Immuno-NF2 Main Study

JRCT ID: jRCT2031240607

Registered date:15/01/2025

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Patients with NF2 diagnosed with progressive schwannoma and HLA-A*24:02
• Date of first enrollment: 21/02/2025
• Target sample size: 26
• Study type: Interventional

Intervention(s)

Patients are randomly assigned to either a control or treatment group.
OCV-101/OTS-102 or placebo were emulsified together with incomplete Freund's adjuvant (Montanide ISA-51 VG, SEPPIC, Paris). OCV-101/OTS-102 or placebo were injected subcutaneously into infra-axillary and inguinal regions, once a week for 4 weeks and then once a month for 11 months (total of 15 injections over 12 months).

Outcome(s)

• Primary Outcome: The time from start of treatment until disease progression (PD, vestibular schwannoma)

Secondary Outcome

Efficacy endpoint
1) Proportion of subjects with a response of PR, MR, or SD at Visit 16 compared to baseline (Disease control rate)
2) Proportion of subjects with a response of PR, or MR at Visit 16 compared to baseline
3) Percentage change in target and non-target tumor volume from baseline
4) Percentage change in total tumor volume from baseline (target and non-target vestibular schwannoma)
5) Improvement rate of hearing at Visit 10 and 16 compared to baseline (WRS:10%<=)
6) Hearing change at Visit 16 compared to baseline
7) Change in ABR measurements at Visit 16 compared to baseline
8) Change in stabilometry measurements at Visit 16 compared to baseline
9) Change in the following test values at Visit 16 compared to baseline
- EuroQol 5 Dimension (EQ-5D-5L)
- The Penn Acoustic Neuroma Quality-of-Life scale (PANQOL)
- Dizziness Handicap Inventory (DHI)
- Tinnitus Handicap Inventory (THI)
10) Changes in immune response (cytotoxic T cell [CTL] induction) at Visit 16 compared to baseline

Safety endpoint
- Toxicity profile (frequency and severity)

Exploratory endpoint
- PTA

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

1) Written informed consent obtained from participant. For children below the age of 20, a parent(s) or legal guardian(s) can consent to the treatment of the child.
2) Participant must have a progressive NF2-related vestibular schwannoma with documented radiographic progression within the preceding 12 (+/-2) months of study registration defined as either: >= 20% increase in tumor volume or >= 2 mm increase in greatest linear dimension of tumor. Other chemotherapies are not permitted.
3) Announcement of a diagnosis
4) Positive genomic DNA typing for HLA-A* 24:02
5) Participant without symptom of brain hypertension must have a NF2-related vestibular schwannoma with the following qualities: Not amenable to surgery or radiation therapy for the next one year. This evaluation is performed by two or more neurosurgeons and otolaryngologists.
6) Age between 12 and 79 years
7) Eastern Cooperative Oncology Group (ECOG) performance status (PS): 0-2 (3, depending on the situation)
8) No surgery, chemotherapy, or irradiation for the tumors except vestibular schwannomas in the 4 weeks prior to enrolment
9) No severe adverse events after the prior chemotherapy (<= CTCAE [ver. 5.0] grade 2)
10) Participants must have at least one NF2-related vestibular schwannoma without prior radiation therapy (WRS < 85% and PTA [3-frequency (500, 1000, 2000 Hz)] <100.1dB).
11) Laboratory test values prior to vaccination (supportive therapy is not permitted)
- Hemoglobin level >=10 g/dl
- Platelet count >=75,000/microL
- Neutrophil count >=1500/microL
- Lymphocyte count >=1500/microL
- AST and ALT <= 3.0x the institutional normal upper limits
- Creatinine <= 1.5mg/dL

Exclude criteria

1) Prior peptide vaccine therapy (OCV-101 and/or OTS-102)
2) Malignant tumor requiring treatment (exc. carcinoma in situ and intramucosal carcinoma)
3) Participant who is unable to eat orally due to gastrointestinal lesions and require intravenous infusion, tube feeding, or high-calorie infusion for 24 hours or more.
4) Myelodysplastic syndrome and myeloproliferative disease
5) Prior allogeneic hematopoietic stem cell transplantation in two years
6) Moderate pleural effusion, ascites, and pericardial effusion (needing puncture)
7) Presence of uncontrollable severe infectious diseases
- HBs antigen, HBs antibody, HBc antibody, or HCV antibody-positive participant
- HIV antibody-positive participant
8) Hearing thresholds (a or b)
a. WRS >= 85%
b. PTA [3-frequency (500, 1000, 2000 Hz)] >= 100.1dB
9) Severe functional disorder (>= CTCAE [ver. 5.0] Grade 3)
10) Severe psychiatric, cognitive, or consciousness disorder
11) Uncontrolled diabetes
12) Enteroparalysis
13) Interstitial pneumonia or idiopathic pulmonary fibrosis (participant with past history of these diseases is not permitted)
14) Myocardial infarction, severe unstable angina, congestive heart failure, cerebrovascular disease, pulmonary embolism, deep venous thrombosis, other severe thrombo-embolisms and coronary artery bypass grafting within 12 months before obtaining consent.
15) Treatment-resistant hypertension
16) Arrhythmia heart failure requiring treatment
17) Unhealed wound (including fracture)
18) Hemorrhagic history such as blood coagulation disorder
19) Participant requiring continuous systemic administration of steroids or immunosuppressants (however, local administration, administration of prednisolone for acute sensorineural hearing loss including sudden deafness [<=60 mg/day, 2 weeks], and administration before imaging examinations for allergies are permitted)
20) Drug allergy for OCV-101, OTS-102, and incomplete Freund's adjuvant
21) Pregnancy or planning to become pregnant during the study period (male: 180 days after the last vaccination, female: 120 days after the last vaccination). Participant continuing breast-feeding after obtaining consent is not permitted.
22) Participating in other trials (non-interventional clinical is permitted)
23) Decision of unsuitability by the principal investigator or the physician in charge

Related Information

• Primary Sponsor: Toda Masahiro
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development (AMED)