Safety and Efficacy of NRG-103 Injection in the Treatment of Recurrent Glioblastoma Patients

Clinical Study on the Safety and Efficacy of NRG-103 Injection in the Treatment of Recurrent Glioblastoma Patients

The goal of this clinical trial is to learn if NRG103 works to treat recurrent GBM in adults. It will also learn about the safety of NRG103.

The main questions it aims to answer are:

Does NRG103 prolong overall survival or disease-free survival in patients with GBM? What medical problems do participants have when receiving NRG103 treatment? Researchers will give patients with NRG103 to see if NRG103 works to treat recurrent GBM.

Participants will:

Receive NRG103 twice in 14 days Visit the clinic once every 2 weeks for checkups and tests Keep a diary of their symptoms

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma (GBM)
• Intervention / Treatment: Drug: NRG-103

Detailed Description

The annual incidence rate of malignant brain tumors in China is 4.2/100000, and GBM accounts for 50.9%. GBM is highly invasive and malignant. After undergoing anti-tumor treatments such as surgery, radiotherapy, and chemotherapy, the short-term recurrence rate is extremely high. The median survival time after recurrence is only 9 months, and the 1-year survival rate is 30%. It is urgent to explore new therapy strategy.

Transgenic oncolytic virus therapy for GBM is an emerging anti-tumor therapy. The genetically engineered oncolytic virus has improved selectivity towards tumor cells, replicating and lysing only within infected tumor cells, while activating the body's immune system to launch a more extensive attack on tumors. At present, various genetically modified oncolytic viruses targeting GBM have entered the clinical trial stage both domestically and internationally. For example, G47Δ, with superior anti-tumor activity and good safety in early clinical trials, has been conditionally approved for marketing in Japan for the treatment of malignant gliomas. DNX-2401, JL15003, and others are also in the early stages of clinical research. NRG-103 is an innovative gene therapy drug developed based on the in situ trans-differentiation technology. Through multiple mutation modifications of the adenovirus genome, it can enhance the specific recognition and killing effect of oncolytic virus on GBM tumor cells without being limited by tumor gene phenotype, and regulate the immune microenvironment to induce stronger anti-tumor immune response. In addition, the two transcription factors expressed on NRG-103 can efficiently transdifferentiate residual GBM tumor cells into non tumor like neuronal cells, in order to achieve the goal of delaying tumor recurrence and long-term survival. NRG-103 exhibits significant anti-tumor activity and clear in situ trans-differentiation effects in preclinical models, providing scientific evidence for the potential clinical efficacy of NRG-103.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zhiqiang Li; Phone Number: +86-18907123005; Email: lizhiqiang@whu.edu.cn
• Study Contact Backup: Name: Feng Tang; Phone Number: +86-18326163693; Email: zntang@whu.edu.cn

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Zhongnan Hospital of Wuhan University
      • Contact: Zhiqiang Li; Phone Number: +8618907123005; Email: lizhiqiang@whu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age≥18 years.
2. Patients must have histologically or cytologically confirmed glioblastoma(WHO 2021).
3. Patients have experienced recurrence (RANO 2.0) after previous anti-tumor treatments, including the recurrent tumor has been surgically removed and an Ommaya reservoir has been placed inside the tumor cavity.
4. The relevant adverse reactions from the previous treatment have been restored to ≤1 level(NCI-CTCAE v5.0).
5. Karnofsky Performance Score≥70.
6. Stable doses of dexamethasone during the week prior to inclusion.
7. Adequate bone marrow reserve: White blood cell count>2.0 × 109/L, neutrophil count>1.0 × 109/L, platelet count>100 × 109/L, international normalized ratio ≤1.5 times ULN, and activated partial thromboplastin time≤1.5 times ULN.
8. Normal heart, renal and liver function.
9. Effective method of contraception for patients and their partners.
10. Written informed consent.

Exclusion Criteria:

1. Allergy to the components of the test drug and contrast agent.
2. Unable to undergo imaging examinations required for the research.
3. A history of cell therapy, gene therapy, or oncolytic virus therapy.
4. Undergoing other clinical trials.
5. A history of anti-tumor vaccines or other immunomodulatory drugs with 4 weeks.
6. A history of other type of malignant tumors.
7. Unexplained fever.
8. A history of autoimmune disease.
9. A history of immunodeficiency, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation.
10. Active hepatitis B, or hepatitis C.
11. Severe heart disease (NYHA III or IV), or poorly controlled diabetes.
12. Two or more GBM lesions.
13. GBM lesion located in the brainstem, cerebellum, posterior fossa, or spinal cord, as well as leptomeningeal diseases.
14. A history of diffuse subarachnoid and subarachnoid diseases.
15. GBM lesion invades the ventricular wall or tumor cavity communicates with the ventricle after surgery.
16. A history of encephalitis, multiple sclerosis, or other central nervous system infections.
17. Cerebral herniation syndrome.
18. Pregnant and lactating women.
19. Other situations that the researcher deems unsuitable for entry into the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: NRG-103; NRG-103 is an innovative gene therapy drug developed based on the in situ trans-differentiation technology. Through multiple mutation modifications of the adenovirus genome, it can enhance the specific recognition and killing effect of oncolytic virus on GBM tumor cells without being limited by tumor gene phenotype, and regulate the immune microenvironment to induce stronger anti-tumor immune response. In addition, the two transcription factors expressed on NRG-103 can efficiently transdifferentiate residual GBM tumor cells into non tumor like neuronal cells, in order to achieve the goal of delaying tumor recurrence and long-term survival.

Drug: NRG-103; NRG-103 is an oncolytic virus, which can kill GBM cells via three manners.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	The participants will be followed until disease progression by RANO criteria	6 months after NRG-103 treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	The participants will be followed until death	12 months after NRG-103 treatment

Collaborators and Investigators

• Sponsor: Zhongnan Hospital
• Investigators: Principal Investigator: Zhiqiang Li, Zhongnan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 24, 2024
• First Submitted That Met QC Criteria: January 1, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Glioblastoma;Oncolytic virus;NRG103;Trans-differentiation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: NRG103001; ChiCTR2400093705 (Other Grant/Funding Number: NEURAGEN, Suzhou, China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data related to this clinical trial will be protected by Zhongnan Hospital

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No