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    Summary
    EudraCT Number:2016-004727-23
    Sponsor's Protocol Code Number:3850
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-05-18
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2016-004727-23
    A.3Full title of the trial
    A Trial of Intra-pleuraL OK-432 Therapy in mesothelioma (TILT): A feasibility study using the ‘trial within a cohort’ methodology
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    TILT - a trial of a bacterial agent called OK432, administered directly into the chest via an indwelling catheter in people with cancer of the lung lining (mesothelioma).
    A.3.2Name or abbreviated title of the trial where available
    TILT
    A.4.1Sponsor's protocol code number3850
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNorth Bristol NHS Trust Research & Innovation
    B.1.3.4Country
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNational Institute of Health Research
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNorth Bristol NHS Trust
    B.5.2Functional name of contact pointResearch & Innovation
    B.5.3 Address:
    B.5.3.1Street AddressLearning and Research Building
    B.5.3.2Town/ cityBristol
    B.5.3.3Post codeBS10 5NB
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number0117 414 9329
    B.5.6E-mailresearchsponsor@nbt.nhs.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Picibanil
    D.2.1.1.2Name of the Marketing Authorisation holderChugai Pharmaceuticals
    D.2.1.2Country which granted the Marketing AuthorisationJapan
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePicibanil
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntrapleural use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOK432
    D.3.9.1CAS number 39325-01-4
    D.3.9.3Other descriptive namePicibanil
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit Other
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.8 to mg/KE
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product Yes
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Malignant pleural mesothelioma
    E.1.1.1Medical condition in easily understood language
    Cancer of the outside lining of the lung
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10059518
    E.1.2Term Pleural mesothelioma malignant
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The aim of this study is to answer the question “Is it possible (feasible) to undertake a trial within a cohort to investigate the effect of OK432, administered directly into the chest in people with mesothelioma, and is it acceptable to patients and relatives?”

    This research will determine whether a full-scale version of the trial is possible. If it is, the results of this research will inform the design of the subsequent full-scale trial.

    The long-term goal is to determine whether OK432 is an effective treatment for mesothelioma, and whether the trial within a cohort design is appropriate for mesothelioma trials.
    E.2.2Secondary objectives of the trial
    The secondary objective of this study is to gather preliminary (exploratory) information on the clinical effect of OK432 administered into the lung lining in people with mesothelioma. This information will be used to decide what the primary outcome measure of the subsequent full-scale trial should be. The results for the chosen outcome measure from this research will be used to calculate the sample size needed for the subsequent trial.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    To participate in TILT patients must meet all of the following inclusion criteria:
    • Histological or cytological diagnosis of mesothelioma
    • Enrolled in ASSESS-meso and has given consent to be considered for and be randomly selected for future trials
    • Indwelling pleural catheter (IPC) in situ that has drained more than 50ml of fluid on previous 3 drainages OR willing to have an IPC and has a pleural effusion suitable for IPC insertion
    • No chemotherapy in preceding 4 weeks and none planned in subsequent 4 weeks
    • Performance status ≤2, or PS 3 and felt clinically suitable for trial
    • Predicted survival ≥12 weeks from enrolment
    • Able to give written informed consent & meet trial requirements
    E.4Principal exclusion criteria
    To be eligible for TILT, participants must have none of the following exclusion criteria:
    • No indwelling pleural catheter (IPC) in situ, and has contra-indication to IPC insertion
    • Clinico-radiological diagnosis of mesothelioma
    • Trapped lung with <50% pleural apposition on x-ray
    • Moderately heavy or heavily loculated pleural effusion
    • Known immunodeficiency or immuno-suppressive medication
    • Intercurrent infection (pleural or elsewhere) or clinical signs of sepsis
    • Known sensitivity or allergy to OK432 or penicillin
    • Previous treatment with immunotherapy
    • Currently enrolled in any other interventional clinical trial
    • Brain metastases or CNS involvement of mesothelioma
    • Pregnancy or lactation, current or planned during the study period
    • Age <18
    • Any other factor that, in the opinion of the Chief Investigator, would mean participation in the study would be contraindicated
    E.5 End points
    E.5.1Primary end point(s)
    Feasibility.
    This assessment will be based on:
    • Screening, eligibility and recruitment rates to TILT
    • Feasibility of identifying 45 eligible participants in a 12 month period
    • Acceptance rates for intra-pleural OK-432 following random selection
    • Collection of data on participants who declined to receive OK-432 when offered it
    • Collection of data on participants within ASSESS-meso who declined to be considered for future trials
    • Attrition rates and data completeness rates
    • Acceptability of trial processes and design to participants and their relatives, assessed qualitatively.
    E.5.1.1Timepoint(s) of evaluation of this end point
    This will be evaluated at the end of trial - i.e. 12 weeks after the final participant has enrolled.
    E.5.2Secondary end point(s)
    Secondary outcome measures will collect exploratory data on the clinical efficacy of OK-432. This data will be used to decide the primary outcome for the subsequent full-scale trial, and to estimate the variance of the chosen outcome for a sample-size calculation. Potential outcomes include:

    • Tumour response, based on CT appearances
    • Overall survival (OS), defined as time between date of diagnosis with MPM to date of death, censored 12 weeks after the final trial visit of the final participant
    • Progression-free survival rates
    • Patient-reported chest pain and breathlessness, measured on visual analogue scales
    • Patient-reported quality of life, measured using the EQ-5D-5L health questionnaire
    • Pleurodesis rates, defined as pleural fluid drainage of less than 50ml on 3 consecutive occasions, with <25% opacification on CXR or <250ml pleural fluid on thoracic ultrasound scanning (TUS)
    • Time to pleurodesis, calculated from baseline assessment to date of pleurodesis
    • Biomarker response assessed using serial serum and pleural mesothelin levels.
    • Pleural fluid cytokine response, including VEG-F and TNF-α
    E.5.2.1Timepoint(s) of evaluation of this end point
    Tumour response will be assessed at baseline and 12 weeks
    Overall survival will be assessed at the end of trial (last visit of last participant)
    Progression free survival rates will be assessed at 12 weeks
    Patient reported outcomes and QoL will be assessed at baseline, week 2, week 5 and week 12
    Daily VAS scores will be collected for 21 days between week 2 and week 5
    Pleurodesis rates will be assessed at week 5 and week 12
    Biomarkers and pleural fluid cytokines will be measured at week 0, week 2, week 5 and week 12.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Feasibility
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Usual care
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 15
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state45
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 45
    F.4.2.2In the whole clinical trial 45
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Once the trial ends, participants will return to usual care.



    If this trial demonstrates feasibility, a full-scale, suitably-powered trial will be undertaken to assess whether OK432 has any clinical effectiveness in mesothelioma.

    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation N/A
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-06-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-06-19
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
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