A phase 1/2 study of SLN124 in patients with Polycythemia Vera

Phase 1

Recruiting

• Conditions: Polycythemia Vera; MedDRA version: 21.1Level: LLTClassification code: 10036061Term: Polycythemia vera Class: 10029104; Therapeutic area: Diseases [C] - Neoplasms [C04]

• Registration Number: CTIS2023-503544-13-00
• Lead Sponsor: Silence Therapeutics PLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-28
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Male and female patients aged 18 years or older, Patients who are not receiving cytoreductive therapy must have been discontinued from any prior cytoreductive therapy for at least 24 weeks before dosing and have recovered from any adverse events due to cytoreductive therapy., Patients receiving cytoreductive therapy with hydroxyurea, interferon, busulfan or ruxolitinib must have received a stable dose of cytoreductive therapy for at least 12 weeks before dosing with no planned change in cytoreductive dose., Patients must have had a dermatological examination within 6 months prior to screening., Must have an Eastern Cooperative Oncology Group score of 0, 1, or 2, Must be able and willing to comply with all protocol requirements., A confirmed diagnosis of PV according to the revised 2016 World Health Organization criteria: 1. Hb/Hct level above 16.5 g/dL/49% in men and 16 g/dL/48% in women or red cell mass > 25% above mean normal predicted value 2. Consistent bone marrow morphology 3. Presence of a JAK2V617F or JAK2 exon 12 mutation 4. Subnormal serum erythropoietin (Epo) level, Willing and able to provide written informed consent before any screening procedures and in accordance with national, local, and institutional guidelines, Prior to screening patients must have had = 3 phlebotomies in the last 6 months or 5 or more phlebotomies in the last 12 months, with documented raised hct and/or documented presentation of symptoms of PV, Records of phlebotomies and associated Hct performed at least 6 months or, if available, for up to 12 months, prior to screening and any of the following associated data (soluble transferrin receptor 1 [sTfR1], ferritin or transferrin saturation [TSAT], if available), Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at pre-dose on Day 1, Must agree to adhere to appropriate contraception requirements, as follows: a. Female patients of childbearing potential (who are heterosexually active) must agree to use one highly effective method of contraception, from the beginning of the screening period until 3 months after the last administration of study drug. b.Male patients must use a male condom (with or without spermicide) if sexually active with a WOCBP from the beginning of the screening period until 3 months after the last administration of study drug., Women of childbearing potential must agree to not donate ova, from the beginning of the screening period until 3 months after the last administration of study drug., Male patients must agree to not donate sperm from the beginning of the screening period until 3 months after the last administration of study drug.

Exclusion Criteria

Drug intolerance: a. History of intolerance to oligonucleotides, or GalNAc, or any component of SLN124. b. History of intolerance to s.c. injections, Co-morbidity: a. Any serious medical or surgical condition, laboratory abnormality, or active psychiatric disorder that, in the opinion of the Investigator, places the patient at significant or unacceptable risk if he/she were to participate in the study. b. Any known underlying disease that, in the opinion of the Investigator, might confound the ability to interpret data from the study. c. Infection requiring hospitalization or intravenous antimicrobial therapy, or opportunistic infection within 12 weeks prior to the start of dosing; d. Any infection requiring systemic antimicrobial therapy within 4 weeks prior to first dose. Prophylactic antibiotics are allowed. e. History of malignancies. Exceptions are (resolved local basal cell carcinoma [BCC] and non-melanoma skin tumors that have been resolved no less than 6 months from screening, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological finding of prostate cancer [T1a or T1b using Tumor, Node, Metastasis staging classification system] f.Significant renal impairment, defined as estimated glomerular filtration rate (using the Chronic Kidney Disease Epidemiology Collaboration equation) < 45 mL/min/1.73m2 at screening. g. History and/or clinical evidence of cirrhosis. h. Active infectious hepatitis A, B, or C virus. i. Known history or clinical evidence of alcohol and/or drug misuse within 2 years prior to screening. j. Clinically significant or symptomatic cardiac disease including cardiac arrhythmias. k. Clinically significant pulmonary disease., Biochemical and hematological parameters: a. Biochemical evidence of significant liver disease during screening, defined as alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5 × upper limit of normal (ULN); total bilirubin to = ULN; prothrombin time or International Normalized Ratio (INR) = ULN (Isolated INR = 1.3 is acceptable in the absence of other changes in liver function). b. Hematological parameters at screening as follows: platelets > 1,000,000/?L; or white blood cell (WBC) count >25,000/?L; or peripheral blasts > 1%., Pregnancy and reproduction: a. Femal patients who: are pregnant, or plan to be pregnant during the study, or are lactating, Clinically significant thrombosis (e.g., deep vein thrombosis or splenic vein thrombosis) within 12 weeks prior to screening, History of major bleeding events and/or a requirement for blood transfusion therapy owing to bleeding in the last 6 months prior to screening, Meets the criteria for post-PV myelofibrosis as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment [Gotlib et al, 2013]., Known primary or secondary immunodeficiency., Any major invasive surgical procedure requiring general anesthesia within 4 weeks prior to screening or planned elective surgery during the study., Any investigational drug less than 6 weeks prior to the first dose of study drug or not recovered from effects of prior administration of any investigational agent, Any investigational or marketed product using GalNAc targeting less than 48 weeks prior to administration of any investigational agent

Study & Design

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