Clinical trial NCT06546670: A Phase I/II Study of ITU512 in Healthy Participants and Patients With Sickle Cell Disease
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Sickle Cell Disease
Keywords: ITU512
Low molecular weight
Small molecule
Sickle cell disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2024-08-09
Enrollment: 161
Sex: ALL
Minimum age (years): 12
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1A, Part 1B, Part 1C: Incidence of AEs and SAEs
timeFrame: Up to approximately 60 days
measure: Part 1A, Part 1B , Part 1C: Dose discontinued due to AE
timeFrame: Up to 30 days
measure: Part 2: Incidence of AEs and SAEs
timeFrame: Up to 5 months
measure: Part 2: Dose interruptions and reductions
timeFrame: Up to 4 months
measure: Part 2: Dose intensity
timeFrame: Up to 4 months
measure: Part 2: HbF% evaluated from central laboratory assessments at Month 4
timeFrame: Month 4
Secondary outcomes:
measure: Part 1A, Part 1B: Area under the plasma concentration-time curve (AUC) of ITU512
timeFrame: 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)
measure: Part 1A, Part 1B: Maximum plasma concentration (Cmax) of ITU512
timeFrame: 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)
measure: Part 1A, Part 1B: Time to maximum plasma concentration (Tmax) of ITU512
timeFrame: 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)
measure: Part 1A, Part 1B: Renal clearance (CLr)
timeFrame: 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)
measure: Part 2: Plasma concentrations of ITU512
timeFrame: From pre-dose up to 4 or 6 hours post-dose on Day 1 at Month 1 and Month 2
measure: Part 2: Urine concentrations of ITU512
timeFrame: From pre-dose up to 4 or 6 hours post-dose on Day 1 at Month 1
measure: Part 2: Fetal hemoglobin (HbF)%
timeFrame: Up to 4 months
measure: Part 2: Change from baseline in total hemoglobin (Hb)
timeFrame: Baseline, up to 4 months
measure: Part 1A, Part 1B, Part 2: Change from baseline in Fridericia-corrected Holter QT interval (QTcF)
timeFrame: Up to 4 months
measure: Part 1C: Area under the plasma concentration-time curve from time 0 up to the time of the last quantifiable concentration (AUClast) of ITU512
timeFrame: From pre-dose up to 144 hours post-dose
measure: Part 1C: Area under the plasma concentration-time curve from time 0 up to infinity (AUCinf) of ITU512
timeFrame: From pre-dose up to 144 hours post-dose
measure: Part 1C: Maximum plasma concentration (Cmax) of ITU512
timeFrame: From pre-dose up to 144 hours post-dose
measure: Part 1C: Time to maximum plasma concentration (Tmax) of ITU512
timeFrame: From pre-dose up to 144 hours post-dose
Other outcomes:
Locations:
city: Miami
country: United States
facility: Quotient Sciences Sea View
state: Florida
Study officials:
References: