Ignite Creation Date:
2025-12-24 @ 11:38 PM
Ignite Modification Date:
2026-01-02 @ 11:29 AM
Study NCT ID:
NCT02035956
Status:
COMPLETED
Last Update Posted:
2020-01-18
First Post:
2014-01-10
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
IVAC MUTANOME Phase I Clinical Trial
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008545', 'term': 'Melanoma'}], 'ancestors': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D019496', 'term': 'Cancer Vaccines'}], 'ancestors': [{'id': 'D014612', 'term': 'Vaccines'}, {'id': 'D001688', 'term': 'Biological Products'}, {'id': 'D045424', 'term': 'Complex Mixtures'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 15}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-01', 'completionDateStruct': {'date': '2019-10', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-01-14', 'studyFirstSubmitDate': '2014-01-10', 'studyFirstSubmitQcDate': '2014-01-13', 'lastUpdatePostDateStruct': {'date': '2020-01-18', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-01-14', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-02-14', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and tolerability of repetitive doses', 'timeFrame': 'up to a maximum of 189 days', 'description': 'Number of Patients with adverse events, total number of adverse events'}], 'secondaryOutcomes': [{'measure': 'Monitoring of vaccine-induced cellular immune response,', 'timeFrame': '161 days', 'description': 'Determination of pharmacodynamic activity'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['IVAC MUTANOME', 'IVAC', 'personalized therapy', 'personalized immuno therapy', 'RB_0004-01', 'Ribological', 'Melanoma', 'cancer vaccine'], 'conditions': ['Melanoma']}, 'referencesModule': {'references': [{'pmid': '35379963', 'type': 'DERIVED', 'citation': 'Weber D, Ibn-Salem J, Sorn P, Suchan M, Holtstrater C, Lahrmann U, Vogler I, Schmoldt K, Lang F, Schrors B, Lower M, Sahin U. Accurate detection of tumor-specific gene fusions reveals strongly immunogenic personal neo-antigens. Nat Biotechnol. 2022 Aug;40(8):1276-1284. doi: 10.1038/s41587-022-01247-9. Epub 2022 Apr 4.'}]}, 'descriptionModule': {'briefSummary': 'Clinical first-in-human study evaluating the safety, tolerability and immunogenicity of intra-nodal administration of a personalized vaccination with IVAC MUTANOME vaccine with or without initial treatment with RBL001/RBL002 vaccine in patients with advanced melanoma', 'detailedDescription': "IVAC MUTANOME is a poly-neo-epitopic coding RNA vaccine targeting the unique mutation signature of an individual patient. It is engineered on demand, provided as two patient-specific RNA drug products and administered as an individual treatment.\n\nRBL001/RBL002 and IVAC MUTANOME are naked ribonucleic acid (RNA) based recombinant vaccines optimized to induce antigen-specific CD8+ and CD4+ T cell responses against melanoma associated target antigens.\n\nThe two antigens are well characterized antigens in melanoma that have been previously utilized with excellent safety and proven immunogenicity as vaccine targets in a number of independent clinical trials.\n\nThe overall rationale of the study is to determine safety of the novel RNA-based vaccine strategy and determine the number and function of vaccine-induced antigen-specific immune-responses as early biomarkers for the clinical mode of action.\n\nThe IVAC MUTANOME vaccine approach is based on targeting multiple immunogenic tumour mutations unique to a given patient's tumour using a poly-epitopic RNA-based vaccine manufactured for use in a single patient only. Parallel to the target discovery process and on demand manufacturing of IVAC MUTANOME vaccine patients with RBL001 and/ or RBL002 positive-tumours will receive the RBL001/RBL002 vaccine. Patients which tumours that are RBL001 and RBL002 negative can also be included into the clinical study but will not receive RBL001/RBL002 prior to IVAC MUTANOME. Applying this approach the RBL001/RBL002 vaccine and the IVAC MUTANOME vaccine administration is expected to lead to several effects contributing to their immunological (therapeutic) effects."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Malignant Melanoma, resectable stage IIIA-C and IV (AJCC 2009 melanoma classification)\n* Patients with unresectable Malignant Melanoma stage IIIA-C in complete remission, partial remission or stable disease after treatment with vemurafenib or patients with slow progressive disease.\n* Malignant Melanoma, unresectable stage IV (AJCC 2009 melanoma classification) in complete remission, partial remission or stable disease after treatment with vemurafenib\n* All lines of treatment for malignant melanoma are accepted.\n* First line therapy for subjects not eligible or declining other first line therapies after all available treatment options have been transparently disclosed (to be documented in patient medical record).\n* ≥ 18 years of age\n* Written informed consent\n* ECOG performance status (PS) 0-1 (appendix G)\n* Life expectancy \\> 6 months\n* WBC ≥ 3x109/L\n* Haemoglobin ≥ 10 g/dl\n* Platelet count ≥ 100,000/mm³\n* LDH level \\< 2.0 x ULN\n* Negative pregnancy test (measured by β-HCG) for females which are childbearing potential\n* Suitable lymph nodes for injection using ultrasound guidance\n\nExclusion Criteria:\n\n* Pregnancy or breastfeeding\n* Primary ocular melanoma\n* History (\\< 5 years) of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer or cervical carcinoma in situ\n* Brain metastases\n* Known or symptomatic pleural effusions and/or ascites\n* Known hypersensitivity to the active substance or to any of the excipients\n* A serious local infection (e.g. cellulitis, abscess) or systemic infection (e.g. pneumonia, septicemia) which requires systemic antibiotic treatment within 2 weeks prior to the first dose of study medication\n* Positive test for acute or chronic active hepatitis B or C infection, acute EBV or acute CMV injection\n* Clinically relevant autoimmune disease\n* Systemic immune suppression:\n* HIV disease\n* Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted)\n* Other clinical relevant systemic immune suppression\n* Symptomatic congestive heart failure (NYHA 3 or 4)\n* Unstable angina pectoris\n* Radiotherapy within two weeks, myelosuppressive chemotherapy, ipilimumab and major surgery within 4 weeks/28 days before the first treatment. Interferon and approved BRAF inhibitors will be allowed as concurrent treatment.\n* Any investigational drug within 4 weeks/28 days or 5 half-lives depending on what gives the longer range before the first treatment of this study\n* Minor surgery within 14 days before the first treatment of this study\n* Fertile males and females who are unwilling to use a highly effective method of birth control (less than 1% per year, e.g. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches or intrauterine device) during study treatment and 28 days after the last dose of study treatment\n* Presence of a serious concurrent illness or other condition (e.g. psychological, family, sociological, or geographical circumstances) that does not permit adequate follow-up and compliance with the protocol'}, 'identificationModule': {'nctId': 'NCT02035956', 'briefTitle': 'IVAC MUTANOME Phase I Clinical Trial', 'organization': {'class': 'INDUSTRY', 'fullName': 'BioNTech SE'}, 'officialTitle': 'First-in-human Study Evaluating the Safety, Tolerability and Immunogenicity of i.n. Administration of a Personalized Vaccination With IVAC MUTANOME Vaccine w/o Initial Treatment With RBL001/RBL002 Vaccine in Patients With Advanced Melanoma', 'orgStudyIdInfo': {'id': 'RB_0004-01'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'IVAC MUTANOME RBL001/RBL002', 'description': 'All participants will be treated with the personalized IVAC MUTANOME vaccine with or without prior treatment with RBL001/RBL002 vaccine depending on expression of these two antigens. Vaccines will be administered intra-nodally.', 'interventionNames': ['Biological: IVAC MUTANOME, RBL001/RBL002']}], 'interventions': [{'name': 'IVAC MUTANOME, RBL001/RBL002', 'type': 'BIOLOGICAL', 'otherNames': ['cancer vaccine'], 'description': 'Each patient will receive multiple repeated intranodal injections of IVAC MUTANOME vaccine with or without initial treatment with RBL001/RBL002.', 'armGroupLabels': ['IVAC MUTANOME RBL001/RBL002']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1090', 'city': 'Vienna', 'state': 'AT-Wien', 'country': 'Austria', 'facility': 'Medizinische Universität Wien', 'geoPoint': {'lat': 48.20849, 'lon': 16.37208}}, {'zip': '55131', 'city': 'Mainz', 'country': 'Germany', 'facility': 'Hautklinik und Poliklinik Universitätsmedizin der Johannes-Gutenberg Universität Mainz', 'geoPoint': {'lat': 49.98185, 'lon': 8.28008}}, {'zip': '68167', 'city': 'Mannheim', 'country': 'Germany', 'facility': 'Klinik für Dermatologie, Venerologie und Allergologie UMM - Universitätsmedizin Mannheim Medizinische Fakultät Mannheim der Ruprecht-Karls-Universität Heidelberg', 'geoPoint': {'lat': 49.4891, 'lon': 8.46694}}], 'overallOfficials': [{'name': 'Ugur Sahin, Prof. Dr.', 'role': 'STUDY_DIRECTOR', 'affiliation': 'BioNTech RNA Pharmaceuticals GmbH'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'BioNTech RNA Pharmaceuticals GmbH', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}