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

January 24, 2019 updated by: Opsona Therapeutics Ltd.

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 or Third-line Lower (Low and Intermediate-1) Risk Myelodysplastic Syndrome (MDS)

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).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
96

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33613
        • Research Site
    • New York
      • Bronx, New York, United States, 10467
        • Research Site
      • New York, New York, United States, 10021
        • Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.
  • Life expectancy ≥ 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status Grade 0-2
  • Serum bilirubin levels ≤2 x upper limits of normal (ULN)
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤2.5 x ULN
  • Del 5q patients who have failed or are not eligible for Revlimid
  • Creatinine clearance >30 ml/min calculated by the Cockcroft-Gault formula
  • Willingness to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations
  • Negative urine β-human chorionic gonadotropin (β-HCG) pregnancy test for fertile women at screening and confirmed by serum pregnancy test in the 48 hours prior to OPN-305 administration
  • If sexually active female, patient must be/have one of the following:
  • Post-menopausal defined as the absence of menses for at least one year (serum Follicle-stimulating hormone (FSH) ≥20IU/L can also be measured according to local practice),OR
  • Surgically sterile defined as a bilateral tubal ligation at least 6 months prior to administration of study drug, bilateral oophorectomy, or complete hysterectomy, OR
  • Using an effective means of contraception that is planned to continue for the duration of treatment and for a further 3 months.
  • If sexually active male, patient must: Agree to use an effective means of contraception (per site-specific guidelines) that is planned to continue until 6 months after the last dose of OPN-305.Agree not to donate sperm until 6 months after the last dose of OPN-305

Exclusion Criteria:

  • 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
    • Are not ESA ineligible as defined in inclusion criteria
  • 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
  • Lactating or pregnant woman

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: OPN-305
Drug: OPN-305
For the dose confirming part of the study, patients will receive a starting dose of 5 mg/kg OPN-305.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Time Frame: 8 weeks
8 weeks
Tolerability of OPN-305 as monotherapy based on adverse events
Time Frame: 16 weeks/32 weeks (if there is no AZA add-back)
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
Time Frame: 32 weeks
32 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Hematological response based on International Working Group (IWG) 2000/2006
Time Frame: week 36
week 36
Cytokine levels in serum (TNFα, IL-1β, IL-6, IL-10, IL-12, IL-18, IL-23 and IFN-γ)
Time Frame: day 1 and week 4
day 1 and week 4
Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies)
Time Frame: day 1, weeks 4, 8, 16, 24 and 32
day 1, weeks 4, 8, 16, 24 and 32
Incidence of infections
Time Frame: 36 weeks
36 weeks
Pharmacokinetic profile of OPN-305 (maximum concentration (Cmax))
Time Frame: day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32
day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32
Pharmacokinetic profile of OPN-305 (time at which Cmax is attained (tmax))
Time Frame: day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32
day 1, weeks 4, 8, 12, 16, 20, 24, 28, 32
OPN-305 receptor occupancy in peripheral monocytes, bone marrow cells and stroma
Time Frame: screening (bone marrow only), day 1 (blood only), wks 4 (blood only), 8, 12 (blood only), 16, 20 (blood only), 24 (blood only), 28 (blood only), 32 and 36 (blood only)
screening (bone marrow only), day 1 (blood only), wks 4 (blood only), 8, 12 (blood only), 16, 20 (blood only), 24 (blood only), 28 (blood only), 32 and 36 (blood only)
Correlation of clinical response with cytogenical observations
Time Frame: wk 36
wk 36
Quality of life MD Anderson Symptom Inventory (MDASI) - Acute Myeloid Leukemia (AML)/Myelodysplastic syndrome (MDS) questionnaire
Time Frame: wk 36

MDASI is MD Anderson symptom inventory. It has two scales

  1. Severity of symptoms scale 0-10 with 0 being not present and 10 being as bad as you can imagine
  2. How symptoms interfere with life scale 0-10 with 0 did not interfere and 10 interfere completely
wk 36

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Opsona Therapeutics Ltd.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
M.D. Anderson Cancer Center
Montefiore Medical Center
New York Presbyterian Hospital
H. Lee Moffitt Cancer Center and Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Guillermo Garcia Manero, MD, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 21, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 9, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 16, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 28, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 24, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • OPN-305-106

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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