MelanomaPhase 1MERITNCT01684241
RBL001/RBL002 Phase I Clinical Trial
A Phase 1 study testing RBL001/RBL002 in people with Melanoma, run by BioNTech RNA Pharmaceuticals GmbH at 4 sites in 2 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- RBL001/RBL002
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jun 2012to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 %
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Germany3 sites
Medizinische Fakultät der Universität Duisburg-Essen
Essen, 45122
Universtitätsmedizin der Johannes-Gutenberg Universtität
Mainz, 55131
Universitätsklinik Mannheim
Mannheim
Austria1 site
Medizinische Universität Wien, Abteilung für Dermatologie
Vienna, A-1090
About this study
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
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
Read the 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.
- Conditions
- Melanoma
- Being tested
- RBL001/RBL002
- Keywords
- Biontech, Biontech RNA Pharmaceuticals GmbH, Biontech RNA, MERIT, RNA, Immuno Therapy, RB_0001-01, Ribological, Melanoma, RBL001, RBL002, cancer vaccine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RBL001/RBL002Biological
Also called cancer vaccine
Each participant will receive 8 repeated intranodal administrations of RBL001 and RBL002 during a time frame of 43 to 51 days.
| Study group | Role | What they receive |
|---|---|---|
| RBL001/RBL002 intranodal administration | Experimental | 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 Receives: Biological: RBL001/RBL002 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events
Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities
Measured: 90 days
Secondary outcomes (2)
Determination of antitumoral immune responses
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.
Measured: 90 days
Clinical Monitoring of Tumor Lesions
Tumor lesion status as determined by CT or MRI results evaluated by irRC and RECIST.
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2012 (estimated)
- Study startJun 2012
- Primary completionMay 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioNTech RNA Pharmaceuticals GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ugur Sahin, Prof. Dr., Study director, Ribological GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01684241
- Sponsor's protocol ID
- RB_0001-01
- Acronym
- MERIT
- Status last verified
- Jan 2020
- First submitted
- 10 Sep 2012
- Last updated
- 18 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01684241
- Acronym / sponsor ID
- MERIT / RB_0001-01
- Conditions
- Melanoma
- Keywords
- Biontech, Biontech RNA Pharmaceuticals GmbH, Biontech RNA, MERIT, RNA, Immuno Therapy, RB_0001-01, Ribological
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- BioNTech RNA Pharmaceuticals GmbHIndustry (pharma, biotech, devices)
- Study start
- Jun 2012
- Primary completion
- May 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 12 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| RBL001/RBL002 intranodal administration | Experimental | Biological: RBL001/RBL002All 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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)
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RBL001/RBL002Also: cancer vaccineEach participant will receive 8 repeated intranodal administrations of RBL001 and RBL002 during a time frame of 43 to 51 days. | Biological | RBL001/RBL002 intranodal administration |
Primary outcome
Number of adverse events
Time frame: 90 days
Number of Patients with adverse events, total number of adverse events, dose-limiting toxicities
2 secondary outcomes
Determination of antitumoral immune responses
Time frame: 90 days
Clinical Monitoring of Tumor Lesions
Time frame: 90 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ugur Sahin, Prof. Dr. study director
Ribological GmbH
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RBL001/RBL002 in people with Melanoma, run by BioNTech RNA Pharmaceuticals GmbH at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany, Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2020.