Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants With Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Официальное название

A Phase 2/3, Multicenter, Single-Arm, Open-Label Study Evaluating the Pharmacokinetics, Efficacy, and Safety of Encaleret in Pediatric Participants With Autosomal Dominant Hypocalcemia Type 1 (ADH1)

Обзор

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.

Вмешательства

• Препарат Encaleret
  Oral tablets, age-appropriate pediatric formulation (currently under development).

Первичные конечные точки

• Period 1: Maximum Plasma Concentration (Cmax) of Encaleret and Metabolites M1, and M3 [Срок оценки: 5 days]
• Period 1: Area Under the Plasma Concentration-time Curve (AUC) of Encaleret and Metabolites M1, and M3 [Срок оценки: 5 days]
• Period 3: Number of Participants with Albumin-corrected Blood Calcium (cCa) and Urinary Calcium (UCa) Excretion Response [Срок оценки: Week 25]

Вторичные конечные точки (12)

• Period 1: Change from Baseline in Blood cCa [Срок оценки: Baseline up to Day 5]
• Period 1: Change from Baseline in Blood Intact Parathyroid Hormone (iPTH) Concentration [Срок оценки: Baseline up to Day 5]
• Period 1: Change from Baseline in Blood Phosphate Concentration [Срок оценки: Baseline up to Day 5]
• Period 1: Change from Baseline in Blood 1,25-(OH)2 Vitamin D Concentration [Срок оценки: Baseline up to Day 5]
• Period 1: Change from Baseline in Blood Magnesium Concentration [Срок оценки: Baseline up to Day 5]
• Period 1: Change from Baseline in 24-hour UCa in Toilet Trained Participants [Срок оценки: Baseline up to Day 5]
• Period 1: Change from Baseline in Spot Ratio of UCa/Urinary Creatinine (UCr) In Non-toilet Trained Participants [Срок оценки: Baseline up to Day 5]
• Period 3: Number of Participants with Blood iPTH Within the Reference Range [Срок оценки: Week 25 (post-dose)]
• Period 3: Number of Participants with Blood Phosphate Within the Reference Range [Срок оценки: Week 25]
• Period 3: Number of Participants with Blood Magnesium Within the Reference Range [Срок оценки: Week 25]
• Period 3: Number of Participants with Blood 1,25-(OH)2 Vitamin D Within the Reference Range [Срок оценки: 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 [Срок оценки: Baseline up to Week 25]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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/exclusion criteria apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• Yale University — New Haven
• Children's National Medical Center — Washington D.C.
• Nemours Children's Health — Jacksonville
• The Children's Hospital of Philadelphia — Philadelphia

Великобритания · 2 центра

• Royal London Hospital — London
• Royal Manchester Children's Hospital — Manchester

Идентификаторы

NCT: NCT07080385 · CLTX-305-303

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗