HARE-40: HPV Anti-CD40 RNA vaccinE (HARE-40)

February 6, 2024 updated by: University of Southampton

Therapeutic HPV Vaccine (BNT113) Trial in HPV16 Driven Carcinoma

HARE-40 is a phase I/II vaccine dose escalation study with two different arms: Arm 1A will perform intrapatient dose escalation in patients with previously treated HPV16+ Head & Neck Cancer using two dose cohorts to establish a safe, tolerable and recommended dose of HPV vaccine.

Arm 1B will perform intrapatient dose escalation in patients with advanced HPV16+ cancer (head and neck, anogenital, penile, cervical and other) using a single cohort to establish a safe, tolerable and recommended dose of HPV vaccine.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

HARE-40 is a phase I/II vaccine dose escalation trial with two arms (Arm 1A and Arm 1B) in which we will test BNT113 as monotherapy. We will undertake a multi-centre phase I, open label trial in patients with previous HPV16+ HNSCC without current clinical evidence of disease (Arm 1A) and in patients with HPV16+ advanced disease (Arm 1B). The HPV16 antigen-specific immune response will be evaluated before and after treatment in circulating blood and, where samples have been collected, in tumour and skin biopsies.

Arms 1A and 1B will escalate BNT113 in each patient (intrapatient dose escalation) up to the specified target dose of the cohort to establish a safe, tolerable and recommended dose of BNT113 in patents who are disease free (Arm 1A) and those with advanced disease (Arm 1B).

Subset of patients in Arm 1B will also be assessed for response to the vaccine in terms of a significant increase of immune cells following BNT113 administration and according to irRECIST1.1 (all 29 patients including the expansion cohort) and other endpoints.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United Kingdom
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • Univeristy Hospitals Southampton NHS Foundation Trust

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

Arm 1A:

  • Previous HPV16+ head and neck squamous cell carcinoma.
  • At least 12 months after completion of treatment.
  • Within 5 years of treatment completion.
  • Currently no clinical evidence of disease.
  • ECOG performance status 0 or 1.

Arm 1B:

  • HPV16+ head and neck, cervical, anogenital and penile carcinoma patients with recurrent disease.
  • Intention to treat is palliative.
  • Patient willing to have repeated tumour biopsies and re-biopsy deemed safe and feasible clinically.
  • Tissue samples available confirming HPV16+ disease to send to Central Laboratory.

Exclusion Criteria:

  • Patients unable to consent.
  • Any patient who has been previously vaccinated in any Arm of the trial.
  • <18 years
  • Systemic steroids (prednisolone >10 mg/day or equivalent) or other drugs with a likely effect on immune competence are forbidden during the trial. The predictable need of their use will preclude the patient from trial entry. Replacement steroids for adrenal insufficiency/failure are allowed.
  • Major surgery in the preceding three to four weeks, which the patient has not yet recovered from.
  • Patients who are of high medical risk because of non-malignant systemic disease, as well as those with active uncontrolled infection.
  • Patients with clinically relevant autoimmune disease will be excluded.
  • Patients who are known to be allergic to any of the excipients or constituents of the vaccine
  • Patients with any other condition which in the Investigator's opinion would not make the patient a good candidate for the clinical trial, such as concurrent congestive heart failure or prior history of New York Heart Association (NYHA) class III/IV cardiac disease.
  • Current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study.
  • Patients who are serologically positive for or are known to suffer from Hepatitis B, C, Syphilis or HIV. Counselling will be offered to all patients prior to testing.
  • Patients who have a positive pregnancy test or who are breast feeding.
  • Fertile males or females who are unable or unwilling to use an effective method of birth control (eg. condom with spermicide, diaphragm with spermicide, birth control pills, injections, patches, intrauterine device, or intrauterine hormone-releasing system) during study treatment and until 28 days after patients finish the study treatment.
  • Elevated Liver Function Tests - ALT >3.0 x ULN, AST >3.0 x ULN, Bilirubin >3.0 x ULN.
  • Any other investigational drug within 28 days or 5 half-lives depending on what gives the longer range before the first treatment of this study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RNA Vaccine A

Arm 1A: 15 (6+9) patients with previously treated HPV16+ head and neck squamous cell carcinoma receiving increasing doses of HPV vaccine.

- COMPLETE no longer recruiting
Drug: BNT113
Intradermal vaccine
Experimental: RAN Vaccine B

Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine.

OPEN to recruitment
Drug: BNT113
Intradermal vaccine

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Dose Limiting Toxicity (DLT) according to CTCAE version 4.03 (Arm 1A)
Time Frame: 3 months
Safe and tolerable dose of clinically disease free patients (Arm 1A) - Determination of a suitable dose of HPV RNA
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Southampton

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
BioNTech SE

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ioannis Karydis, Dr, University Hospitals Southampton NHS Foundation Trust
  • Study Chair: Christian Ottensmeier, Prof, University of Liverpool

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 11, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 24, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 15, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 31, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 1, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 7, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 6, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RHMCAN0983
  • 2014-002061-30 (EudraCT Number)
  • ISRCTN51789191 (Other Identifier: ISRCTN Reference No.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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