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

Phase 2RecruitingNCT06546670

Novartis Pharmaceuticals161 enrolled

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).

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

161

Conditions

Sickle Cell Disease

Interventions

ITU512DRUG

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

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 12 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (10)

University of Alabama Birmingham

Birmingham, Alabama, United States

RECRUITING

Quotient Sciences Sea View

Miami, Florida, United States

COMPLETED

Outcomes

Primary Outcomes

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

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.

Time frame: Up to approximately 60 days

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

Number of participants with dose discontinuation due to AEs

Time frame: Up to 30 days

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

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.

Time frame: Up to 5 months

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

Number of participants with dose interruptions or reductions of ITU512

Time frame: Up to 4 months

Part 2A, Part 2B: Dose intensity

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

Time frame: Up to 4 months

Part 2B: Fetal hemoglobin (HbF)%

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

Time frame: Month 4

Secondary Outcomes

Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512

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

Central Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682 novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Boston Childrens Hospital

Boston, Massachusetts, United States

Levine Cancer Insitute Carolinas Healthcare System

Charlotte, North Carolina, United States

RECRUITING

East Carolina University

Greenville, North Carolina, United States

RECRUITING

Childrens Hospital Of Philadelphia

Philadelphia, Pennsylvania, United States

RECRUITING

Lifespan

Providence, Rhode Island, United States

RECRUITING

UT Health Science Center

Houston, Texas, United States

RECRUITING

Novartis Investigative Site

Ankara, Sihhiye-Altindag, Turkey (Türkiye)

RECRUITING

Novartis Investigative Site

Adana, Yuregir, Turkey (Türkiye)

RECRUITING

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

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

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

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

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)

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.

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

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

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

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

Time frame: From pre-dose up to 4 or 8 hours post-dose on Day 1 at Month 1

Part 2A: Fetal hemoglobin (HbF)%

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

Time frame: Up to 4 months

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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