Autosomal Dominant Hypocalcemia Type 1 (ADH1)
Conditions
Keywords
Autosomal dominant hypocalcemia type 1, ADH1, Encaleret
Brief summary
The overall objective of this study is to evaluate the pharmacokinetics (PK), efficacy, and safety of encaleret in pediatric participants from birth to 17 years of age with ADH1.
Interventions
DRUGEncaleret
Oral tablets, age-appropriate pediatric formulation (currently under development).
Sponsors
Calcilytix Therapeutics, Inc., a BridgeBio company
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Provide written informed consent (if legally permitted), or have written informed consent from a parent/legal guardian and provide assent (where required and as appropriate per local requirements) * Have a documented pathogenic or likely pathogenic activating variant, or variant of uncertain significance of the calcium-sensing receptor (CASR), associated with biochemical findings of hypoparathyroidism at screening or a documented history of hypoparathyroidism as manifested by hypocalcemia and intact parathyroid hormone (PTH) \<40 picogram per milliliter (pg/mL) (4.2 picomoles per liter \[pmol/L\]) * Have at least 1 symptom or sign of hypoparathyroidism at screening or a documented history of symptoms or signs of hypoparathyroidism * Be on ADH1 treatment for at least 6 months before screening for cohorts 1 to 3, or for at least 3 months before screening for cohort 4 Key
Exclusion criteria
* History of thyroid or parathyroid surgery * History of renal transplantation * History of cancer (except thyroid cancer, basal cell skin cancer, or squamous cell skin cancer), skeletal malignancies, bone metastases, irradiation (radiotherapy) to the skeleton, chemotherapy with alkylating agents, Paget disease, fibrous dysplasia, chronic osteomyelitis, bone infarcts, benign bone tumors with curettage and bone grafts, retinoblastoma, or Li-Fraumeni syndrome within 5 years before screening * Received any investigational medicinal product within 30 days or 5 half-lives before Day 1, whichever is longer, or is in follow-up for another interventional clinical study during screening * Treatment with a strong P-glycoprotein (P-gp) inhibitor within 300 days before screening for amiodarone or within 30 days before screening for any other strong P-gp inhibitor * Treatment with cardiac glycosides, or is being breastfed while the participant's nursing mother is treated with cardiac glycosides, within 30 days before screening * Presence or history of any disease or condition (eg, drug or alcohol dependence) that would affect the participant's safety, treatment compliance, or ability to complete the study, in the opinion of the investigator Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Period 1: Maximum Plasma Concentration (Cmax) of Encaleret and Metabolites M1, and M3 | 5 days |
| Period 1: Area Under the Plasma Concentration-time Curve (AUC) of Encaleret and Metabolites M1, and M3 | 5 days |
| Period 3: Number of Participants with Albumin-corrected Blood Calcium (cCa) and Urinary Calcium (UCa) Excretion Response | Week 25 |
Secondary
| Measure | Time frame |
|---|---|
| Period 1: Change from Baseline in Blood cCa | Baseline up to Day 5 |
| Period 1: Change from Baseline in Blood Intact Parathyroid Hormone (iPTH) Concentration | Baseline up to Day 5 |
| Period 1: Change from Baseline in Blood Phosphate Concentration | Baseline up to Day 5 |
| Period 1: Change from Baseline in Blood 1,25-(OH)2 Vitamin D Concentration | Baseline up to Day 5 |
| Period 1: Change from Baseline in Blood Magnesium Concentration | Baseline up to Day 5 |
| Period 1: Change from Baseline in 24-hour UCa in Toilet Trained Participants | Baseline up to Day 5 |
| Period 1: Change from Baseline in Spot Ratio of UCa/Urinary Creatinine (UCr) In Non-toilet Trained Participants | Baseline up to Day 5 |
| Period 3: Number of Participants with Blood iPTH Within the Reference Range | Week 25 (post-dose) |
| Period 3: Number of Participants with Blood Phosphate Within the Reference Range | Week 25 |
| Period 3: Number of Participants with Blood Magnesium Within the Reference Range | Week 25 |
| Period 3: Number of Participants with Blood 1,25-(OH)2 Vitamin D Within the Reference Range | Week 25 |
| Periods 1, 2, and 3: Change from Baseline in Short Form-10 Health Survey for Children (SF-10) in Participants Aged ≥6 Years | Baseline up to Week 25 |
| Periods 1, 2, and 3: Dose of Calcium Supplements and/or Active Vitamin D Analogs Used as Rescue Therapy | 25 weeks |
| Periods 1, 2, and 3: Dosing Frequency of Calcium Supplements and/or Active Vitamin D Analogs Used as Rescue Therapy | 25 weeks |
| Periods 1, 2, 3, and LTE: Number of Participants with Adverse Events (AEs) and Serious AEs (SAEs) | 145 weeks |
| LTE: Change from Baseline in Blood cCa | Baseline up to 145 weeks |
| LTE: Change from Baseline in Blood iPTH Concentration | Baseline up to 145 weeks |
| LTE: Change from Baseline in Blood Phosphate Concentration | Baseline up to 145 weeks |
| LTE: Change from Baseline in Blood 1,25-(OH)2 Vitamin D Concentration | Baseline up to 145 weeks |
| LTE: Change from Baseline in Blood Magnesium Concentration | Baseline up to 145 weeks |
| LTE: Change from Baseline in 24-hour UCa In Toilet Trained Participants | Baseline up to 145 weeks |
| LTE: Change from Baseline in Spot Ratio of UCa/UCr In Non-toilet Trained Participants | Baseline up to 145 weeks |
| LTE: Change from Baseline in SF-10 in Participants Aged ≥6 Years | Baseline up to 145 weeks |
Countries
United Kingdom, United States
Contacts
CONTACTMedical Information
STUDY_DIRECTORCalcilytix Medical Director
Calcilytix Therapeutics, Inc., a BridgeBio company
Outcome results
None listed