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A Study to Evaluate the Safety, Tolerability and Efficacy of RZ-001 With Valganciclovir (VGCV) in Subjects With Glioblastoma

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.
 
ClinicalTrials.gov Identifier: NCT06102525
Recruitment Status : Not yet recruiting
First Posted : October 26, 2023
Last Update Posted : October 26, 2023
Sponsor:
Information provided by (Responsible Party):
Rznomics, Inc.

Study Description
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Brief Summary:
This is a Phase 1/2a, open-label study to evaluate the safety, tolerability, immunogenicity, and preliminary clinical activity of RZ-001 administered in combination with VGCV in subjects with hTERT-positive GBM.

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: RZ-001 Combination Product: VGCV Phase 1 Phase 2

Detailed Description:

The study consists of 2 parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2).

Part 1 consists of dose escalation exploring MTD/RP2D for intratumoral (IT) injection.

Part 2 will consist of dose expansion exploring clinical activity for the optimal fixed dose based on the results of Part 1.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2a, Open-label, Multicenter, Dose Escalation and Dose Expansion Study Evaluating the Safety, Tolerability, and Efficacy of RZ-001 in Combination With Valganciclovir in Subjects With Glioblastoma
Estimated Study Start Date : October 2023
Estimated Primary Completion Date : March 2029
Estimated Study Completion Date : May 2029

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1 Cohort 1
RZ-001 Dose 1 and VGCV
 Drug: RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
Other Name: Ad-ECRT-122T

Combination Product: VGCV
VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.
Other Name: Valganciclovir
Experimental: Part 1 Cohort 2
RZ-001 Dose 2 and VGCV
 Drug: RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
Other Name: Ad-ECRT-122T

Combination Product: VGCV
VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.
Other Name: Valganciclovir
Experimental: Part 1 Cohort 3
RZ-001 Dose 3 and VGCV
 Drug: RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
Other Name: Ad-ECRT-122T

Combination Product: VGCV
VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.
Other Name: Valganciclovir
Experimental: Part 1 Cohort 4
RZ-001 Dose 4 and VGCV
 Drug: RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
Other Name: Ad-ECRT-122T

Combination Product: VGCV
VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.
Other Name: Valganciclovir
Experimental: Part 1 Cohort 5
RZ-001 Dose 5 and VGCV
 Drug: RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
Other Name: Ad-ECRT-122T

Combination Product: VGCV
VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.
Other Name: Valganciclovir
Experimental: Part 2
RZ-001 Dose 6 and VGCV
 Drug: RZ-001
Recombinant adenovirus harboring the modified ribozyme construct with HSV-tk as a therapeutic transgene
Other Name: Ad-ECRT-122T

Combination Product: VGCV
VGCV, used in a subject after RZ-001 administration, is a nucleoside analog that is metabolized by HSV-tk and other cellular kinases to form the cytotoxic nucleotide analog ganciclovir triphosphate. An approved oral VGCV will be used in the proposed clinical study of RZ-001.
Other Name: Valganciclovir


Outcome Measures
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Primary Outcome Measures :
  1. Number of dose limiting toxicities (DLTs) [ Time Frame: Day 1 to Day 28 ]
  2. Maximum tolerated dose (MTD) or maximum administered dose (MAD) dose(MAD) and select the recommended Phase 2 dose (RP2D) of RZ-001 in combination with VGCV [ Time Frame: Day 1 to Day 28 ]
  3. Number of participants with treatment-related adverse events as assessed by NCI-CTCAE [ Time Frame: Day 1 to Day 28 ]
    Adverse events (AEs) as characterized by type, number, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]), timing, seriousness, and relationship to RZ-001

  4. Number of participants with significant laboratory abnormalities as assessed by NCI-CTCAE [ Time Frame: Day 1 to Day 28 ]
    Clinically significant laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI-CTCAE), timing, and relationship to RZ-001

  5. Overall survival (OS) [ Time Frame: Day 1 to Day 15 ]

Secondary Outcome Measures :
  1. Change in concentration of serum vascular endothelial growth factor (VEGF) [ Time Frame: Day 1 to Day 28 ]
  2. Change in concentration of serum anti-adenovirus antibody [ Time Frame: Day 1 to Day 28 ]
  3. Overall response rate (ORR) [ Time Frame: Day 1 to Day 15 ]
  4. Duration of response (DOR) [ Time Frame: Day 1 to Day 15 ]
  5. Progression-free survival (PFS) per modified Response Assessment for Neuro-Oncology (mRANO) [ Time Frame: Day 1 to Day 15 ]
  6. Overall survival (OS) [ Time Frame: Day 1 to Day 15 ]
  7. Neurologic function assessment using the Neurologic Assessment in Neuro-Oncology (NANO) scale ranging from 0 to 3 in each assessment domain [ Time Frame: Day 1 to Day 15 ]

Other Outcome Measures:
  1. Concentration of adenovirus DNA in Plasma at specified timepoints [ Time Frame: Day 1 to Day 28 ]
  2. Change in concentration of serum anti-adenovirus antibody [ Time Frame: Day 1 to Day 28 ]
  3. Change in concentration of serum cytokines [ Time Frame: Day 1 to Day 28 ]
    Serum cytokines including interleukins 1 (IL-1), IL-6, IL-10, IL-27, interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α)

  4. Concentration of biomarker in peripheral blood [ Time Frame: Day 1 to Day 28 ]
    Activation of immune cell subsets (including but not limited to cluster of differentiation 3 [CD3], CD4, CD8, B cell, natural killer [NK] cell)

  5. Concentration of biomarker in fresh tumor biopsy tissue [ Time Frame: Day 1 to Day 28 ]
    Tumor-related RNA and T cell infiltration and activation


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

Inclusion Criteria:

  • Adult males and females
  • Histologically-confirmed grade 4 astrocytoma, GBM, per The 2021 WHO Classification of CNS Tumors.
  • hTERT positive expression confirmed during the screening period
  • ECOG score of ≤ 2
  • KPS ≥ 60
  • Life expectancy ≥ 3 months

Exclusion Criteria:

  • Diagnosis of other malignant tumors within 5 years prior to RZ-001 administration.
  • Have extracranial metastases of the tumor cells
  • Current or history of HIV positive
  • Not suitable for inclusion judged by the investigator
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT06102525


Contacts
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Contact: Rznomics Inc. +82317068730 rznomics@rznomics.com
Contact: Hyunjin Yoon +82-31-701-8735 hjyoon@rznomics.com

Sponsors and Collaborators
Rznomics, Inc.
Investigators
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Principal Investigator: Doo Sik Kong Samsung Medical Center
Principal Investigator: Chang Ki Hong Asan Medical Center
More Information
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Responsible Party: Rznomics, Inc.
ClinicalTrials.gov Identifier: NCT06102525    
Other Study ID Numbers: RZ-001-201
First Posted: October 26, 2023    Key Record Dates
Last Update Posted: October 26, 2023
Last Verified: October 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
 Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Valganciclovir
Antiviral Agents
Anti-Infective Agents