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RBL001/RBL002 Phase I Clinical Trial (MERIT)

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ClinicalTrials.gov Identifier: NCT01684241
Recruitment Status : Completed
First Posted : September 12, 2012
Last Update Posted : January 18, 2020
Information provided by (Responsible Party):
BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH )

Tracking Information
First Submitted Date  ICMJE September 10, 2012
First Posted Date  ICMJE September 12, 2012
Last Update Posted Date January 18, 2020
Study Start Date  ICMJE June 2012
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
Number of adverse events [ Time Frame: 90 days ]
Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2012)
  • Determination of antitumoral immune responses [ Time Frame: 90 days ]
    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 ]
    Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE RBL001/RBL002 Phase I Clinical Trial
Official Title  ICMJE 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
Brief Summary 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma
Intervention  ICMJE 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
Study Arms  ICMJE 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
Intervention: Biological: RBL001/RBL002
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 21, 2015)
Original Estimated Enrollment  ICMJE
 (submitted: September 10, 2012)
Actual Study Completion Date  ICMJE July 2015
Actual Primary Completion Date May 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Germany
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01684241
Other Study ID Numbers  ICMJE RB_0001-01
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party BioNTech SE ( BioNTech RNA Pharmaceuticals GmbH )
Original Responsible Party Ribological GmbH
Current Study Sponsor  ICMJE BioNTech RNA Pharmaceuticals GmbH
Original Study Sponsor  ICMJE Ribological GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ugur Sahin, Prof. Dr. Ribological GmbH
PRS Account BioNTech SE
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP