A Phase I/II Study of ITU512 in Healthy Participants and Patients With Sickle Cell Disease
NCT Number: NCT06546670
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Sickle Cell Disease
Interventions: DRUG: ITU512|DRUG: Placebo
Sponsor: Novartis Pharmaceuticals
Sex: ALL
Age: CHILD, ADULT
Enrollment: 161
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: DOUBLE (PARTICIPANT, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-08-15
Completion Date: 2029-04-03
Locations: Quotient Sciences Sea View, Miami, Florida, 33126, United States

Summary:
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).

Primary Outcome Measures: 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 2: 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 2: Dose interruptions and reductions, Number of participants with dose interruptions or reductions of ITU512, Up to 4 months|Part 2: 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 2: HbF% evaluated from central laboratory assessments at Month 4, Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by high-performance liquid chromatography (HPLC) assay, Month 4
Secondary Outcome Measures: 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 2: 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 or 6 hours post-dose on Day 1 at Month 1 and Month 2|Part 2: 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 6 hours post-dose on Day 1 at Month 1|Part 2: Fetal hemoglobin (HbF)%, Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by HPLC assay, Up to 4 months|Part 2: 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 2: 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|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