A Phase I/II Study of ITU512 in Healthy Participants and Patients With Sickle Cell Disease
- Registration Number
- NCT06546670
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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).
- 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 may include an extension part.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 138
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
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part 1A Placebo Part 1A in healthy participants Part 1B ITU512 Part 1B in healthy participants Part 1B Placebo Part 1B in healthy participants Part 1C ITU512 Part 1C in healthy participants Part 2 ITU512 Part 2 in patients with sickle cell disease Part 2 Placebo Part 2 in patients with sickle cell disease Part 1A ITU512 Part 1A in healthy participants
- Primary Outcome Measures
Name Time Method Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs 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.
Part 1A, Part 1B , Part 1C: Dose discontinued due to AE Up to 30 days Number of participants with dose discontinuation due to AEs
Part 2: Incidence of AEs and SAEs 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.
Part 2: Dose interruptions and reductions Up to 4 months Number of participants with dose interruptions or reductions of ITU512
Part 2: Dose intensity Up to 4 months Dose intensity of ITU512 is computed as the ratio of actual cumulative dose received and actual duration of exposure
Part 2: HbF% evaluated from central laboratory assessments at Month 4 Month 4 Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by high-performance liquid chromatography (HPLC) assay
- Secondary Outcome Measures
Name Time Method Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512 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
Part 1A, Part 1B: Maximum plasma concentration (Cmax) of ITU512 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
Part 1A, Part 1B: Time to maximum plasma concentration (Tmax) of ITU512 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
Part 1A, Part 1B: Renal clearance (CLr) 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.
Part 2: Plasma concentrations of ITU512 From pre-dose up to 4 or 6 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
Part 2: Urine concentrations of ITU512 From pre-dose up to 4 or 6 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
Part 2: Fetal hemoglobin (HbF)% Up to 4 months Assessment of fetal hemoglobin expression by measuring fetal hemoglobin (HbF)% by HPLC assay
Part 2: Change from baseline in total hemoglobin (Hb) Baseline, up to 4 months Change from baseline in total hemoglobin (Hb) over time measured in blood samples
Part 1A, Part 1B, Part 2: Change from baseline in Fridericia-corrected Holter QT interval (QTcF) 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
Part 1C: Area under the plasma concentration-time curve from time 0 up to the time of the last quantifiable concentration (AUClast) of ITU512 From pre-dose up to 144 hours post-dose PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods
Part 1C: Area under the plasma concentration-time curve from time 0 up to infinity (AUCinf) of ITU512 From pre-dose up to 144 hours post-dose PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods
Part 1C: Maximum plasma concentration (Cmax) of ITU512 From pre-dose up to 144 hours post-dose PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods
Part 1C: Time to maximum plasma concentration (Tmax) of ITU512 From pre-dose up to 144 hours post-dose PK parameters calculated based on ITU512 plasma concentrations by non-compartmental methods
Trial Locations
- Locations (1)
Quotient Sciences Sea View
🇺🇸Miami, Florida, United States