September 20, 2020
• Primary Completion: September 7, 2023
• Study Completion: September 7, 2023
• Last Updated: November 19, 2024
• Results First Posted: November 19, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)