A Phase 3 Randomized Clinical Trial to Investigate the Safety and Efficacy of Palopegteriparatide at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism

Официальное название

A Phase 3, Multicenter, Randomized, Open-Label Trial Investigating the Safety, Tolerability and Efficacy of Palopegteriparatide Administered Subcutaneously Daily at Doses Greater Than 30 μg/Day in Adult Participants With Hypoparathyroidism

Обзор

This trial has a treatment duration of 78 weeks and will include adult participants already on treatment with palopegteriparatide at doses at or greater than 30 mcg/day. All participants will receive subcutaneous palopegteriparatide during the trial and will be individually and progressively titrated to an optimal dose at pre-specified dose levels. The primary purpose of the trial is to provide additional evidence of treatment effect and safety of palopegteriparatide at doses greater than 30 mcg/day in adults with hypoparathyroidism. The trial will be conducted in the US.

Вмешательства

• Комбинированный продукт Palopegteriparatide Experimental Arm
  Palopegteriparatide is administered as separate SC injection in a prefilled, single-patient use pen. Treatment duration 78 weeks.
• Комбинированный продукт Palopegteriparatide Control Arm
  Palopegteriparatide is administered as separate SC injection in a prefilled, single-patient use pen. Treatment duration 78 weeks.

Первичные конечные точки

• Efficacy - Primary endpoint [Срок оценки: 26 weeks]

Критерии участия

Критерии включения

• Males and females, ≥18 years of age at the time of providing informed consent
• Participants with postsurgical chronic hypoparathyroidism (HP), or auto-immune, genetic, or idiopathic HP, for at least 26 weeks
• Receiving doses of palopegteriparatide at or above 30 µg/day

For individuals receiving 30 µg/day: evidence that dose is insufficient to keep serum calcium in the normal range, defined as:

Documented hypocalcemia within 12 weeks prior to Screening; and/or Standing dose of calcitriol ≥0.25 μg/day, and / or (elemental) calcium ≥1500 mg/day (e.g., calcium citrate, calcium carbonate etc.) for at least 4 weeks prior to Screening

For individuals receiving 33 µg/day or greater: no requirement for documented hypocalcemia or minimum doses of calcitriol or elemental calcium

• Confirmation of laboratory parameters (Central or Local) within 2 weeks of screening visit and prior to randomization:

25(OH) vitamin D levels of ≥ 20 ng/mL (≥49 nmol/L) and Magnesium level in the normal range, or just below the normal range i.e.: ≥1.3 mg/dL (≥0.53 mmol/L) and Albumin-adjusted or ionized sCa level in the normal range or just below the normal range

• Albumin-adjusted sCa 7.8 - 10.6 mg/dL (or 1.95 - 2.64 mmol/L)
• Ionized sCa 4.40 - 5.29 mg/dL (1.10 - 1.32 mmol/L)

5\. BMI 17- 40 kg/m2 at Screening

6\. If ≤25 years of age, radiological evidence of epiphyseal closure based on locally interpreted X-ray of non-dominant wrist and hand

7\. eGFR ≥30 mL/min/1.73 m2 during Screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula

Критерии исключения

• Impaired responsiveness to PTH (pseudohypoparathyroidism), which is characterized as PTH-resistance, with elevated PTH levels in the setting of hypocalcemia
• Any disease that might affect calcium metabolism or calcium-phosphate homeostasis or PTH levels other than HP
• Use of loop diuretics, phosphate binders (other than calcium supplements), digoxin, lithium, methotrexate, biotin >30 µg/day, or systemic corticosteroids (other than as replacement therapy)
• Use of thiazide diuretic within 4 weeks prior to the 24-hour urine collection scheduled to occur within 1 week prior to Visit 1
• Use of PTH-like drugs other than palopegteriparatide (whether commercially available or through participation in an investigational trial), including PTH(1-34), or other N-terminal fragments, analogs of PTH or PTH-related protein, or PTH1R biased agonists within 4 weeks prior to Screening
• Use of drugs known to influence calcium and bone metabolism within 12 weeks prior to Screening
• Use of denosumab or romosozumab within 2 years prior to Screening. Use of raloxifene within 4 weeks prior to Screening.
• Non-hypocalcemic seizure disorder with occurrence of a seizure within 26 weeks prior to Screening.
• Increased risk for osteosarcoma
• Women who are pregnant, intend to become pregnant, or are lactating
• Diagnosed drug or alcohol dependence within 3 years prior to Screening
• Chronic or severe cardiac disease within 26 weeks prior to Screening
• Cerebrovascular accident within 5 years prior to Screening.
• Within 26 weeks prior to Screening: acute colic due to nephrolithiasis, or acute gout
• Participation in any other interventional trial in which receipt of investigational drug or device other than palopegteriparatide occurred within 8 weeks (or within 5.5 times the half-life of the investigational drug) (whichever comes first) prior to Screening.
• Known allergy or sensitivity to PTH or any of the excipients \[metacresol, mannitol, succinic acid, NaOH/(HCl)\] of the investigational product

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

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• Ascendis Pharma Investigational Site — Reno
• Ascendis Pharma Investigational Site — New York
• Ascendis Pharma Investigational Site — Spokane Valley

Идентификаторы

NCT: NCT07081997 · ASND0052

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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