A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome

NCT02363491 | Completed Phase 1 DMC

• 1 other identifier: OPN-305-106
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 4

Brief Summary

The dose-confirming part of this study, comprising at least 10 patients is designed as a single center, prospective, single arm, open label in patients who have failed or are unresponsive to Azacitidine (AZA) or Decitabine (they may also have additionally failed an Erythropoiesis Stimulating Agent (ESA) followed by a dose expansion part with at least 44 patients; the objective of the whole study being to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of intravenously infused multiple doses of OPN-305 in low and intermediate-1 risk myelodysplastic syndrome (second and third line Lower risk MDS).

Conditions

Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (3)

• Establishment of the dose and dose frequency based on dose-limiting toxicity and bone marrow receptor occupancy of OPN-305 in low and intermediate -1 (Lower) risk MDS

  8 weeks

• Tolerability of OPN-305 as monotherapy based on adverse events

  16 weeks/32 weeks (if there is no AZA add-back)

• Tolerability of OPN-305 as monotherapy and in combination with AZA based on adverse events

  32 weeks

Secondary Outcomes (9)

• Hematological response based on International Working Group (IWG) 2000/2006

  week 36

• Cytokine levels in serum (TNFα, IL-1β, IL-6, IL-10, IL-12, IL-18, IL-23 and IFN-γ)

  day 1 and week 4

• Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies)

  day 1, weeks 4, 8, 16, 24 and 32

• Incidence of infections

  36 weeks

• Pharmacokinetic profile of OPN-305 (maximum concentration (Cmax))

  day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32

Study Arms (1)

OPN-305

EXPERIMENTAL

OPN-305

Drug: OPN-305

Interventions

OPN-305 DRUG

For the dose confirming part of the study, patients will receive a starting dose of 5 mg/kg OPN-305.

OPN-305

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Age ≥ 18 years
• Diagnosis of MDS (de novo or secondary) by bone marrow aspirate based on the World Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS using the IPSS (International Prognostic Scoring System)
• AZA/decitabine (this applies to standard of care and investigational drugs) failure (Dose confirming and Dose expansion parts):
• defined as discontinuation due to any of the following:
• Lack of response after at least 4 cycles
• Loss of response (patient must have received therapy for at least 4 cycles)
• Progressive disease
• Adverse events
• Note: Patients are eligible if additionally they have failed an ESA
• HMA Naïve group:
• Never received a hypomethylating agent for MDS
• Failed or ceased to respond to ESA(s)
• ESA ineligible; defined as endogenous serum erythropoietin level \> 200 U/L for subjects not previously treated with ESAs
• Red blood cell transfusion dependent defined as ≥ 2 Red blood cells (RBC) units required in the 8 weeks prior to starting in the study. In addition, there should be no 8 consecutive weeks without red blood cell transfusions in the 16 weeks prior to enrolment.

You may not qualify if:

• Diagnosis of MDS by bone marrow aspirate of Intermediate-2 and High risk category MDS based on the World Health Organization (WHO) classification using the IPSS (International Prognostic Scoring System)
• Patients with 5q deletion (del) MDS eligible for Revlimid (lenalidomide)
• Hypomethylating agent (HMA) Naïve group:
• Have received a hypomethylating agent for MDS
• Have not failed or ceased to respond to an ESA
• Prior history of acute leukemia or AML
• Unable/unwilling to undergo bone marrow sampling
• Prior history of bone marrow transplantation
• Prior malignancy (other than non-invasive malignancy including in situ cervical cancer, Bowen's disease, basal cell cancer of the skin and non-invasive or excised skin squamous cell carcinoma) unless treated with curative intent and without evidence of disease for 3 years before randomization
• Active viral or bacterial infections: this includes any infections that are being actively treated even if the signs and symptoms appear to have resolved. Courses of antibiotics or anti-viral treatment should be completed before the patients is enrolled
• Unstable angina, congestive heart failure \[NYHA (New York Heart Association) \>class II\], uncontrolled hypertension \[diastolic \> 100 mmHg\], uncontrolled cardiac arrhythmia, or recent (within 1 year) myocardial infarction, uncontrolled diabetes mellitus
• Clinical Evidence of Central Nervous System (CNS) disease
• Less than 4 weeks since any therapy for MDS
• Prior history of anaphylaxis to similar products
• History or presence of a medical condition or disease or substance abuse that in the investigator's assessment would place the patient at an unacceptable risk for study participation

Sponsors & Collaborators

• Opsona Therapeutics Ltd.: lead
• M.D. Anderson Cancer Center: collaborator
• Montefiore Medical Center: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• New York Presbyterian Hospital: collaborator

Study Sites (4)

Research Site

Tampa, Florida, 33613, United States

Location

Research Site

New York, New York, 10021, United States

Location

Research Site

The Bronx, New York, 10467, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

tomaralimab

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Guillermo Garcia Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2015
• First Posted: February 16, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: January 28, 2019

Record last verified: 2019-01

Locations

US (4)