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    Summary
    EudraCT Number:2015-003645-25
    Sponsor's Protocol Code Number:20110261
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2021-06-17
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2015-003645-25
    A.3Full title of the trial
    A Phase 1, Multi-center, Open-label, Dose De-escalation Study to Evaluate the Safety and Efficacy of Talimogene Laherparepvec in Pediatric Subjects with Advanced Non Central Nervous system tumors That are Amenable to Direct Injection
    Studio multicentrico, in aperto, di fase 1, di riduzione graduale della dose, per la valutazione della sicurezza e dell’efficacia di talimogene laherparepvec in soggetti pediatrici con tumori non-SNC avanzati adatti a iniezione diretta
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of talimogene laherparepvec in pediatric subjects with tumors that are able to be directly injected and do not occur in the spinal cord or brain.
    Uno studio con talimogene laherparepvec in soggetti pediatrici con tumori adatti ad una iniezione diretta che non sono a carico del midollo spinale o del cervello
    A.3.2Name or abbreviated title of the trial where available
    NA
    NA
    A.4.1Sponsor's protocol code number20110261
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/047/2013
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAMGEN INC.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAmgen Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen S.r.l
    B.5.2Functional name of contact pointMedical Information
    B.5.3 Address:
    B.5.3.1Street AddressVa Tazzoli 6
    B.5.3.2Town/ cityMilano
    B.5.3.3Post code20154
    B.5.3.4CountryItaly
    B.5.4Telephone number0039026241121
    B.5.5Fax number0039026241121
    B.5.6E-mailmedicalinformationitaly@amgen.com
    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 IMLYGIC
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V
    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 nameTalimogene Laherparepvec
    D.3.2Product code [AMG 678]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntralesional use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTalimogene laherparepvec
    D.3.9.1CAS number 1187560-31-1
    D.3.9.2Current sponsor codeAMG 678
    D.3.9.4EV Substance CodeSUB130338
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1000000
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    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 Yes
    D.3.11.3.5.1CAT classification and reference numberClassified as a Gene Therapy Medicinal Product EMA/CAT/451866/2012
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    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 IMLYGIC
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V
    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 nameTalimogene Laherparepvec
    D.3.2Product code [AMG 678]
    D.3.4Pharmaceutical form Concentrate for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntralesional use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTalimogene laherparepvec
    D.3.9.1CAS number 1187560-31-1
    D.3.9.2Current sponsor codeAMG 678
    D.3.9.3Other descriptive nameTALIMOGENE LAHERPAREPVEC
    D.3.9.4EV Substance CodeSUB130338
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100000000
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product Yes
    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 Yes
    D.3.11.3.5.1CAT classification and reference numberClassified as a Gene Therapy Medicinal Product EMA/CAT/451866/2012
    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) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Non-Central Nervous System (CNS) Tumors
    Tumori del sistema nervoso non centrale (CNS)
    E.1.1.1Medical condition in easily understood language
    Tumors that can be injected and do not occur in the brain or spinal cord
    Tumori che possono essere iniettati e non si verificano nel cervello o nel midollo spinale
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the safety and tolerability of talimogene laherparepvec, as assessed by incidence of dose-limiting toxicities (DLT), in pediatric subjects with advanced non-central nervous system (CNS) tumors that are amenable to direct injection.
    Determinare la sicurezza e la tollerabilità di talimogene laherparepvec, in termini di incidenza di tossicità dose-limitante (DLT), in soggetti pediatrici con tumori non-SNC avanzati adatti a iniezione diretta.
    E.2.2Secondary objectives of the trial
    • To evaluate the anti-tumor activity of talimogene laherparepvec, as assessed by overall response rate (ORR), duration of response (DOR), time to response (TTR), time to progression (TTP), progression-free survival (PFS) using immune-related response criteria simulating Response Evaluation Criteria in Solid Tumor (RECIST 1.1) (modified Immune-related Response Criteria Simulating Response Evaluation Criteria in Solid Tumors [irRC-RECIST]), and overall survival (OS).
    •Valutare l’attività antitumorale di talimogene laherparepvec, in termini di tasso di risposta globale (ORR), durata della risposta (DOR), tempo alla risposta (TTR), tempo alla progressione (TTP), sopravvivenza libera da progressione (PFS), utilizzando i criteri di valutazione della risposta immunocorrelati che simulano i criteri di valutazione della risposta nei tumori solidi (RECIST 1.1) (criteri di valutazione della risposta immunocorrelati modificati che simulano i criteri di valutazione della risposta nei tumori solidi [irRC-RECIST]), e sopravvivenza globale (OS).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Subjects must be 2 to = 21 years of age at the time of informed consent/assent.
    • Subjects must have local HSV-1 serostatus with measurable or nonmeasurable disease.
    • Subject must have histologically or cytologically confirmed non-CNS solid tumor that recurred after standard/frontline therapy (or for which there is no standard/frontline therapy available).
    • The subject must be a candidate for intralesional therapy and have Karnofsky performance status of = 70% for subjects 12 to = 21 years of age or Lansky play scale of = 70% for children 2 to < 12 years of age.
    • Subjects must have a life expectancy of > 4 months from date of enrollment and adequate organ function.
    • Female subjects of childbearing potential must have a negative
    • I soggetti devono avere un'età compresa tra 2 e = 21 anni al momento del consenso / assenso informato.
    • I soggetti devono avere un sierostato HSV-1 locale con malattia misurabile o non misurabile.
    • Il soggetto deve avere un tumore solido non CNS istologicamente o citologicamente confermato che si sia ripresentato dopo terapia standard / frontale (o per il quale non esiste una terapia standard / di prima linea disponibile).
    • Il soggetto deve essere un candidato per la terapia intralesionale e avere uno stato di prestazione di Karnofsky = 70% per soggetti di età compresa tra 12 e = 21 anni o una scala di riproduzione di Lansky = 70% per bambini da 2 a <12 anni di età.
    • I soggetti devono avere un'aspettativa di vita> 4 mesi dalla data di arruolamento e una funzione organica adeguata.
    • Le donne in età fertile devono avere un esito negativo
    E.4Principal exclusion criteria
    • Diagnosis of leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, or other hematologic malignancy
    • Radiotherapy to the bone marrow within a period of time (see definition in protocol)
    • Primary ocular or mucosal melanoma
    • History of other malignancy within the past 5 years (see protocol for exception
    • History or evidence of active autoimmune disease that requires systemic treatment (see protocol for description)
    • Active herpetic skin lesions or prior complications of herpetic infection
    • Prior treatment with talimogene laherparepvec or any other oncolytic virus or with a tumor vaccine
    • Requires intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use

    Please refer to protocol for the full list
    • Diagnosi di leucemia, linfoma non-Hodgkin, malattia di Hodgkin o altra neoplasia ematologica
    • Radioterapia al midollo osseo entro un periodo di tempo (vedi definizione nel protocollo)
    • Melanoma primitivo oculare o mucosale
    • Storia di altre neoplasie negli ultimi 5 anni (vedi protocollo per eccezione)
    • Storia o evidenza di malattia autoimmune attiva che richiede trattamento sistemico (vedi protocollo per la descrizione)
    • Lesioni erpetiche cutanee attive o complicanze pregresse di infezione erpetica
    • Trattamento precedente con talimogene laherparepvec o qualsiasi altro virus oncolitico o con un vaccino tumorale
    • Richiede un trattamento intermittente o cronico con un farmaco antiherpetico (ad es. aciclovir), oltre all'uso intermittente per uso topico

    Fare riferimento al protocollo per la lista completa
    E.5 End points
    E.5.1Primary end point(s)
    Subject incidence of DLTs
    Incidenza per soggetto di DLT
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary analysis will occur 35 days after the last subject has enrolled and received at least 1 dose of talimogene laherparepvec.
    L'analisi primaria avverrà 35 giorni dopo che l'ultimo soggetto si è iscritto e ha ricevuto almeno 1 dose di talimogeno laherparepvec.
    E.5.2Secondary end point(s)
    ORR, DOR, TTR, TTP, PFS, and OS will be summarized in the overall population
    RR, DOR, TTR, TTP, PFS e OS saranno riepilogati nel complesso popolazione
    E.5.2.1Timepoint(s) of evaluation of this end point
    Asessed during the Primary Analysis and updated during the Final Analysis
    Valutato durante l'analisi primaria e aggiornato durante l'analisi finale
    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 Yes
    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 No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Dose De-Escalation
    Dose De-Escalation
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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 No
    E.8.2.4Number of treatment arms in the trial6
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Canada
    United States
    Belgium
    France
    Italy
    Spain
    Sweden
    Switzerland
    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
    The time when the last subject is assessed or receives an intervention for evaluation in the study. The end of study will occur when the last subject discontinues talimogene laherparepvec and has had the opportunity to complete both the safety follow-up visit and the longterm follow-up.
    momento in cui viene valutato l'ultimo soggetto o riceve un intervento per la valutazione nello studio. La fine dello studio si verificherà quando l'ultimo soggetto interrompe talimogene laherparepvec e ha avuto l'opportunità di completare sia la visita di controllo sulla sicurezza che il follow-up a lungo termine.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months11
    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 Yes
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 3
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 6
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Inclusion criteria includes that subject's legally acceptable representative can provide informed consent/assent when the subject is legally too young to provide informed consent/assent and the subject has provided written assent
    I criteri di inclusione includono il rappresentante legalmente accettabile di quel soggetto in grado di fornire consenso / consenso informato quando il soggetto è legalmente troppo giovane per fornire consenso informato / assenso e l'argomento ha for
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 13
    F.4.2.2In the whole clinical trial 24
    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)
    none
    nessuno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-04-29
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-04-10
    P. End of Trial
    P.End of Trial StatusCompleted
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