Study to Determine Optimal Dose, Evaluate the Efficacy and Safety of PRG-N-01 in Patients With Neurofibromatosis Type II

NCT07131722 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: PRG-NF-001
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to learn if Trineumin(Code name:PRG-N-01) works to treat Neurofibromatosis Type II(NF2) in adults. It will also learn about the safety and tolerability and toxicity of PRG-N-01. The main questions it aims to answer are:

• What dose was determined as the Maximum Tolerated Dose (MTD) of Trineumin?
• What dose was explored as the optimal effective dose of Trineumin based on radiographic response?
• Does Trineumin reduce tumor size or improve participants' quality of life, including hearing function?
• What medical problems do participants have when taking Trineumin? Participants will:
• Take Trineumin every day for 96 weeks
• Visit the clinic once 1, 4, 8, 12, 18week and every 12 weeks and for checkups and tests

Conditions

Neurofibromatosis Type II; NF2

Outcome Measures

Primary Outcomes (8)

• Phase 1_Incidence of Dose-Limiting Toxicities (DLTs)

  Incidence of DLTs will be assessed to determine the MTD and RP2D based on predefined criteria.

  Each treatment group at the 12-week time point after IP administration

• Phase 1_Maximum Tolerated Dose (MTD)

  it determine the MTD based on predefined criteria.

  Each treatment group at the 12-week time point after IP administration

• Phase 1_ Recommended Phase 2 Dose (RP2D)

  it determine the RP2D based on predefined criteria.

  Each treatment group at the 12-week time point after IP administration

• Phase2a_Maximum tumor size change rate of Radiographic Tumor Response

  Based on best overall response (BOR), ORR, DOR, PFS, and changes in tumor size from baseline using up to 4 target lesions.

  From baseline excluding week 24 to week 96 at 12-week intervals

• Phase2a_best overall response (BOR) of Radiographic Tumor Response

  Based on best overall response (BOR), ORR, DOR, PFS, and changes in tumor size from baseline using up to 4 target lesions.

  From baseline excluding week 24 to week 96 at 12-week intervals

• Phase2a_Objective response rate (ORR) of Radiographic Tumor Response

  Based on best overall response (BOR), ORR, DOR, PFS, and changes in tumor size from baseline using up to 4 target lesions.

  From baseline excluding week 24 to week 96 at 12-week intervals

• Phase2a_Duration of response (DOR) of Radiographic Tumor Response

  Based on best overall response (BOR), ORR, DOR, PFS, and changes in tumor size from baseline using up to 4 target lesions.

  From baseline excluding week 24 to week 96 at 12-week intervals

• Phase2a_Progression-free survival (PFS) of Radiographic Tumor Response

  Based on best overall response (BOR), ORR, DOR, PFS, and changes in tumor size from baseline using up to 4 target lesions.

  From baseline excluding week 24 to week 96 at 12-week intervals

Secondary Outcomes (10)

• Phase1_Progression-free survival (PFS) of Radiographic Tumor Response

  From baseline to week 96 at 12-week intervals

• Phase1_Duration of response (DOR) of Radiographic Tumor Response

  From baseline to week 96 at 12-week intervals

• Phase1_Objective response rate (ORR) of Radiographic Tumor Response

  From baseline to week 96 at 12-week intervals

• Phase1_best overall response (BOR) of Radiographic Tumor Response

  From baseline to week 96 at 12-week intervals

• Phase1_Maximum tumor size change rate of Radiographic Tumor Response

  From baseline to week 96 at 12-week intervals

Other Outcomes (18)

• Phase2a_ Exploratory Analysis of Biomarker Expression in Blood

  Day 1,Week 12,Week 36

• Phase 1,2a_ AUC last of Day1

  Day 1, Day 7, and At every visit until week 96

• Phase 1,2a_ AUCinf of Day1

  Day 1, Day 7, and At every visit until week 96

Study Arms (3)

Trineumin Dose Escalation Arm

EXPERIMENTAL

Subjects receive Trineumin(Code: name: PRG-N-01) orally once daily across six sequential dose cohorts. Dose escalation follows an accelerated titration design (Cohort 1), a 3+3 design (Cohort 2), and a rolling 6 design thereafter. Dosing proceeds unless dose-limiting toxicities (DLTs) are observed.

Drug: Trineumin

Trineumin Low Dose (Phase 2a)

EXPERIMENTAL

Subjects receive Trineumin(Code: name: PRG-N-01) at the selected lower dose (e.g., RP2D or sub-RP2D level) once daily. Subjects are randomized in Phase 2a.

Drug: Trineumin

Trineumin High Dose (Phase 2a)

EXPERIMENTAL

Subjects receive Trineumin(Code: name: PRG-N-01) at a higher dose once daily in Phase 2a. Subjects are randomized to this arm.

Drug: Trineumin

Interventions

Trineumin DRUG

Trineumin(Code name: PRG-N-01) is administered orally once daily. The study includes six dose levels. Dose escalation decisions are based on observed DLTs.

Trineumin Dose Escalation Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects aged 18 years or older at screening
• Subjects diagnosed with NF2 clinically or genetically, according to the I-NF-DC 2022 updated NF2 diagnostic criteria
• Subjects with tumors due to NF2 who require treatment if they meet one of more of the criteria below but cannot undergo surgical treatment due to high risk of side effects from surgery (e.g., damage to nerve function).
• (1) Subjects with progressive tumors (VS, non-VS, meningiomas, ependymomas) confirmed on MRI within 36 months prior to screening (2) Subjects with clinical symptoms (decreased function of affected nerves, such as hearing loss, uncontrolled pain, shortness of breath, difficulty swallowing, decreased motor function, and decreased gait) as judged by the investigator 4) Subjects with ECOG performance status 0 - 1 or Karnofsky performance status 70 or higher 5) Subjects who have appropriate hematological, liver, renal, and blood coagulation functions confirmed based on the following criteria at screening: 6) Subjects who have appropriate cardiac and pulmonary functions confirmed based on the following criteria at screening: 7) Subjects who agree to use sunscreen during the clinical study period. 8) Subjects (or the subject's legal representative) who voluntarily consent and provide written informed consent to participate in this clinical study.
• \) (Only for Phase 2a) Subjects with one or more measurable NF2-related tumors confirmed on MRI at screening

You may not qualify if:

• \) Subjects who have the following past or current medical history confirmed during screening:
• (1) Malignant tumor requiring treatment (chemotherapy or radiotherapy) or with disease progression within 2 years prior to screening (2) The following heart-related history
• Uncontrolled hypertension at screening (DBP ≥100 mmHg or SBP ≥160 mmHg despite treatment)
• Acute coronary syndrome (ACS) within 24 weeks of baseline, clinically significant arrhythmia, cardiomyopathy, unstable angina, NYHA II-IV heart failure, or severe valvular heart disease
• Interstitial lung disease or pulmonary fibrosis
• Cystitis or urinary obstruction within 12 weeks prior to screening
• Blood coagulation disorder
• Severe or active infectious disease requiring antibiotics, antivirals, etc. within 4 weeks prior to screening
• Gastrointestinal disease that currently makes oral administration difficult or may affect absorption (e.g., celiac disease, Crohn's disease, intestinal resection)
• Other diseases that are sufficient to affect the clinical study results at the investigator's discretion.
• \) Subjects who have confirmed or need the following drug treatments:
• Chemotherapy, immunotherapy, or myelosuppressive chemotherapy within 4 weeks prior to screening (but, within 6 weeks prior to screening for nitrosourea agents or mitomycin C)
• Monoclonal antibody therapy within 12 weeks prior to screening (but, allowing if more than 3 half-lives have elapsed); stem cell transplantation (but, allowing if there is no evidence of active graft-versus-host disease and more than 12 weeks have elapsed since transplantation)
• Other investigational drugs or devices within 4 weeks prior to screening
• Corticosteroids such as prednisone and prednisolone within 1 week prior to screening (but, allowing if treated with low doses)

Sponsors & Collaborators

• PRG Science & Technology Co., Ltd.: lead

MeSH Terms

Conditions

Neurofibromatosis 2

Condition Hierarchy (Ancestors)

Neuroma, Acoustic; Neurilemmoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neurofibromatoses; Neurofibroma; Nerve Sheath Neoplasms; Neoplasms, Nerve Tissue; Neuroma; Neoplastic Syndromes, Hereditary; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Otorhinolaryngologic Neoplasms; Cranial Nerve Neoplasms; Cranial Nerve Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential Assignment, non-Randomized (Phase 1), then Parallel Assignment, Randomized (Phase 2a)

Study Record Dates

• First Submitted: July 1, 2025
• First Posted: August 20, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: January 23, 2026

Record last verified: 2025-08