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

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.

NCT Number	NCT07435636
Lead Sponsor	Clinical Hub for Interventional Research (CHOIR) Collaborators: Medical Research Future Fund, Australian National University, University of Auckland, New Zealand, Treebough Therapies, The University of New South Wales
Conditions	Clonal Cytopenia of Uncertain Significance, CCUS Clonal Cytopenia of Undetermined Significance, Clonal Hematopoiesis
Enrollment	80 participants
Start Date	2026-04-13
Primary Completion	2030-04-14 (estimated)
Study Completion	2030-10 (estimated)
Updated on ClinicalTrials.gov	2026-02-27