1716-12

Virttu Biologics Limited

BioCity Scotland, Bo'Ness Road, Newhouse, United Kingdom, ML1 5UH

Clinical Trial Department, Virttu Biologics Limited, 0141 4451716,

Clinical Trial Laboratory, Virttu Biologics Limited, 0141 4451716,

No

No

No

Final

27 Jun 2017

Yes

14 Nov 2016

Yes

14 Nov 2016

No

The primary objective of the study was to determine the safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma. The secondary objective was to obtain evidence of HSV1716 replication and lysis of MPM cells and of patient immune responses through analysis of pleural fluid and serum samples for evidence of cell death, HSV1716 replication, changes in appropriate biomarkers and cytokine/chemokines. A subsidiary endpoint was tumour measurement as recorded by CT scans and assessed using the modified RECIST criteria for MPM.

Only patients who met the inclusion and exclusion criteria for the study were enrolled. These patients received a patient information leaflet that explained the procedures and any risks that may be involved. The patients were allowed at least 24 hours to read the information and ask any questions before consenting to the study. The safety and tolerability of HSV1716 was assessed at various time points during the study by review of pre- and post-dose clinical data including: physical examinations, full blood count, biochemical profile (urea, electrolytes, liver function tests, bilirubin, AST/ALT, serum creatinine, LDH, alkaline phosphatase, albumin, calcium) and immunological status. Reviews of this data were carried out two weeks after each patients' final dose and recruitment of another patient was based on whether or not any dose limiting toxicities were experienced. The administration procedure was designed to utilise the patients' indwelling catheters and this was done during an outpatient appointment at a time convenient to the patient.

21 Jan 2013

No

No

United Kingdom: 13

13

13

0

0

0

0

0

0

2

11

0

Overall trial (overall period)

Not applicable

HSV1716

Herpes simplex virus lacking infected cell protein 34.5, Seprehvir

Solution for injection

Intrapleural use

Patients received 1, 2 or 4 doses of 1x10^7 infectious units (iu) HSV1716 at weekly intervals, followed by a 50ml saline flush, by intrapleural administration via an Indwelling Pleural Catheter. The investigational product was provided in glass vials each containing approximately 1.2 ml of compound sodium lactate and 10% glycerol in which HSV1716 was diluted at a concentration of 2 x 10^6 iu/ml. Five vials were used for each dose and a total of 5ml drawn from the vials and administered to provide each dose of 1x10^7iu of HSV1716.

Overall trial

Completed study visits

This set of patients completed all study treatments and follow-up visits.

HSV1716 treatment

Completed study visits

This set of patients completed all study treatments and follow-up visits.

The primary objective of the study was to determine the safety and tolerability of HSV1716 given by single and repeat intrapleural administration in patients with inoperable malignant pleural mesothelioma. Safety results: • No ‘Dose Limiting Toxicities’ or other issues were identified and in all cases, it was concluded that recruitment could proceed to the higher dose level or in the case of Part B Group 2, recruitment could be expanded to include an additional three patients in the 4 dose cohort. • One ‘Serious Adverse Event’ reported (pleural infection) which was determined to be unlikely related to HSV1716.

Primary

Patients were evaluated for safety and tolerability of the procedure from the day of the first administration of HSV1716 through to the end of the 4th week from their final administration of HSV1716.

The secondary objective was to obtain evidence of HSV1716 replication and lysis of MPM cells through analysis of pleural fluid and serum samples for evidence of cell death and/or HSV1716 replication and/or changes in appropriate biomarkers. Biological results: • 11/12 patients were seropositive for HSV-1 pre-treatment, whereas 1 patient was seronegative and seroconverted • In 7/9 patients with detectable HSV DNA in pleural fluid samples, HSV-1 genomes were persistent for ≥ 14 days after the final administration, consistent with replication in tumour cells • Viral shedding was observed in 1/12 patients, no genotyping was performed to confirm whether this was HSV1716 • In 9/12 patients strong virus neutralisation by pleural fluid was observed • Pleural fluid levels of the cytokines IL-2, TNFalpha and IFNgamma increased after HSV1716 administration by 5-10-fold, and robust Th1 responses of these 3 cytokines to HSV1716 administration were observed in 8/11 patients

Secondary

Patient samples were assessed for biological activity from the day of the first administration of HSV1716 through to the last study visit.

A subsidiary endpoint was tumour measurement as recorded by CT scans and assessed using the modified RECIST criteria for MPM. Response assessment results: • Tumour response was obtained by CT scanning (screening, day 29 and day 57) using the modified RECIST criteria developed for malignant mesothelioma. Six patients were reported as having stable disease and 6 were reported as having progressive disease at day 57.

Other pre-specified

Tumour measurements were obtained and assessed at screening, day 29 and day 57.

Adverse events were reported from the time of consent to the final study visit.

Listing includes all Serious Adverse Events (1 unlikely related). Listing includes only those non-serious adverse events that were possibly or probably related to the investigational product. Additional non-serious adverse events were reported but were deemed to be unlikely or not related to the investigational product.

15

HSV1716 treatment arm