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NCT Number: NCT06546670

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

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).

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies

Age range

12 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Novartis Investigative Site, Ankara, Sihhiye-Altindag, Turkey (Türkiye)

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About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Key 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

Key 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.

Treatment and study plan

ITU512

Drug

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

Placebo

Drug

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 outcomes

  1. Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs

    Time frame: Up to approximately 60 days

    Number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.

  2. Part 1A, Part 1B , Part 1C: Dose discontinued due to AE

    Time frame: Up to 30 days

    Number of participants with dose discontinuation due to AEs

  3. Part 2A, Part 2B: Incidence of AEs and SAEs

    Time frame: Up to 5 months

    Number of participants with adverse events (AEs) and serious adverse events (SAEs), including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.

  4. Part 2A, Part 2B: Dose interruptions and reductions

    Time frame: Up to 4 months

    Number of participants with dose interruptions or reductions of ITU512

  5. Part 2A, Part 2B: Dose intensity

    Time frame: Up to 4 months

    Dose intensity of ITU512 is computed as the ratio of actual cumulative dose received and actual duration of exposure

  6. Part 2B: Fetal hemoglobin (HbF)%

    Time frame: Month 4

    Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by high-performance liquid chromatography (HPLC) assay

Secondary outcomes

  1. 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)

    Pharmacokinetic (PK) parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

  2. 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)

    PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

  3. 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)

    PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

  4. 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)

    PK parameters calculated based on ITU512 urine concentrations by non-compartmental methods. The renal clearance (CLr) may be determined based on AUC and amount of drug excreted into urine (Ae) available for the same time period.

  5. 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

    ITU512 concentration in plasma determined in non-placebo treated participants by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method

  6. 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

    ITU512 concentration in urine determined in non-placebo treated participants by a LC-MS/MS method

  7. Part 2A: Fetal hemoglobin (HbF)%

    Time frame: Up to 4 months

    Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by HPLC assay

  8. Part 2A, Part 2B: Change from baseline in total hemoglobin (Hb)

    Time frame: Baseline, up to 4 months

    Change from baseline in total hemoglobin (Hb) over time measured in blood samples

  9. Part 1A, Part 1B, Part 2A, Part 2B: Change from baseline in Fridericia- corrected Holter QT interval (QTcF)

    Time frame: Up to 4 months

    Real-time 12-lead safety ECGs will be locally collected and evaluated. Change from baseline in QTcF with respect to PK parameters and/or ITU512 concentrations will be assessed

  10. 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

    PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

  11. 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

    PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

  12. Part 1C: Maximum plasma concentration (Cmax) of ITU512

    Time frame: From pre-dose up to 144 hours post-dose

    PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

  13. Part 1C: Time to maximum plasma concentration (Tmax) of ITU512

    Time frame: From pre-dose up to 144 hours post-dose

    PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods

Study contacts

Contact information is provided by the study sponsor or research team.

Novartis Pharmaceuticals

CONTACT

[email protected]

1-888-669-6682

Novartis Pharmaceuticals

CONTACT

+41613241111

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2028
Study completion
2030
First posted
Aug 9, 2024
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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