A Phase 2 Trial Investigating the Safety, Tolerability and Efficacy of EXT608 in Adults With Hypoparathyroidism

Официальное название

A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Trial Investigating the Safety, Tolerability and Efficacy of EXT608 in Adults With Hypoparathyroidism

Обзор

The goal of this clinical trial is to investigate the safety, tolerability and efficacy of EXT608 in adults with hypoparathyroidism.

Вмешательства

• Препарат EXT608
  Modified version of parathyroid hormone attached to vitamin D to extend half-life
• Другое Placebo
  Placebo for injection

Первичные конечные точки

• Assess the safety and tolerability of multiple subcutaneous (SC) escalating dose levels of EXT608 in participants with hypoparathyroidism by determining frequency and severity of treatment emergent adverse events and post-dose change in lab results [Срок оценки: From enrollment until the end of treatment at 12 weeks]

Вторичные конечные точки (4)

• Assess the pharmacokinetics (PK) of multiple SC doses of EXT608 given over 4 weeks in participants with hypoparathyroidism by determining Area Under the Curve (AUC) [Срок оценки: From enrollment until 4 weeks]
• Assess the pharmacokinetics (PK) of multiple SC doses of EXT608 given over 4 weeks in participants with hypoparathyroidism by determining drug half-life [Срок оценки: From enrollment until 4 weeks]
• Assess the clinical efficacy of multiple fixed SC doses of EXT608 given over 4 weeks (at week 4), and individualized dosing after an additional 8 weeks (at week 12) in participants with hypoparathyroidism by assessing serum calcium [Срок оценки: From enrollment until the end of treatment at 12 weeks]
• Assess the clinical efficacy of multiple fixed SC doses of EXT608 given over 4 weeks (at week 4), and individualized dosing after an additional 8 weeks (at week 12) in participants with hypoparathyroidism by assessing supplementation [Срок оценки: From enrollment until the end of treatment at 12 weeks]

Критерии участия

Критерии включения

• Ability to personally provide written, signed, and dated informed consent to participate in the study.
• An understanding, ability, and willingness to fully comply with study procedures and restrictions.
• Male or female between 18 and 65 years of age. Male participants with female partners of child bearing potential must agree to use barrier contraception, e.g., condoms plus spermicide, from administration of the study drug until at least 3 months after administration of the study drug. Abstinence from heterosexual intercourse from administration of study drug until at least 3 months after administration of study drug is acceptable if it is in accordance with the participant's lifestyle. Female participants should be either surgically sterile (had a bilateral tubal ligation, bilateral salpingectomy, bilateral oophorectomy, or hysterectomy), postmenopausal (defined as 12 months with no menses prior to screening and a serum follicle stimulating hormone in the postmenopausal range at screening), or, if of child bearing potential, must be non-lactating and willing to use a highly effective method of birth control for 30 days prior to administration of study drug and agree to continued use of this method until at least 3 months after administration of study drug.
• Participants have a history of hypoparathyroidism for 12 months at least, with PTH levels below the LLN with concomitant serum calcium < 9 mg/dL.
• Participants are treated with a daily dose > 750 mg elemental calcium if using > 0.25 µg/day calcitriol, or a daily dose > 1000 mg elemental calcium if not using calcitriol.
• Participants have normal blood levels of 25-hydroxyvitamin D (i.e. > 20 ng/dL or > 75 nmol/L) and not above 1.5 times the upper limit of normal.
• Participants have normal thyroid test results for 3 months at least while taking a stable dose of thyroid medication or no medication.
• Participants have a BMI < 35 kg/m2.
• Albumin-adjusted serum calcium level should be between the lower half and the middle of the normal range upon randomization into the study.

Критерии исключения

• Participants with hypoparathyroidism due to an activating mutation of the calcium sensing receptor, pseudohypoparathyroidism, any non-hypoparathyroidism disease that may affect calcium metabolism or phosphor-calcium homeostasis, or requiring parenteral calcium infusions.
• Unwillingness to use a diary deployed on a smartphone daily for recording vitamin D, active vitamin D, calcium, magnesium and study drug doses as well as periodic symptom reporting.
• Participants with a history of neoplasia (except thyroid cancer) with no sign of recurrence 5 years after diagnosis.
• Participants with a history of or active GI tract disease that may impact the absorption of calcium (e.g. malabsorption).
• Participants with a history of severe hypocalcemia leading to seizures or cardiac arrhythmias within 6 months prior to screening.
• Participants with chronic kidney disease (eGFR < 30 ml/min) or active nephrolithiasis (needing pain medication in the last 6 months).
• Participants taking the following medications within the respective exclusion period:

• Proton pump inhibitors (4 weeks)
• Bisphosphonates (3 months)
• Parathyroid hormone, PTH analogs (6 months)
• Thiazide diuretics (14 days)
• Calcitonin or calcinet hydrochloride (3 months)
• Participant has increased CV proarrhythmic potential:

• Participant has a QT interval with Fridericia's correction method (QTcF) >450 ms or PR outside the range of 120 to 220 ms, confirmed with one repeat testing, at the Screening Visit or Inpatient Check-in (Day -1) Visit.
• A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• The use of concomitant medications that prolong the QT/QTc interval.
• Chronic/severe cardiac disease including, but not limited to, cardiac insufficiency, unstable angina, arrhythmias, bradycardia (resting heart rate <60 beats/minute), or hypotension (systolic and diastolic blood pressures <100 and 60 mmHg, respectively).
• Any condition or disease that, in the opinion of the investigator, may interfere with a participant's participation or may confound the interpretation of safety or efficacy in the study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Аргентина · 1 центр

• Trial Site — Buenos Aires

Идентификаторы

NCT: NCT06988670 · EXT608-201 · R01FD007824 · R44DK138647

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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