Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02363491
Recruitment Status : Completed
First Posted : February 16, 2015
Last Update Posted : January 28, 2019
Sponsor:
Collaborators:
M.D. Anderson Cancer Center
Montefiore Medical Center
H. Lee Moffitt Cancer Center and Research Institute
New York Presbyterian Hospital
Information provided by (Responsible Party):
Opsona Therapeutics Ltd.

Tracking Information
First Submitted Date  ICMJE January 21, 2015
First Posted Date  ICMJE February 16, 2015
Last Update Posted Date January 28, 2019
Study Start Date  ICMJE January 2015
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 30, 2018)
  • 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 ]
  • Tolerability of OPN-305 as monotherapy based on adverse events [ Time Frame: 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 9, 2015)
  • 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 ]
  • Tolerability of OPN-305 as monotherapy based on adverse events [ Time Frame: 16 weeks ]
  • Tolerability of OPN-305 in combination with AZA based on adverse events [ Time Frame: 32 weeks ]
Change History Complete list of historical versions of study NCT02363491 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2018)
  • Hematological response based on International Working Group (IWG) 2000/2006 [ Time Frame: 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 ]
  • Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies) [ Time Frame: day 1, weeks 4, 8, 16, 24 and 32 ]
  • Incidence of infections [ Time Frame: 36 weeks ]
  • Pharmacokinetic profile of OPN-305 (maximum concentration (Cmax)) [ Time Frame: 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 ]
  • 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) ]
  • Correlation of clinical response with cytogenical observations [ Time Frame: 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
Original Secondary Outcome Measures  ICMJE
 (submitted: February 9, 2015)
  • Hematological response based on IWG 06 criteria of OPN-305 alone (16 weeks) and in combination with azacitidine on, transfusion independence and lack of progression to high risk MDS or AML (32 weeks) [ Time Frame: wks 16 and 32 ]
  • Cytokine levels in serum (TNFα, IL-1β, IL-6, IL-10, IL-12,and IFN-γ) [ Time Frame: wks 16 and 32 ]
  • Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies) [ Time Frame: wks 16 and 32 ]
  • Incidence of infections [ Time Frame: wks 16 and 32 ]
  • Pharmacokinetic profile of OPN-305 (Cmax, tmax, AUCinf, t1/2, CL, Vd) [ Time Frame: wks 4, 8, 12, 16, 20, 24, 28, 32 ]
  • OPN-305 receptor occupancy in blood, bone marrow cells and stroma [ Time Frame: wks 4, 8, 12, 16, 20, 24, 28, 32 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome
Official Title  ICMJE 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)
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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Myelodysplastic Syndrome
Intervention  ICMJE Drug: OPN-305
For the dose confirming part of the study, patients will receive a starting dose of 5 mg/kg OPN-305.
Study Arms  ICMJE Experimental: OPN-305
OPN-305
Intervention: Drug: OPN-305
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 24, 2019)
96
Original Estimated Enrollment  ICMJE
 (submitted: February 9, 2015)
40
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02363491
Other Study ID Numbers  ICMJE OPN-305-106
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Opsona Therapeutics Ltd.
Study Sponsor  ICMJE Opsona Therapeutics Ltd.
Collaborators  ICMJE
  • M.D. Anderson Cancer Center
  • Montefiore Medical Center
  • H. Lee Moffitt Cancer Center and Research Institute
  • New York Presbyterian Hospital
Investigators  ICMJE
Principal Investigator: Guillermo Garcia Manero, MD M.D. Anderson Cancer Center
PRS Account Opsona Therapeutics Ltd.
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP