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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: ITU512; Drug: Placebo

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).

• Study Type: Interventional
• Enrollment (Estimated): 161
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama Birmingham
      • Contact: Emily Burke; Phone Number: 205-975-4020; Email: eduke@uabmc.edu
      • Principal Investigator: Julie Kanter-Washko
  • Florida
    • Miami, Florida, United States, 33126
      • Completed
      • Quotient Sciences Sea View
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Boston Childrens Hospital
      • Principal Investigator: Matthew M Heeney
      • Contact: Nadia Tarhini; Phone Number: 617-355-4278; Email: nadia.tarhini@childrens.harvard.edu
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Lifespan
      • Contact: Asher Dillman; Phone Number: 401-444-5328; Email: adillmann@brownhealth.org
      • Principal Investigator: Patrick Mc Gann
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • UT Health Science Center
      • Principal Investigator: Modupe Idowu
      • Contact: Eyuel Baherey; Email: Eyuel.L.Baherey@uth.tmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1A; Part 1A in healthy participants	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.
Experimental: Part 1B; Part 1B in healthy participants	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.
Experimental: Part 1C; Part 1C in healthy participants	Drug: ITU512; ITU512 is an investigational, oral, low molecular weight (LMW) compound.
Experimental: Part 2A; Part 2A in patients with sickle cell disease	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.
Experimental: Part 2B; Part 2B in patients with sickle cell disease	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.
Experimental: Part 2C; Optional extension in patients with sickle cell disease	Drug: ITU512; ITU512 is an investigational, oral, low molecular weight (LMW) compound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	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.	Up to 5 months
Part 2A, Part 2B: Dose interruptions and reductions	Number of participants with dose interruptions or reductions of ITU512	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	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	Month 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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.	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 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	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	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	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	From pre-dose up to 144 hours post-dose
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	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	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	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	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	Up to 4 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): February 19, 2030

Study Registration Dates

• First Submitted: July 16, 2024
• First Submitted That Met QC Criteria: August 6, 2024
• First Posted (Actual): August 9, 2024

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Sickle cell disease; Small molecule; ITU512; Low molecular weight
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: CITU512A12101; 2024-515696-35-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No