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Recruiting NCT06546670

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

Phase I / Phase II Interventional Sickle Cell Disease

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: ITU512, Placebo.
Who it may be relevant to
Registry conditions: Sickle Cell Disease. Basic parameters: 12 years — 55 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Turkey (Türkiye)
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

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

Overview

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).

Detailed description

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).

Interventions

  • Drug ITU512
    ITU512 is an investigational, oral, low molecular weight (LMW) compound.
  • Drug 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.

Primary outcome measures

  • Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs [Time frame: Up to approximately 60 days]
  • Part 1A, Part 1B , Part 1C: Dose discontinued due to AE [Time frame: Up to 30 days]
  • Part 2A, Part 2B: Incidence of AEs and SAEs [Time frame: Up to 5 months]
  • Part 2A, Part 2B: Dose interruptions and reductions [Time frame: Up to 4 months]
  • Part 2A, Part 2B: Dose intensity [Time frame: Up to 4 months]
  • Part 2B: Fetal hemoglobin (HbF)% [Time frame: Month 4]
Secondary outcome measures (12)
  • Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512 [Time frame: 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 [Time frame: 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 [Time frame: 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) [Time frame: 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 [Time frame: 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 [Time frame: From pre-dose up to 4 or 8 hours post-dose on Day 1 at Month 1]
  • Part 2A: Fetal hemoglobin (HbF)% [Time frame: Up to 4 months]
  • Part 2A, Part 2B: Change from baseline in total hemoglobin (Hb) [Time frame: Baseline, up to 4 months]
  • Part 1A, Part 1B, Part 2A, Part 2B: Change from baseline in Fridericia- corrected Holter QT interval (QTcF) [Time frame: 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 [Time frame: 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 [Time frame: From pre-dose up to 144 hours post-dose]
  • Part 1C: Maximum plasma concentration (Cmax) of ITU512 [Time frame: From pre-dose up to 144 hours post-dose]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation
Randomized
Model
Crossover
Masking
Double blind
Primary purpose
Treatment

Study locations

United States · 7 centers
  • 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 centers
  • Novartis Investigative Site — Ankara
  • Novartis Investigative Site — Adana

Identifiers

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

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗