- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04581629
Safety, Tolerability, and Efficacy of Encaleret in Participants With Autosomal Dominant Hypocalcemia (ADH) Type 1
A Phase 2b, Open-label Dose-ranging Study Evaluating the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics, and Efficacy of CLTX-305 (Encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Autosomal dominant hypocalcemia Type 1 is a rare familial genetic form of hypoparathyroidism. Autosomal Dominant Hypocalcemia (ADH) Type 1 is typically passed down from affected parents to their children.
This is a Phase 2b open label, dose finding study to evaluate the safety and tolerability of CLTX-305 (encaleret) in Autosomal Dominant Hypocalcemia (ADH) Type 1 as well as the effects of CLTX-305 (encaleret) on blood calcium concentration.
The estimated duration of this study is 41 months. This study plans to evaluate multiple doses of the investigational drug CLTX-305 (encaleret), in addition to safety and efficacy. CLTX-305 is administered orally.
The study is divided into 3 Periods followed by a Long-Term Extension (LTE):
Periods 1: Up to 8 study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.
Period 2: Participants from Period 1, and up to 10 new study participants will be admitted to the NIH Clinical Center for 7 days, where they will be administered different doses of CLTX-305 (encaleret) for up to 5 days.
Period 3: 24 weeks during which eligible study participants who completed Period 2 will take CLTX-305 (encaleret) at home.
LTE: Up to 25 months during which eligible study participants who completed Period 3 will take CLTX-305 (encaleret) at home.
Study participants may:
- Participate in Period 1
- Participate in Period 2
- Participate in both Period 1 and Period 2
- Participate in Period 3 after completing Period 2
- Participate in LTE after completing Period 3
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Maryland
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Bethesda, Maryland, United States, 20892
- National Institute Of Health
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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 kg/m2
- 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 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 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 ng/mL
- Participants with hemoglobin (Hgb) < 13 g/dL for men and < 12 g/dL for women
- Estimated glomerular filtration rate (eGFR) < 25 mL/minute/1.73 m2 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1: Ascending + Steady-State Dose
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. |
Tablets administered orally
Other Names:
|
Experimental: Cohort 2: Steady-State Dose
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. |
Tablets administered orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Number of Participants with Adverse Events (AEs)
Time Frame: Up to 3 years
|
Up to 3 years
|
Change From Baseline in Albumin-Corrected Blood Calcium Concentrations (cCa)
Time Frame: Up to 25 weeks
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Up to 25 weeks
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Rate of Urinary Calcium Excretion
Time Frame: Predose, Up to 24 hours postdose
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Predose, Up to 24 hours postdose
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Change From Baseline in Intact Parathyroid Hormone (iPTH) Concentration in Blood
Time Frame: Predose, Up to 24 hours postdose
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Predose, Up to 24 hours postdose
|
Area Under the Concentration-Time Curve Etrapolated to infinity (AUC0-inf)
Time Frame: Predose, Up to 24 hours postdose
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Predose, Up to 24 hours postdose
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Maximum Plasma Concentration (Cmax)
Time Frame: Predose, Up to 24 hours postdose
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Predose, Up to 24 hours postdose
|
Time to Maximum Plasma Concentration (Tmax)
Time Frame: Predose, Up to 24 hours postdose
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Predose, Up to 24 hours postdose
|
Change From Baseline in Blood Calcium Concentration (cCa)
Time Frame: Up to 3 years
|
Up to 3 years
|
Urinary Calcium Clearance as Assessed by Fractional Excretion
Time Frame: Up to 3 years
|
Up to 3 years
|
Urinary Calcium Clearance as Assessed by 24-Hour Total Excretion
Time Frame: Up to 3 years
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Up to 3 years
|
Renal Function as Assessed by Estimated Glomerular Filtration Rate (eGFR)
Time Frame: Up to 3 years
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Up to 3 years
|
Serum levels of 1,25-(OH)2 Vitamin D
Time Frame: Up to 3 years
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Up to 3 years
|
Magnesium, Phosphate, Creatinine Levels as Assessed by Blood Sample Examinations
Time Frame: Up to 3 years
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Up to 3 years
|
PH, Magnesium, Phosphate, Sodium, Potassium, Creatinine, cyclic adenosine monophosphate (cAMP), Citrate Levels as Assessed by Urine Sample Examinations
Time Frame: Up to 3 years
|
Up to 3 years
|
Bone Resorption Markers as Assessed by Collagen Cross-Linked C-Telopeptide (CTx)
Time Frame: Up to 3 years
|
Up to 3 years
|
Bone Formation Markers as Assessed by Blood Procollagen Type 1 N-Propeptide (P1NP)
Time Frame: Up to 3 years
|
Up to 3 years
|
Collaborators and Investigators
Investigators
- Study Director: Calcilytix Medical Director, Calcilytix Therapeutics, Inc., a BridgeBio company
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CLTX-305-201
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Clinical Trials on Encaleret
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