NCT07435636

Modulation of Stem Cell Differentiation in Individuals With High Risk Clonal Haematopoiesis

A Multi-centre, Double-blind, Placebo-controlled Randomised Phase II Trial to Evaluate the Effect of Low Dose Decitabine and Tetrahydrouridine in Individuals With High-risk Clonal Haematopoiesis

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Clinical Hub for Interventional Research (CHOIR) · Other Government
• Sex: All
• Age: 60 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

Clonal hematopoiesis (CH) is characterized by the overproduction of blood cells derived from a single hematopoietic stem and progenitor cell (HSPC) harboring certain somatic mutations. It is linked to serious outcomes, including cardiovascular disease, myeloid neoplasm (MN), and increased mortality. Clonal Cytopenia of Uncertain Significance (CCUS) is a CH subtype characterized by associated persistent cytopenia. It affects approximately 10 % of people over 70 and is the most advanced precursor state with the highest risk of progressing to MN. There is an unmet need to determine whether modifying CH can prevent adverse outcomes. Current blood cancer therapies are too toxic for precursor conditions like CH. MOSAIC is a randomized double-blind placebo-controlled trial that will test a novel low-dose oral epigenetic therapy-decitabine with tetrahydrouridine (Dec+THU) in CCUS. It has shown targeted, non-cytotoxic reversal of common CH mutations in preclinical and early-phase studies. The goal is to develop a safe and effective therapy in CCUS that restores normal blood cell production and prevents progression.

Conditions

• Clonal Cytopenia of Uncertain Significance
• CCUS Clonal Cytopenia of Undetermined Significance
• Clonal Hematopoiesis

Interventions

Type	Name	Description
DRUG	Oral Decitabine and Tetrahydrouridine	After randomization, participants will receive oral combination capsules containing decitabine (Dec) (2.5 mg) and tetrahydrouridine (THU) (125 mg) minitablets, or matched placebo. Trial medication will be dispensed on Day 1 of each cycle and taken once weekly (Days 1, 8, 15, 22) for 24 weeks. Dosing of Dec+THU will follow weight-based dosing at 0.2mg/kg and 10mg/kg respectively. This is a phase II, multicenter, double-blind, placebo-controlled randomized trial
DRUG	Matched Placebo (Capsules)	Placebo capsules will be administered on the same schedule and dosing frequency to the active drug

Timeline

• Start date: 2026-04-13
• Primary completion: 2030-04-14
• Completion: 2030-10-01
• First posted: 2026-02-27
• Last updated: 2026-02-27

Locations

3 sites across 1 country: Australia