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A Prospective, Open Label Phase I/II Study to Assess the Safety and Efficacy of Cycles of Intravenously Infused Doses of OPN-305 in Second-line Lower (Low and intermediate-1) Risk Myelodysplastic Syndrome (MDS)
OPN-305 is a monoclonal antibody; that means it is an antibody that is made in a laboratory in larger amounts than naturally occurring antibody. An antibody is a protein produced in our bodies that sticks to things that come into our bodies such as a virus in order to help remove them or stop them from causing harm. OPN-305 sticks onto and blocks the action of another protein called the TLR2 receptor. This is a two-part study. Part 1 researched the best dose of the study drug OPN-305 in the treatment of participants with low or intermediate-1 risk MDS and how often it should be given. Part 1 has already been completed. In Part 2 of this study, its purpose is to establish if the dose found in Part 1 can help to control low and/or intermediate-1 risk MDS when given alone or with azacitidine. Participants will be given the OPN-305 every 4 weeks at the hospital. At these visits, how the participants are responding to the study drug given at the previous visit will be checked. The safety of this study drug and how well it works was studied in Part 1 and will also be studied in Part 2.
Primary Objective: The primary objective of the study is to establish dose and dose frequency based on toxicity and bone marrow receptor occupancy of OPN-305 in low and intermediate -1 (Lower) risk MDS. The dose-confirming part of the study will provide the dose for the dose expansion part. The primary objective for dose and dose frequency will be based on the following: *Receptor occupancy at 8 weeks in bone marrow and peripheral blood. *Tolerability of OPN-305 as monotherapy or in combination with azacitidine. Secondary Objectives: Multiple secondary objectives are included in this study for efficacy, safety, pharmacodynamic and pharmacokinetic parameters. These secondary objectives are as follows: Efficacy: * To assess the effect of OPN-305 alone or in combination with azacitidine on: * Hematological response based on IWG 06 criteria (Cheson 2006), * Transfusion independence. * Lack of progression to high risk MDS or AML. Safety: Safety secondary objectives are: * To confirm that there are no unexpected (clinically meaningful) elevations of cytokine levels in serum (TNFá, IL-1â, IL-6, IL-10, IL-12,IL-18, IL-23 and IFN-ã) following cycles of intravenously infused OPN-305 in patients with low and intermediate-1 risk myelodysplastic syndrome. * To determine the immunogenicity (anti-drug antibodies and neutralizing antibodies) of OPN-305 after multiple doses of intravenously infused OPN-305 in patients with low and intermediate-1 risk myelodysplastic syndrome. * To assess whether the use of OPN-305 is associated with an increased risk of infection (particularly with opportunist organisms). Pharmacodynamic: Pharmacodynamic parameters are included in order: * To evaluate the effect of OPN-305 on pharmacodynamic parameters of receptor occupancy in: * Peripheral monocytes. * Bone marrow cells. Pharmacokinetic: Secondary objectives for pharmacokinetics are: * To determine the pharmacokinetic profile of intravenously infused OPN-305 in patients with low and intermediate-1 risk myelodysplastic syndrome. Exploratory Objectives: Based on the data from the study the exploratory objectives will be: * To correlate clinical response with known cytogenetical observations. * To explore quality of life outcomes using the MDASI - AML/MDS questionnaire.