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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02363491
Recruitment Status : Recruiting
First Posted : February 16, 2015
Last Update Posted : April 9, 2018
M.D. Anderson Cancer Center
Information provided by (Responsible Party):
Opsona Therapeutics Ltd.

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 an additional 30 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 line Lower risk MDS).

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndrome Drug: OPN-305 Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : January 2015
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : April 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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 ]
  2. Tolerability of OPN-305 as monotherapy based on adverse events [ Time Frame: 16 weeks/32 weeks (if there is no AZA add-back) ]
  3. Tolerability of OPN-305 in combination with AZA based on adverse events [ Time Frame: 32 weeks ]

Secondary Outcome Measures :
  1. Hematological response based on IWG06 criteria, transfusion independence and lack of progression to high risk MDS or AML [ Time Frame: wk 36 ]
  2. 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 wk 4 ]
  3. Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies) [ Time Frame: day 1, wks 4, 8, 16, 24 and 32 ]
  4. Incidence of infections [ Time Frame: 36 weeks ]
  5. Pharmacokinetic profile of OPN-305 (Cmax, tmax, AUCinf, t1/2, CL, Vd) [ Time Frame: day 1, wks 4, 8, 12, 16, 20, 24, 28, 32 ]
  6. OPN-305 receptor occupancy in blood and bone marrow cells [ 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) ]
  7. Correlation of clinical response with cytogenic data eg expression, mutational to see if clinical response given by subset [ Time Frame: wk 36 ]
  8. Correlation of clinical response with QOL questionnaire feedback in terms of symptoms and severity through study completion [ Time Frame: wk 36 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Written informed consent
  • Age ≥ 18 years
  • Diagnosis of MDS (de novo or secondary) by bone marrow biopsy based on the World Health Organization (WHO) classification - Low and Intermediate-1 risk categories MDS using the IPSS (International Prognostic Scoring System)
  • Not responding or failed treatment on AZA or decitabine (note they are also eligible if additionally they have failed another ESA after at least 4 cycles)

    • Responders who cease responding
    • Never responded
  • Red Blood cell transfusion dependent (defined as ≥ 2 RBC units required in the 8 weeks prior to starting in the study).
  • Life expectancy ≥ 3 months
  • ECOG performance status Grade 0-2
  • Serum bilirubin levels ≤2 x ULN
  • Serum ALT and AST levels ≤2.5 x ULN
  • Creatinine clearance > 50 ml/min calculated by the Cockcroft-Gault formula
  • 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 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 biopsy of Intermediate-2 and High risk category MDS based on the WHO classification using the IPSS (International Prognostic Scoring System)
  • Patients with 5q del MDS unless failed on Revlimid (lenalidomide)
  • 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 or basal cell cancer of the skin) 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 patient 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 CNS disease
  • Less than 4 weeks since any therapy for MDS
  • Prior history of anaphylaxis with this product type
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02363491

Contact: Robert M Miller, FRCS, MBBS +44 203 2913032

United States, Florida
Research Site Recruiting
Tampa, Florida, United States, 33613
United States, New York
Research Site Recruiting
Bronx, New York, United States, 10467
Research Site Recruiting
New York, New York, United States, 10021
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Opsona Therapeutics Ltd.
M.D. Anderson Cancer Center
Principal Investigator: Guillermo Garcia Manero, MD M.D. Anderson Cancer Center

Responsible Party: Opsona Therapeutics Ltd. Identifier: NCT02363491     History of Changes
Other Study ID Numbers: OPN-305-106
First Posted: February 16, 2015    Key Record Dates
Last Update Posted: April 9, 2018
Last Verified: April 2018

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions