A Phase I/II Study of ITU512 in Healthy Participants and Patients With Sickle Cell Disease

Официальное название

A Phase I/II Clinical Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ITU512 in Healthy Participants and Patients With Sickle Cell Disease

Обзор

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary food effect of ITU512 as well as the fetal hemoglobin (HbF)-inducing capacity of ITU512. This will be the first evaluation of the potential therapeutic effect of ITU512 in healthy participants and patients with sickle cell disease (SCD).

Подробное описание

This is a global, randomized, Phase I/II study to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary food effect of single-agent ITU512 in adult healthy participants, and safety, tolerability, PK, PD, and efficacy of ITU512 in adolescent and adult patients with sickle cell disease (SCD). The study consists of a first-in-human Phase I study (Part 1) in healthy participants, and a Phase II study (Part 2) in patients with SCD.

Part 1 will comprise of Part 1A, Part 1B, and Part 1C. Part 2 will include Part 2A and 2B and may also include an extension part (Part 2C).

Вмешательства

• Препарат ITU512
  ITU512 is an investigational, oral, low molecular weight (LMW) compound.
• Препарат Placebo
  An inactive substance that looks like and is given the same way as ITU512. The effect(s) of ITU512 will be evaluated against the placebo. Placebos are designed as a control and to have no real effect.

Первичные конечные точки

• Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs [Срок оценки: Up to approximately 60 days]
• Part 1A, Part 1B , Part 1C: Dose discontinued due to AE [Срок оценки: Up to 30 days]
• Part 2A, Part 2B: Incidence of AEs and SAEs [Срок оценки: Up to 5 months]
• Part 2A, Part 2B: Dose interruptions and reductions [Срок оценки: Up to 4 months]
• Part 2A, Part 2B: Dose intensity [Срок оценки: Up to 4 months]
• Part 2B: Fetal hemoglobin (HbF)% [Срок оценки: Month 4]

Вторичные конечные точки (12)

• Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512 [Срок оценки: From pre-dose up to 144 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B)]
• Part 1A, Part 1B: Maximum plasma concentration (Cmax) of ITU512 [Срок оценки: From pre-dose up to 144 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B)]
• Part 1A, Part 1B: Time to maximum plasma concentration (Tmax) of ITU512 [Срок оценки: From pre-dose up to 144 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B)]
• Part 1A, Part 1B: Renal clearance (CLr) [Срок оценки: From pre-dose up to 48 hours post-dose on Day 1 (Part 1A) and from pre-dose up to 24 hours post-dose on Day 1 and Day 10 (Part 1B)]
• Part 2A, Part 2B: Plasma concentrations of ITU512 [Срок оценки: From pre-dose up to 4, 6 or 8 hours post-dose on Day 1 at Month 1 and Month 2]
• Part 2A, Part 2B: Urine concentrations of ITU512 [Срок оценки: From pre-dose up to 4 or 8 hours post-dose on Day 1 at Month 1]
• Part 2A: Fetal hemoglobin (HbF)% [Срок оценки: Up to 4 months]
• Part 2A, Part 2B: Change from baseline in total hemoglobin (Hb) [Срок оценки: Baseline, up to 4 months]
• Part 1A, Part 1B, Part 2A, Part 2B: Change from baseline in Fridericia- corrected Holter QT interval (QTcF) [Срок оценки: Up to 4 months]
• Part 1C: Area under the plasma concentration-time curve from time 0 up to the time of the last quantifiable concentration (AUClast) of ITU512 [Срок оценки: From pre-dose up to 144 hours post-dose]
• Part 1C: Area under the plasma concentration-time curve from time 0 up to infinity (AUCinf) of ITU512 [Срок оценки: From pre-dose up to 144 hours post-dose]
• Part 1C: Maximum plasma concentration (Cmax) of ITU512 [Срок оценки: From pre-dose up to 144 hours post-dose]

Критерии участия

Критерии включения

Part 1 (Healthy participants)

• Healthy male participants and female participants of non-childbearing potential between 18-55 years of age
• In good health as determined by the investigator's assessment of medical history, physical examination, vital signs, ECG, and laboratory tests
• Participants must weigh at least 50 kg at screening and first baseline (admission) and must have a body mass index (BMI) within the range of 18.0-32.0 kg/m2 inclusive.

Part 2 (Sickle Cell Disease)

\- Male and female participants with a diagnosis of sickle cell disease

Критерии исключения

Part 1 (Healthy participants)

• QTcF ≥ 450 msec (as a mean value of triplicates)
• History of arrhythmias
• History of significant illness which has not resolved within two (2) weeks prior to initial dosing
• Women of child-bearing potential (WOCBP)

Part 2 (Sickle Cell Disease)

• Current use of hydroxyurea/hydroxycarbamide (HU/HC)
• QTcF ≥ 450 msec (as a mean value of triplicates)
• History of arrhythmias

Other protocol-defined inclusion/exclusion criteria may apply.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 7 центров

• University of Alabama Birmingham — Birmingham
• Quotient Sciences Sea View — Miami
• Boston Childrens Hospital — Boston
• East Carolina University — Greenville
• Childrens Hospital Of Philadelphia — Philadelphia
• Lifespan — Providence
• UT Health Science Center — Houston

Turkey (Türkiye) · 2 центра

• Novartis Investigative Site — Ankara
• Novartis Investigative Site — Adana

Идентификаторы

NCT: NCT06546670 · CITU512A12101 · 2024-515696-35-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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