A study to test the safety and effects of IMG-7289 in patients with essential thrombocythemia

Phase 1

• Conditions: Patients with essential thrombocythemia; MedDRA version: 21.0Level: LLTClassification code 10015494Term: Essential thrombocythemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-003659-13-DE
• Lead Sponsor: Imago BioSciences Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-16
• Last Update Posted: 18 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Patients must meet all of the applicable criteria to be eligible for enrollment in this study:
1. Age = 18 years.
2. Diagnosis of Essential Thrombocythemia per World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Arber et al., 2016).
3. Patients who have failed at least one standard therapy (failure is the equivalent of inadequate response or intolerance). European Leukemia Net (ELN) criteria for intolerance / resistance to hydroxyurea (Appendix 16.8) may be used in association with Investigator discretion. Ruxolitinib refractoriness or intolerance will be left to the discretion of the Investigator.
4. Requires treatment in order to lower platelet count based on patient age over 60 or history of thrombosis.
5. Platelet count > 450 k/µL (450 x 109/L) pre-dose Day 1.
6. Peripheral blast count < 1% pre-dose Day 1.
7. ANC = 0.5 x 109/L pre-dose Day 1.
8. Fibrosis Score < grade 2, as per a slightly modified version (Arber et al., 2016) of the European Consensus Criteria for Grading Myelofibrosis, (Thiele et al., 2005).
9. Life expectancy > 36 weeks.
10. Able to swallow capsules.
11. Amenable to bone marrow evaluations and peripheral blood sampling during the study.
12. Must have discontinued ET therapy at least 1 week (4 weeks for interferon) prior to study drug initiation.
13. Women of childbearing potential (WOCBP) and fertile men (see Section 6.1.) must agree to use an approved method of contraception from Screening until 14 days* after last IMG-7289 dose. Methods of contraception include: estrogen and progestogen combined hormonal contraception which inhibits ovulation; progestogen-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); bilateral tubal occlusion; vasectomized partner in a monogamous sexual relationship (vasectomy or tubal ligation at least six months prior to dosing); and, complete sexual abstinence (defined in Section 6.1). Males with a pregnant partner must agree to use a condom to avoid exposure to the developing child. Patients practicing abstinence must agree to use an approved method of contraception should they become sexually active during the study.
*The risk of embryofetal toxicity is fully mitigated by 28 days which is >10 half-lives of the drug at the doses used in this study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 21
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 39

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:
1. Hemoglobin < 10 g/dL prior to dosing on Day 1.
2. Transfusion dependency, defined as requiring 2 or more units of pack red blood cells per month for more than 3 months, or a hemoglobin level of =8g/dL in the preceding 8 weeks before the start of dosing.
3. Eastern Cooperative Oncology Group (ECOG) questionnaire score of 3 or greater at Screening.
4. History of splenectomy.
5. Has undergone major surgery =4 weeks prior to starting study drug or has not recovered from side effects of such surgery.
6. Unresolved treatment related toxicities from prior therapies (unless resolved to = Grade 1).
7. Uncontrolled active infection.
8. Known positive for HIV if not well-controlled (i.e., undetectable viral load) or infectious hepatitis, type A, B or C.
9. Current use of monoamine oxidase A and B inhibitors (MAOIs).
10. Evidence at the time of screening of increased risk of bleeding, including any of the following:
• Activated partial thromboplastin time (aPTT) > 1.3 x the upper limit of normal
• International normalized ratio (INR) >1.3 x the local upper limit of normal
• History of severe thrombocytopenia or platelet dysfunction unrelated to a myeloproliferative disorder or its treatment
• Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, haemophilia, Von Willebrand’s disorder, Disseminated Intravascular Coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency).
11. Evidence at the time of Screening of significant renal or hepatic insufficiency (unless due to haemolysis, or leukaemic infiltration) as defined by any of the following local lab parameters:
• Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) <40 mL/min or serum creatinine > 1.5 x the local upper limit of normal
• Aspartate transaminase (AST) or alanine aminotransferase (ALT) =2 x the local upper limit of normal
12. Current use of a prohibited medication (e.g., romiplostim) or expected to require any of these medications during treatment with the investigational drug.
13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IMG-7289 or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation.
14. History of any illness/impairment of gastrointestinal (GI) function that might interfere with drug absorption (e.g., chronic diarrhea), confound the study results or pose an additional risk to the patient by participation in the study; patients with gastric bypass surgery.
15. Use of an investigational agent within less than 14 days, or the equivalent of at least 7 half-lives of that agent, whichever is the longer, prior to the study Day 1.
16. Females who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study.
17. A concurrent second active and non-stable malignancy (patients with a concurrent second active but stable malignancy, such as nonmelanoma skin cancers, are eligible).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified