Safety and Tolerability Clinical Trial of Different Doses of the Immunotherapeutic Drug Mobilan (M-VM3) and Placebo in Patients With Prostate Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Multicenter, Randomized, Single-blind Safety and Tolerability Clinical Trial of Different Doses of the Immunotherapeutic Drug Mobilan (M-VM3) and Placebo in Patients With Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Mobilan (M-VM3)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subscribed Informed consent for participation in the trial Men aged 45 to 75 years Patients with histologically verified prostate cancer, stage Т1-Т2, N0, M0 Patient's ECOG status 0-2 Negative tests for serologic markers of HIV-infection, viral hepatitis В and С, syphilis Patient and his partner should agree to use barrier contraception throughout the study period Exclusion Criteria: Failure to obtain Informed consent Clinical or radiological signs of metastases Indication to hormone therapy of prostate cancer Clinically significant cardiovascular diseases: Myocardial infarction within 6 months prior the screening Unstable stenocardia within 3 months prior the screening Severe circulation failure (FC III) Clinically significant arrhythmias Hypotension (systolic blood pressure < 86 mm Hg) or bradycardia with HR < 50 beats per min. Uncontrolled arterial hypertension (systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg.) Clinically significant CNS diseases at the screening Current infection or another severe or systemic disease which increases risk of treatment sequelae Pituitary gland or adrenal disorders in medical history Other malignant tumors within the last 5 years Other concomitant diseases in medical history which according to Investigator may aggravate during the study, including uncontrolled diabetes mellitus, rectal diseases, rectal fissures, hemorrhoid, rectal polyps, rectostenosis, inflammatory urinary diseases: chronic prostatitis, cystitis, urethral catheter, chronic urine retention. Complicated allergic history, systemic allergic reaction, any dietary allergy, intolerability, limitations or specific diets which according to the Investigator may be a contraindication for subject participation in the present study. Administration of drug products which have a marked effect on immune system within 3 previous months prior the screening, long-term intake of disaggregants (warfarin, low molecular heparin except for ThromboASS). Participation in other clinical studies or administration of investigational drug products within 30 days prior the screening, or persisting adverse reactions of any investigational drug product. Any clinically significant patient's health disorders and/or laboratory abnormalities not enlisted in the Protocol which are identified at the screening, and/or any reason which according to the Investigator may prevent the patient's participation in the study. Drug or alcohol abuse at the screening or in the past which according to the Investigator makes the patient ineligible for participation in the study: intake of more than 5 units of alcohol a week (1 unit of alcohol is equivalent to ½ liter of beer, 200 ml of vine or 50 ml of alcohol) or anamnestic data on alcoholism, narcomania, drug abuse and/or history of significant alcohol or drug abuse inducing drug dependence, within one year prior the screening visit. Vaccination made 14 days prior the study Smoking of more than 10 cigarettes a day Unability to understand or follow study instructions Lack of availability during 29 days after administration of the investigational drug product, fails to follow visit schedule Individual intolerability of the investigational drug product components Study withdrawal criteria: Any patient may refuse from the study participation on his own wish in any moment on any study stage. Principal Investigator may withdraw any patient from the study in the following cases: Investigator makes the decision that a patient should be withdrawn in his own best interests Patient develops any serious adverse reactions/events in the screening period Patient has been enrolled to the study with violations, or does not follow the protocol requirements Patient needs additional treatment in the screening period Sponsor has right to terminate the study in any moment. Regulatory authorities have right to terminate the study in any moment.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mobilan (M-VM3)<br>Patients with histologically verified non-metastatic prostate cancer (stage 1 or 2) treated with Investigational Drug Product | Drug: Mobilan (M-VM3)<br>* Mobilan (M-VM3), innovative experimental drug based on non-replicate adenoviral delivery system consisting genomic vector coding TLR5-receptor and its ligand 502s.<br>|
| Placebo Comparator: Placebo<br>Patients with histologically verified non-metastatic prostate cancer (stage 1 or 2) treated with Placebo (Glucose 5%) | Drug: Placebo<br>* 5% infusion solution of dextrose<br>* Other names: Glucose 5%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and intensity of adverse events (according to CTCAE v 4.03 classification) |  | Baseline to up to 29 days after the drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exposure of Mobilan DNA vector in patient's peripheral blood | Using validated PCR assay | Baseline to up to 29 days after the drug administration | 
| Prostate-specific antigen (PSA) measure | Baseline PSA level will be taken from medical history | 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 | 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. | On Day 29 after the drug administration | 
| Presence of protein 502s in blood plasma | Using ELISA assay | Baseline to up to 29 days after the drug administration | 
| Titer of 502 antibodies (AB) in peripheral blood serum | Using ELISA assay | 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 | On Day 29 after the drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate cancer, adenovirus, TLR5, immunotherapy