A Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ALE1 in Healthy Adults and Adults With Hypophosphatasia in Order to Identify Suitable Doses of ALE1

Официальное название

A Randomised, Placebo Controlled, Double-Blind, Single-Ascending Dose And Multiple-Ascending Dose First-In-Human Study To Investigate The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Orally Administered ALE1 With Or Without Food In Healthy Adult Subjects And Adult Patients With Hypophosphatasia

Обзор

This is a phase 1/2a randomised, placebo controlled, double-blind study investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of ALE1 on healthy adult subjects and adult patients with Hypophosphatasia (HPP).

Вмешательства

• Препарат ALE1
  Specified dose on specified days
• Препарат Placebo
  Specified dose on specified days

Первичные конечные точки

• Evaluate the safety of ALE1 by assessing the number of treatment emergent adverse events (TEAEs) [Срок оценки: From baseline up to day 16]
• Evaluate safety of ALE1 by assessing the presence of clinically significant changes in participants haematology parameters post-dose [Срок оценки: From baseline up to day 16]
• Evaluate safety of ALE1 by assessing the presence of clinically significant changes in participants biochemistry parameters post-dose [Срок оценки: From baseline up to day 16]
• Evaluate safety of ALE1 by assessing changes in heart rhythms via electrocardiogram [Срок оценки: From baseline up to day 16]
• Evaluate safety of ALE 1 by assessing the presence of clinically significiant changes in participants vital signs [Срок оценки: From baseline up to day 16]

Вторичные конечные точки (10)

• Pharmacokinetic parameter: area under the plasma concentration versus time curve (AUC (D0 - INF)) [Срок оценки: From baseline up to day 16]
• Pharmacokinetic parameter: time at which maximum plasma concentration occurs (Tmax) [Срок оценки: From baseline up to day 16]
• Pharmacokinetic parameter: terminal elimination phase half-life (t(1/2)) [Срок оценки: From baseline up to day 16]
• Pharmacokinetic parameter: total clearance (CL/F) [Срок оценки: From baseline up to day 16]
• Pharmacokinetic parameter: volume of distribution (Vd/F) [Срок оценки: From baseline up to day 16]
• Change in pharmacodynamic biomarker levels in blood samples of ALE1 [Срок оценки: From baseline up to day 16]
• Dose proportionality of maximum observed plasma concentration (Cmax) Time at which maximum plasma concentration occurs (Tmax) [Срок оценки: From baseline up to day 16]
• Dose proportionality of area under the plasma concentration versus time curve (AUC (D0 - INF)) [Срок оценки: From baseline up to day 16]
• Effect of food on area under the plasma concentration versus time curve (AUC (D0 - INF)) [Срок оценки: From baseline up to 16 days post dose]
• Effect of food on maximum observed plasma concentration (Cmax) [Срок оценки: From baseline up to day 16]

Критерии участия

Key Inclusion Criteria Part 1:

• Participants are overtly healthy as determined by a medical evaluation
• No concurrent medical conditions or significant medical history, in the opinion of the investigator.

Key Inclusion Criteria Part 2:

1\. Documented ALPL gene variant

Key Exclusion Criteria Part 1:

1\. History of conditions affecting bone or mineral metabolism

Key Exclusion Criteria Part 2:

• Previous treatment with an enzyme replacement therapy (ERT) or any advanced therapeutic agent (e.g., gene therapy) for the treatment of hypophosphatasia (HPP) or any treatment for osteoporotic diseases
• Previous exposure to any medication or investigational agent potentially affecting bone structure, muscle volume, muscle strength, or muscle or nerve function
• Diagnosis of hyperparathyroidism
• Diagnosis of hypoparathyroidism, unless secondary to HPP
• New fracture within 12 weeks before first dosing

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Германия · 1 центр

• Universitätsklinikum Würzburg — Würzburg

Новая Зеландия · 1 центр

• New Zealand Clinical Research — Grafton

Великобритания · 1 центр

• Fortrea Clinical Research Unit — Leeds

Идентификаторы

NCT: NCT07179640 · ALE1-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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