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First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT04675996
Recruitment Status : Recruiting
First Posted : December 19, 2020
Last Update Posted : February 7, 2022
Sponsor:
Information provided by (Responsible Party):
InteRNA

Tracking Information
First Submitted Date  ICMJE December 8, 2020
First Posted Date  ICMJE December 19, 2020
Last Update Posted Date February 7, 2022
Actual Study Start Date  ICMJE December 18, 2020
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 15, 2020)
  • Incidence and severity of treatment-related adverse events and serious adverse events [ Time Frame: Up to 24 months ]
    Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE criteria v 5.0, incidence of dose limiting toxicities (DLTs), adverse events leading to discontinuation and deaths
  • Recommended Phase 2 Dose of INT-1B3 [ Time Frame: Up to 24 months ]
    Based on dose-limiting toxicities, the maximal tolerated dose and all other available safety, pharmacokinetic/pharmacodynamic data as assessed by the cohort review committee
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 15, 2020)
  • Area under the curve [ Time Frame: Up to 24 months ]
    Area under the plasma concentration time curve of INT-1B3
  • Maximum plasma concentration [ Time Frame: Up to 24 months ]
    Highest observed plasma concentration of INT-1B3
  • Time of maximum plasma concentration [ Time Frame: Up to 24 months ]
    Time to reach highest observed plasma concentration of INT-1B3
  • Half-life [ Time Frame: Up to 24 months ]
    Plasma concentration half-life of INT-1B3
  • Objective response rate of INT-1B3 [ Time Frame: Up to 24 months ]
    Objective response rate according to standard criteria by RECIST1.1
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE First-in-Human Study of INT-1B3 in Patients With Advanced Solid Tumors
Official Title  ICMJE Phase I/Ib, Open-label, Multiple Ascending Dose, First-in-Human Study, to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of INT-1B3 in Patients With Advanced Solid Tumors
Brief Summary This is a 2 part, multi-center, open-label, First-in-Human clinical study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of INT-1B3 in the treatment of patients with advanced solid tumors.
Detailed Description

The investigational medicinal product INT-1B3 is a lipid nanoparticle formulated microRNA (miR-193a-3p) mimic destined for therapeutic intervention in oncology. Preclinical work showed that INT-1B3 has a multi-target mechanism of action with an anti-proliferative, anti-metastatic, anti-migration, cell cycle disruption, induction of apoptosis effect and modulation on the tumor microenvironment leading to significant induction of T cell-mediated immune response.

The first part of the study (Phase I) is a dose-escalation phase to determine the maximal tolerated dose and the recommended Phase 2 dose, as well as the safety profile of INT-1B3 in patients with advanced malignancies.The subsequent expansion phase of the study (Phase Ib) will further explore safety, pharmacokinetics, pharmacodynamic responses, and antitumor activity of INT-1B3 in patients with selected cancer types treated at the recommended phase 2 dose.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: INT-1B3
60-min i.v. infusions twice per week in 21-day cycles
Study Arms  ICMJE Experimental: Phase 1/1b

Phase 1: dose escalation phase with a 'hybrid' 3+3 design in all-comers cancer patients. Approximately 30 patients will be included.

Phase 1b: dose expansion phase in selected tumor types at the recommended phase 2 dose. Approximately 50 patients will be included.

Intervention: Drug: INT-1B3
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 15, 2020)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2024
Estimated Primary Completion Date December 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patient provided a signed written informed consent before any screening procedure
  2. Patient is male or female, ≥18 years of age (adult patients)
  3. Patient with histologically or cytologically confirmed advanced and/or metastatic solid tumor, with progressive disease at baseline, for whom no standard treatment is available or who have declined standard therapy
  4. Patient with evaluable disease per RECIST v1.1, iRECIST
  5. Patient with a predicted life expectancy of > 12 weeks
  6. Patient with Eastern Cooperative Oncology Group performance status of grade 0 - 1
  7. Patient with hemoglobin ≥ 9.0 g/dL, platelet count ≥ 75×109/L, and absolute neutrophil count ≥ 1.0×109/L
  8. Patient with adequate renal function
  9. Patient with adequate liver function
  10. Patient with adequate coagulation tests
  11. Female patient of childbearing potential and males should use effective contraception
  12. Patient is able and willing to comply with the protocol and the restrictions and assessments therein

Exclusion Criteria:

  1. Patients on any other anti-cancer therapy, unless at least 4 weeks (or 5 half-lives, whichever is shorter), have elapsed since the last dose before the first administration of INT-1B3. At least 2 weeks should have elapsed since receiving non-palliative radiotherapy.
  2. Patient with known central nervous system (CNS) metastases, unless previously treated and well-controlled for at least 1 month (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart)
  3. Patient with concomitant second malignancies unless curatively treated at least 2 years before study entry with no additional therapy required or anticipated to be required during the study period
  4. Patient with major surgery within 5 weeks before initiating treatment or with minor surgical procedure within 7 days before initiating treatment
  5. Patient with active autoimmune disease or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade ≥ 2, except for residual endocrinopathy adequately substituted, vitiligo, Type 1 diabetes mellitus or psoriasis not requiring systemic therapy (>10mg prednisone equivalent)
  6. Patient with toxicity (except for alopecia) related to prior anti-cancer therapy and/or surgery, unless the toxicity is either resolved, returned to baseline or grade 1
  7. Patient with any active neuropathy > Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0)
  8. Patient with any condition requiring concurrent use of systemic immunosuppressants or corticosteroids at a daily dose > 10 mg prednisone equivalent or other immunosuppressive medications within 14 days of study medication administration
  9. Patient with evidence of active infection that requires systemic antibacterial, antiviral, or antifungal therapy ≤ 7 days before the first dose of study medication
  10. Patient with uncontrolled or significant cardiovascular disease
  11. Patient with known active or chronic hepatitis B or C (unless treated with no detectable virus)
  12. Patient with known history of exposure to human immunodeficiency virus (HIV)
  13. Patient with any known or underlying medical, psychiatric condition, and/or social situations that, in the opinion of the investigator, would limit compliance with study requirements
  14. Patient with history of allergy to the study medication or any of its excipients
  15. Patient that received packed red blood cells or platelet transfusion within 2 weeks of the first dose of study medication
  16. Female patient: pregnant or breastfeeding
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: Karlijn Kroon, MD +31 30 760 76 20 kroon@interna-technologies.com
Listed Location Countries  ICMJE Belgium,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04675996
Other Study ID Numbers  ICMJE INT1B3-CLIN-101
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party InteRNA
Original Responsible Party Same as current
Current Study Sponsor  ICMJE InteRNA
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Roel Schaapveld, PhD InteRNA
PRS Account InteRNA
Verification Date February 2022

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