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

NCT02363491

Description:

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).

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Phase I/II Study of OPN-305 in Second-line Lower Risk Myelodysplastic Syndrome
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: OPN-305-106
  • NCT ID: NCT02363491

Conditions

  • Myelodysplastic Syndrome

Interventions

DrugSynonymsArms
OPN-305OPN-305

Purpose

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).

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
OPN-305ExperimentalOPN-305
  • OPN-305

Eligibility Criteria

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

Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Hematological response based on IWG06 criteria, transfusion independence and lack of progression to high risk MDS or AML
Time Frame:wk 36
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Immunogenicity of OPN-305 (Measurement of anti drug antibodies and neutralizing antibodies)
Time Frame:day 1, wks 4, 8, 16, 24 and 32
Safety Issue:
Description:
Measure:Incidence of infections
Time Frame:36 weeks
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Correlation of clinical response with cytogenic data eg expression, mutational to see if clinical response given by subset
Time Frame:wk 36
Safety Issue:
Description:
Measure:Correlation of clinical response with QOL questionnaire feedback in terms of symptoms and severity through study completion
Time Frame:wk 36
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Opsona Therapeutics Ltd.

Trial Keywords

    Last Updated

    October 11, 2016