Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36092   clinical trials with a EudraCT protocol, of which   5933   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2013-005552-15
    Sponsor's Protocol Code Number:20120325
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2015-07-09
    Trial 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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2013-005552-15
    A.3Full title of the trial
    A Phase 2, Multicenter, Open-label, Single-arm Trial to Evaluate the Correlation Between Objective Response Rate and Baseline Immunoprofile Intratumoral CD8+ Cell Density in Subjects With Unresected Stage IIIB to IVM1c Melanoma Treated with Talimogene Laherparepvec
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase 2 biomarker study evaluating subjects with unresected, advanced melanoma treated with talimogene laherparepvec
    A.4.1Sponsor's protocol code number20120325
    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 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 (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ medical Info-Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post codeCH-6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@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 No
    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 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.3.9.2Current 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 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 No
    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 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.3.9.2Current 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
    Unresected stage IIIB to IVM1c melanoma
    E.1.1.1Medical condition in easily understood language
    Melanoma
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To explore the correlation between a baseline immunoprofile (ie, intratumoral CD8+ cell density) and objective response rate (ORR) in subjects with unresected stage IIIB to IVM1c melanoma treated with talimogene laherparepvec.
    E.2.2Secondary objectives of the trial
    - to explore the correlation between a baseline immunoprofile (ie, intratumoral CD8+ cell density) and durable response rate (DRR), duration of response (DOR), and changes in tumor burden
    - to explore the correlation between changes in an immunoprofile intratumoral CD8+ cell density during treatment (in injected and uninjected lesions) and ORR, DRR, DOR, and changes in tumor burden
    - to evaluate ORR, DOR, time to treatment failure (TTF), DRR, OS, and change in tumor burden during treatment
    - to evaluate the safety and tolerability of talimogene laherparepvec
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Subject has provided informed consent prior to initiation of any study-specific activities/procedures
    - Male or female age ≥ 18 years at the time of informed consent
    - Histologically confirmed diagnosis of melanoma
    - Subject with unresected stage IIIB to IVM1c melanoma for whom surgery is not recommended
    - Subject who is treatment naïve: must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IVM1c melanoma
    - subjects who received prior adjuvant therapy for melanoma may be eligible as long as prior adjuvant therapy was completed at least 6 months prior to enrollment
    - Candidate for intralesional therapy (ie, disease is appropriate for direct injection or through the use of ultrasound guidance) defined as one of the following:
    -at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion ≥ 10 mm in longest diameter, or
    - multiple injectable melanoma lesions that in aggregate have a longest diameter of ≥ 10 mm
    - Measurable disease defined as one or more of the following:
    - at least 1 melanoma lesion that can be accurately and serially measured in at least 2 dimensions and for which the greatest diameter is ≥ 10 mm as measured by contrast-enhanced or spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or ultrasound for nodal/soft tissue disease (including lymph nodes)
    - at least 1 ≥ 10 mm superficial cutaneous or subcutaneous melanoma lesion as measured by calipers
    - multiple superficial melanoma lesions which in aggregate have a total diameter of ≥ 10 mm
    - Serum lactate dehydrogenase (LDH) levels ≤ 1.5 X upper limit of normal (ULN) within 28 days prior to enrollment
    - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix E)
    - Adequate organ function determined within 28 days prior to enrollment, defined as follows:
    - absolute neutrophil count ≥ 1500/mm3
    - platelet count ≥ 75,000/mm3
    - hemoglobin ≥ 8 g/dL without need for hematopoietic growth factor or transfusion support
    - serum creatinine ≤ 1.5 x ULN
    - serum bilirubin ≤ 1.5 x ULN
    - aspartate amino transferase (AST) ≤ 2.5 x ULN
    - alanine amino transferase (ALT) ≤ 2.5 x ULN
    - alkaline phosphatase ≤ 2.5 x ULN
    - serum albumin ≥ 2.5 g/dL
    - prothrombin time (PT) ≤ 1.5 x ULN (or international normalization ratio [INR] ≤ 1.3)*
    - partial thromboplastin time (PTT) ≤ 1.5 x ULN
    E.4Principal exclusion criteria
    - Clinically active cerebral metastases. Subjects with up to 3 (neurological performance status of 0) cerebral metastases may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy (including Gamma Knife) or craniotomy, with no evidence of progression and have not required steroids for at least two months prior to enrollment.
    - Greater than 3 visceral metastases (this does not include lung metastases or nodal metastases associated with visceral organs). For subjects with 3 visceral metastases, no lesion > 3 cm and liver lesions must be stable for at least 1 month prior to enrollment.
    - Bone metastases
    - Primary ocular or mucosal melanoma
    - History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease
    - Evidence of clinically significant immunosuppression such as the following:
    - primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
    - concurrent opportunistic infection
    - receiving systemic immunosuppressive therapy (> 2 weeks), including oral steroid doses > 10 mg/day of prednisone or equivalent
    - Active herpetic skin lesions or prior complications of HSV-1 infection (eg, herpetic keratitis or encephalitis)
    - Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use
    - Previous treatment with talimogene laherparepvec
    - Any nononcology vaccine therapies used for the prevention of infectious disease within 28 days prior to enrollment and during treatment period
    - Currently receiving treatment with another investigational device or drug study, or less than 28 days since ending treatment with another investigational device or drug study(s)
    - Other investigational procedures while participating in this study are excluded
    - Known to have acute or chronic active hepatitis B infection
    - Known to have acute or chronic active hepatitis C infection
    - Known to have human immunodeficiency virus infection
    - History of other malignancy within the past 3 years with the following exceptions:
    - malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
    - adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
    - adequately treated cervical carcinoma in situ without evidence of disease
    - adequately treated breast ductal carcinoma in situ without evidence of disease
    -prostatic intraepithelial neoplasia without evidence of prostate cancer
    - adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
    - Subject has known sensitivity to any of the products or components to be administered during dosing
    - Subject likely to not be available to complete all protocol required study visits or procedures, and/or to comply with all required study procedures to the best of the subject’s and investigator’s knowledge
    - History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
    - Subject previously has entered this study
    - Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of talimogene laherparepvec
    - Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint of the study is the correlation between baseline intratumoral CD8+ cell density and objective response rate (ORR).
    E.5.1.1Timepoint(s) of evaluation of this end point
    The timing of the primary analysis will be when all subjects have had the opportunity to complete 12 months of treatment of talimogene laherparepvec.
    E.5.2Secondary end point(s)
    Multiple biomarkers will be examined to assess the correlation between their baseline value and DRR, DOR, and changes in tumor burden as well as the changes in their value during treatment with ORR, DRR, DOR, changes in tumor burden.
    Subject incidence rates of treatment-emergent adverse events (including all adverse events, grade ≥ 3 adverse events, serious adverse events, adverse events of interest and events requiring the discontinuation of study drug,and local effects on the tumor [ie, pain, inflammation and ulceration]) will be summarized.
    Clinically significant laboratory changes and clinically significant changes in vital signs will be summarized with descriptive statistics. Summary statistics will also be provided for concomitant medications, dose delay, study drug discontinuation, overall exposure, and changes in ECOG performance status.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The timing of the primary analysis will be when all subjects have had the opportunity to complete 12 months of treatment of talimogene laherparepvec.
    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 No
    E.6.5Efficacy No
    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 No
    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 No
    E.8.1.1Randomised No
    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 No
    E.8.2.4Number of treatment arms in the trial1
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA49
    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
    The end of study will occur when the last subject discontinues talimogene laherparepvec and has had the opportunity to complete the safety follow-up visit or the last long term follow-up visit, whichever occurs later
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    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 years3
    E.8.9.2In all countries concerned by the trial months7
    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.1.1.1In 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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 110
    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
    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 Decision2015-06-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-28
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2019 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA