Study of an AAV Mediated Dual-Payload Gene Therapy in Patients With High Grade Glioma
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-70
SponsorTrogenix ltd
About this trial
The goal of this clinical trial is to first define the Safety and Optimal Biological Dose (OBD) of study drug TGX-007 and to then further investigate the safety and efficacy in patients with newly diagnosed or recurrent Glioblastoma.
TGX-007 is a gene therapy drug delivered by a harmless adeno-associated virus (AAV) vector which delivers two combined therapeutic payloads to enable killing of proliferative cells and activation of an anti-tumour immune response. One is herpes simplex virus thymidine kinase (HSV-tk), which converts the pro-drug valaciclovir into an active drug that can kill tumour cells and the other is interleukin 12 (IL-12), which activates the body's immune system to recognise and fight the tumour.
Patients newly diagnosed with glioblastoma suitable for standard of care surgery and chemoradiotherapy or patients with recurrent glioblastoma suitable for further surgery may be eligible for the study. Patients will receive TGX-007 by a direct intratumoural injection and will then take the pro-drug valacyclovir orally for up to 21 days before proceeding to standard of care surgery.
The study is split into two phases. Phase I will treat patients at different dose levels of TGX-007 to identify the Optimal Biological Dose that will be used to further expand the study into Phase II. Phase II will expand the number of patients treated at the selected OBD to investigate how effective TGX-007 is at treating newly diagnosed and recurrent GBM.
Approximately 68 people aged 18-70 will take part in the study.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Aged 18-70 years
Karnofsky performance status ≥70
Newly diagnosed patients: Unifocal, unilateral high-grade glioma based on MRI
Recurrent patients: First radiological progression (as determined by the multidisciplinary team [MDT]) of GBM previously treated with standard care surgery and chemoradiotherapy. Patients must have a prior confirmed histological/molecular diagnosis of GBM
Disqualifiers
Patient who is pregnant, lactating or planning pregnancy during the course of the study
Immunodeficiency or active auto-immune disease requiring systemic therapy.
Active viral, bacterial or fungal infection requiring concurrent antivirals or antibiotics within 7 days of surgery
Live vaccine within 28 days prior to Day 0
Trial design
Design model
Sequential
Treatments tested in this trial
TGX-007
DrugTGX-007 administered as single intratumoural injection
Valaciclovir
DrugOral valaciclovir administered 3 times daily for 14 - 21 days
Treatment groups
68 Participants
are divided into 3 treatment groupsGroup A: Dose FindingExperimental treatment 2 interventions
Group B: Newly Diagnosed ExpansionExperimental treatment 2 interventions
Group C: Recurrent Glioblastoma ExpansionExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Safety and tolerability of TGX-007 when administered to patients with newly diagnosed HGG or recurrent GBM and to identify the OBD
Incidence of AEs/SAEs, incidence of DLT within 28 days of TGX-007 administration at each dose level, and incidence of HSV-tk mRNA expression, or equivalent, in tissue
Time frame
Day 0 (TGX-007 injection) to 28 days post administration of TGX-0072
Overall Survival rate of patients with newly diagnosed HGG or recurrent GBM treated with TGX-007
Overall Survival at 18 months (newly diagnosed patients) and 6 months (recurrent patients).
Time frame
Day 0 (TGX-007 injection) to 18 months (newly diagnosed); Day 0 (TGX-007 injection) to 6 months (recurrent patients)Secondary outcomes
1
Overall Survival
Median OS and OS up to 5 years by Kaplan-Meier analysis.
Time frame
Baseline to 5 year follow up2
Viral shedding in body fluids following delivery of TGX-007.
Detection of vector genomes by droplet digital polymerase chain reaction (ddPCR) in patient samples
Time frame
Baseline until 3 consecutive negative samples, assessed up to 5 years post treatment.3
Progression-free survival (PFS) of patients with newly diagnosed HGG or recurrent GBM treated with TGX-007.
PFS as determined by the Investigator
Time frame
Date of surgery to the earliest date progression is documented or death from any cause, measured out to 5 years post surgery4
Objective response rate (ORR) of patients with newly diagnosed HGG or recurrent GBM treated with TGX-007.
ORR on pre-operative MRI per Response Assessment in Neuro-Oncology 2.0 (RANO 2.0) criteria.
Time frame
Baseline to 21 daysSponsors and contacts
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Source ClinicalTrials.gov