RBL001/RBL002 Phase I Clinical Trial (MERIT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Biontech RNA Pharmaceuticals GmbH
Sponsor:
Collaborator:
on 01.03.2014 Ribological GmbH renamed to Biontech RNA Pharmaceuticals GmbH
Information provided by (Responsible Party):
Biontech RNA Pharmaceuticals GmbH
ClinicalTrials.gov Identifier:
NCT01684241
First received: September 10, 2012
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

Clinical first-in-human dose escalation study evaluating the safety and tolerability of intranodal administration of an RNA-based cancer vaccine targeting two tumor-associated antigens in patients with advanced melanoma


Condition Intervention Phase
Melanoma
Biological: RBL001/RBL002
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Clinical First-in-human Dose Escalation Study Evaluating the Safety and Tolerability of Intranodal Administration of an RNA-based Cancer Vaccine Targeting Two Tumor-associated Antigens in Patients With Advanced Melanoma

Resource links provided by NLM:


Further study details as provided by Biontech RNA Pharmaceuticals GmbH:

Primary Outcome Measures:
  • Number of adverse events [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]
    Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities


Secondary Outcome Measures:
  • Determination of antitumoral immune responses [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Cellular immune responses, cytokines, AB responses, serum biomarkers, and further immunological parameters will be determined once or repeatedly in the course of treatment. In the latter case changes from baseline will be tabulated.

  • Clinical Monitoring of Tumor Lesions [ Time Frame: 90 days ] [ Designated as safety issue: No ]
    Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.


Estimated Enrollment: 21
Study Start Date: June 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RBL001/RBL002 intranodal administration

All participants will be treated with RBL001/RBL002 after allocation to one of the four escalating dose cohorts:

  • Cohort-1 50 µg RBL001 and 50 µg RBL002
  • Cohort-2 100 µg RBL001 and 100 µg RBL002
  • Cohort-3 300 µg RBL001 and 300 µg RBL002
  • Cohort-4 600 µg RBL001 and 600 µg RBL002
Biological: RBL001/RBL002
Each participant will receive 8 repeated intranodal administrations of RBL001 and RBL002 during a time frame of 43 to 51 days.
Other Name: cancer vaccine

Detailed Description:

RBL001/RBL002 are naked ribonucleic acid (RNA) based recombinant vaccines that were optimized to induce antigen specific CD8+ and CD4+ T cell responses against malignant melanoma target antigens.

The Targeted 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.

The overall rationale of the study is to determine safety of the novel RNA based vaccine approach and determine vaccine target antigen directed immune responses as early biomarkers for clinical mode of action.

The RBL001/RBL002 vaccine is expected to lead to several effects contributing to its immunological (therapeutic) effect. First, ultrasound guided administration of naked RNA drug product into lymph nodes is expected to result in rapid uptake of naked RNA by lymph node resident professional antigen-presenting cells (APCs). Incorporated RNA is known to translocate to the cytoplasm leading to its translation by the host ribosome complex into the respective protein antigens. The recombinant vaccine is optimized for immunogenicity and enables presentation of diverse antigenic epitopes on both HLA-class I as well as HLA-class II molecules. Consecutively, antigen-specific CD8+ and CD4+ T cell responses will be triggered by HLA-peptide complexes on the surface of antigen presenting cells. In addition, RNA administration will also lead to transient activation (change of surface marker expression and cytokine secretion) of APCs in the targeted lymph nodes particularly via signaling of TLR 7 and 8 leading to an adjuvant effect, supporting the induction of target-specific T cell responses with systemic anti-tumor activity.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stage IIC, IIIA-C or unresectable stage IV of cutaneous melanoma (AJCC 2009 melanoma classification)
  • 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!)
  • Antigen expression confirmed by RT-PCR analysis from FFPE
  • ≥ 18 years of age
  • Written informed consent (part I and part II)
  • ECOG performance status (PS) 0-1 or Karnofsky Index 70-100 %
  • Life expectancy > 3 months
  • WBC ≥ 3x109/L
  • Hemoglobin ≥ 10 g/dl
  • Platelet count ≥ 100,000/mm³
  • LDH level < 2.0 x ULN
  • Negative pregnancy test (measured by β-HCG) for females of childbearing age
  • Suitable lymph nodes for injection using ultrasound guidance

Exclusion Criteria:

  • Pregnancy or breastfeeding
  • Primary ocular melanoma
  • Presence of history (< 5 years) of a second malignancy other than squamous or basal cell carcinoma, non-active prostate cancer or cervical carcinoma in situ
  • Brain metastases
  • Known or symptomatic pleural effusions and/or ascites
  • Known hypersensitivity to the active substance or to any of the excipients
  • 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
  • Acute or chronic active hepatitis B or C infection, EBV or CMV
  • Receipt of allogenic stem cell transplantation
  • Clinically relevant autoimmune disease
  • Systemic immune suppression:
  • HIV disease
  • Use of chronic oral or systemic steroid medication (topical or inhalational steroids are permitted) Other clinical relevant systemic immune suppression
  • Symptomatic congestive heart failure (NYHA 3 or 4)
  • Unstable angina pectoris
  • Radiotherapy, chemotherapy, major surgery, immunotherapy, vaccination, any other concurrent anticancer therapy or any investigational drug within 28 days before the first treatment of this study
  • Minor surgery within 14 days before the first treatment of this study
  • Treatment with Ipilimumab within 84 days before the first treatment of this study
  • Fertile males and females who are unwilling to employ adequate means of contraception (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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684241

Contacts
Contact: Alexandra Kemmer-Brueck +49 6131 63580 ext 0 Alexandra.Kemmer-Brueck@biontech.de
Contact: Cedrik M Britten, Dr. +49 6131 63580 ext 0 Cedrik.Britten@biontechrna.de

Locations
Austria
Medizinische Universität Wien, Abteilung für Dermatologie Recruiting
Vienna, Austria, A-1090
Contact: Christoph Hoeller, Prof. Dr.         
Principal Investigator: Christoph Höller, Prof. Dr.         
Germany
Medizinische Fakultät der Universität Duisburg-Essen Recruiting
Essen, Germany, 45122
Contact: Dirk Schadendorf, Prof. Dr.         
Principal Investigator: Dirk Schadendorf, Prof. Dr.         
Universtitätsmedizin der Johannes-Gutenberg Universtität Recruiting
Mainz, Germany, 55131
Contact: Carmen Loquai, Dr.         
Principal Investigator: Carmen Loquai, PD Dr.         
Universitätsklinik Mannheim Recruiting
Mannheim, Germany
Contact: Jochen Utikal, Prof. Dr.         
Principal Investigator: Jochen Utikal, Prof. Dr.         
Sponsors and Collaborators
Biontech RNA Pharmaceuticals GmbH
on 01.03.2014 Ribological GmbH renamed to Biontech RNA Pharmaceuticals GmbH
Investigators
Study Director: Ugur Sahin, Prof. Dr. Biontech RNA Pharmaceuticals GmbH
  More Information

No publications provided

Responsible Party: Biontech RNA Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT01684241     History of Changes
Other Study ID Numbers: RB_0001-01
Study First Received: September 10, 2012
Last Updated: March 14, 2014
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by Biontech RNA Pharmaceuticals GmbH:
Biontech
Biontech RNA Pharmaceuticals GmbH
Biontech RNA
MERIT
RNA
Immuno Therapy
RB_0001-01
Ribological
Melanoma
RBL001
RBL002
cancer vaccine

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on July 22, 2014