A Phase 2 Study of KRT-232 in Myelofibrosis
Research type
Research Study
Full title
An Open-Label, Phase 2a/2b Study of KRT-232 in Subjects With Primary Myelofibrosis (PMF), Post–Polycythemia Vera MF (Post–PV-MF), Or Post–Essential Thrombocythemia MF (Post– ET-MF) Who Have Failed Prior Treatment with a JAK inhibitor.
IRAS ID
250788
Contact name
Donal McLornan
Contact email
Sponsor organisation
Kartos Therapeutics, Inc.
Eudract number
2018-001671-21
Clinicaltrials.gov Identifier
IND Number, 119156
Duration of Study in the UK
4 years, 4 months, 1 days
Research summary
Myelofibrosis (MF) is a rare but serious bone marrow disorder which disrupts the body’s ability to produce blood cells. It is characterised by the build-up of scar tissue (or ‘fibrosis’) in the bone marrow and often, an enlarged spleen. Until recently, there was no approved medical therapy for MF. Bone marrow transplant is the only treatment that can cure a patient. However, this is accompanied by high morbidity and mortality.
Ruxolitinib is an approved drug (in the US and EU) for the treatment of some kinds of MF, including Primary MF, post-Polycythemia Vera MF and Post-Essential Thrombocythemia MF. Ruxolitinib treatment results in spleen volume reduction in approximately 42 % of patients and helps improve general symptoms of the disease in approximately 46% of patients. However, it does not appear to have any impact on bone marrow fibrosis and MF symptoms relapse within 1 month of discontinuation. The poor prognosis for patients who fail to respond (or have sub-optimal response) to ruxolitinib represents an unmet need to treat and manage MF in the affected patient population.
The primary objective of this study is to investigate the effect of a small molecule agent (KRT-232) that is capable of binding to the MDM2 protein, inducing the activity of p53 - a critical tumour suppressor. P53 activity is usually inhibited by MDM2.
This study will be divided in two parts. Part A will enrol up to 90 participants who will be randomly assigned to 1 of 3 treatment groups with different doses and/or treatment schedules. Part B will recruit up to 100 participants who will be treated at the recommended dose and schedule determined from part A. Participants will be treated until disease progression or lack of tolerability.
Participants will undergo blood and urine tests, electrocardiograms, and imaging to monitor their disease.
REC name
London - Hampstead Research Ethics Committee
REC reference
18/LO/1605
Date of REC Opinion
3 Oct 2018
REC opinion
Further Information Favourable Opinion