Phase I single-blinded, randomized, placebo-controlled trial evaluating safety, tolerability, pharmacokinetics and pharmacodynamics of single injections of ascending doses of investigational drug product Mobilan (М-VM3) administered directly into the prostate of patients with prostate cancer.
Mobilan is a type V adenovirus carrying TLR5 receptor and its agonist, protein 502s. It's mechanism of action involves activation of immune system and extensive mobilisation of various immunocytes to administration locus. It's safety and tolerability is currently evaluated in first-in-man phase I study in prostate cancer patients. Treatment strategy for the disease (radical prostatectomy or active observation) will be determined by the Investigator in accordance with routine clinical practice of the hospital. Patients will be randomised in cohorts of 4 subjects, where 3 subjects will be administered with Mobilan (М-VM3), and one patient will be administered with placebo. The dose will be escalated from cohort to cohort, the decision on possible dose escalation will be made by Independent Safety Review Board.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
32
Mobilan (M-VM3), innovative experimental drug based on non-replicate adenoviral delivery system consisting genomic vector coding TLR5-receptor and its ligand 502s.
5% infusion solution of dextrose
Federal State Budgetary Institution "Russian Oncological Research Center named after N. N. Blokhin" of the Russian Academy of Sciences
Moscow, Russia
Moscow Scientific Research Institute of Oncology named after P. A. Hertsen of the Ministry of Health of the Russian Federation
Moscow, Russia
Moscow State Budgetary Healthcare Institution "City Clinical Hospital № 57" of Moscow Healthcare Department
Moscow, Russia
Frequency and intensity of adverse events (according to CTCAE v 4.03 classification)
Time frame: Baseline to up to 29 days after the drug administration
Exposure of Mobilan DNA vector in patient's peripheral blood
Using validated PCR assay
Time frame: Baseline to up to 29 days after the drug administration
Prostate-specific antigen (PSA) measure
Baseline PSA level will be taken from medical history
Time frame: On Day 29 after the drug administration
Immune cell count in whole blood of patients assessed with flow cytometry
Including leucocytes, lymphocytes, T-lymphocyte, leukocyte index, total T-lymphocytes, CD3, T-helper cells CD3 + CD4 +, T-cytotoxic CD3 + CD8 +, regulation index (CD4 / CD8), double-cells CD4 + / CD8 +, NK cells CD3-CD (16 + 56) +, TNK-cells CD3 + CD (16 +56) +, B-lymphocytes CD19 +, 0-lymphocytes
Time frame: Baseline to up to 29 days after the drug administration
Histopathological assessment of prostate tissue using Gleason grading system (if prostatectomy is made in the study period, and material is available for analysis)
The Gleason grading system is used to evaluate the stage of prostate cancer using samples from biopsy or post-surgical samples as follow: 1 - The cancerous prostate closely resembles normal prostate tissue. 2 - The tissue still has well-formed glands, but they are larger and have more tissue between them. 3 - The tissue still has recognizable glands, but the cells are darker. 4 - The tissue has few recognizable glands. 5 - The tissue does not have any or only a few recognizable glands.
Time frame: On Day 29 after the drug administration
Presence of protein 502s in blood plasma
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Moscow State University of Medicine and Dentistry
Moscow, Russia
Federal State Budgetary Institution "Saint Petersburg Clinical Scientific and Practical Center for Special types of medical care (Oncological)"
Saint Petersburg, Russia
Federal State Budgetary Institution "Scientific Research Oncology Institute named after N.N. Petrov" of the Ministry of Health of the Russian Federation
Saint Petersburg, Russia
Using ELISA assay
Time frame: Baseline to up to 29 days after the drug administration
Titer of 502 antibodies (AB) in peripheral blood serum
Using ELISA assay
Time frame: Baseline to up to 29 days after the drug administration
Histopathological assessment of prostate tissue using Irani scale (if prostatectomy is made in the study period, and material is available for analysis)
Irani J (1997) scale include histological assessment of slide mounts obtained after operation as follow: Degree of immune cell infiltration: 0 - No inflammatory cells, 1 - Scattered inflammatory cell infiltrate within the stroma without lymphoid nodules, 2 - Nonconfluent lymphoid nodules, 3 - Large inflammatory areas with confluence of infiltrate
Time frame: On Day 29 after the drug administration