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HPV Anti-CD40 RNA Vaccine (HARE-40)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03418480
Recruitment Status : Suspended (Temporary suspension due to COVID-19 pandemic)
First Posted : February 1, 2018
Last Update Posted : March 26, 2020
BioNTech SE
Information provided by (Responsible Party):
University of Southampton

Tracking Information
First Submitted Date  ICMJE November 15, 2017
First Posted Date  ICMJE February 1, 2018
Last Update Posted Date March 26, 2020
Actual Study Start Date  ICMJE April 11, 2017
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 31, 2018)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE HPV Anti-CD40 RNA Vaccine
Official Title  ICMJE Therapeutic HPV Vaccine Trial +/- Anti-CD40 in HPV-driven Squamous Cell Carcinoma
Brief Summary

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 or cervical) using a single cohort to establish a safe, tolerable and recommended dose of HPV vaccine.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma, Squamous Cell
  • Head and Neck Neoplasm
  • Cervical Neoplasm
  • Penile Neoplasms Malignant
Intervention  ICMJE Drug: HPV vaccine
Intradermal vaccine
Study Arms  ICMJE
  • 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.
    Intervention: Drug: HPV vaccine
  • Experimental: RAN Vaccine B
    Arm 1B: 29 (15+14) patients with HPV16+ advanced disease receiving increasing doses of HPV vaccine.
    Intervention: Drug: HPV vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: January 31, 2018)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date March 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
  • Patient with a history of anaphylactic reactions or severe allergies are excluded.
  • 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
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 United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03418480
Other Study ID Numbers  ICMJE RHMCAN0983
2014-002061-30 ( EudraCT Number )
ISRCTN51789191 ( Other Identifier: ISRCTN Reference No. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Southampton
Study Sponsor  ICMJE University of Southampton
Collaborators  ICMJE BioNTech SE
Investigators  ICMJE
Principal Investigator: Christian Ottensmeier, Prof University Hospitals Southampton NHS Foundation Trust
PRS Account University of Southampton
Verification Date March 2020

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