Hespecta Vaccination in HPV+ Tumors or Malignant Lesions

February 17, 2021 updated by: HansGelderblom, Leiden University

Phase I Study: to Determine the Biological Activity of Two HPV16 E6 Specific Peptides Coupled to Amplivant®, a Toll-like Receptor Ligand in Patients Treated for HPV16-positive Tumors or Premalignant Lesions

A phase I study to establish the highest safe dose that induces HPV16 E6-specific T-cell responses, using the highly promising novel therapeutic vaccine concept named: Hespecta (HPV E Six Peptide Conjugated To Amplivant®) to induce HPV16 E6-specific T-cell responses.

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

Human papillomavirus (HPV) has been found to be associated with several types of premalignant lesions and cancer. HPV16 is the far most common HPV type detected in these tumors and premalignant lesions. HPV16 encodes the two tumor-specific oncoproteins E6 and E7. In most humans the virus is cleared. However, in some individuals, infection results in an uncontrolled persistent HPV16 infection that due to expression of the viral oncoproteins E6 and E7 may lead to the formation of malignancies. Moreover, these oncoproteins maintain the malignant state of the transformed cells. The virus-specific interferon-γ (IFNγ)-producing cluster of differentiation 4 (CD4+) helper T cells (Th1 cells) and cluster of differentiation 8 (CD8+) cytotoxic T-lymphocytes (CTL) are able to recognize peptides processed from the highly immunogenic E6 and play a critical role in the elimination and/or control of the virus. Studies in patients with HPV associated tumors showed that the spontaneous HPV-specific T-cell responses, are weak and fail to sufficiently control tumor outgrowth. Preexisting specific T-cell responses against E6 and E7 in patients with HPV related tumors such are associated with better outcome after treatment. Since the HPV16-transformed tumor cells constitutively express the two HPV16 encoded E6 and E7 oncoproteins, these viral antigens are considered to be excellent targets for immunotherapeutic vaccine strategies aiming at reinforcing the tumor-specific T-cell response. Previous vaccination studies showed that the use of our first generation HPV16 synthetic long peptides vaccine (HPV16-SLP) was safe and highly immunogenic in patients with HPV-induced ano-genital lesions. Vaccination of patients with cervical cancer (CxCa) also resulted in the induction of HPV16-specific T-cell responses but the nature and strength of the induced T cell responses was not sufficient for the regression of these tumors. Specifically, it was concluded that the polarization of the T cell response to Th1 (IFNγ-response) was not optimal and a much stronger CD8+ T cell response was required for clinical efficacy. These results initiated the development of new HPV16 vaccination strategies that are able to polarize the induced Th1 response and obtain strong CD8+ T-cell cytotoxicity. One of these developments consists of conjugating two of the HPV16 E6 SLP to Amplivant® a synthetic Toll-like receptor (TLR) 2 ligand. These two peptides cover the most immunodominant regions of the overlapping HPV16-SLP set and contain both Th and CTL epitopes. Peptide conjugated Amplivant® has been selected because it is acknowledged for its capacity to strongly enhance antigen presentation by dendritic cells (DCs), enhance T-cell priming and cause superior induction of effective anti-tumor CTL responses in mouse tumor models, compared to a mixture of free TLR ligand and peptide. In preclinical murine studies, Amplivant®-conjugated SLP showed 10 to 100 times higher bioactivity compared to unconjugated SLP, in terms of induced immune responses. In addition, the quantity and quality of human T-cell responses, and especially the HPV16-specific CD8+ T-cell response, in cancer patients could be markedly enhanced by ex vivo stimulation with Amplivant®-conjugated SLPs.

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.
25

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 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 Locations

  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Leiden University Medical Center

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

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically documented evidence of HPV16 positive (pre)malignant lesion following standard treatment
  2. Patient with a tumor should have no evidence of residual disease based on physical examination at the completion of curative intent therapy
  3. At least four weeks and less than twelve weeks after last anti-tumor treatment
  4. Willing and able to comply with the protocol and to provide informed consent in accordance with institutional and regulatory guidelines
  5. Patients must be 18 years or older.
  6. Patients of child-bearing potential should test negative using a serum pregnancy test and agree to utilize effective contraception during the entire treatment and follow-up period of the study (up to 2 months after the last vaccination)
  7. Patients must be in good general health and ambulatory, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion Criteria:

  1. Radiotherapy, chemotherapy or other potentially immunosuppressive therapy administered within 4 weeks prior to the enrolment visit
  2. History of an autoimmune disease or other systemic intercurrent disease that might affect the immunocompetence of the patient, or patients receiving immunosuppressive therapy, except for topical application
  3. History of a second malignancy except curatively treated low-stage tumors with a histology that can be differentiated from the current tumor or premalignant lesion
  4. Receipt of another investigational product within the previous 4 weeks or at any time during the study period.
  5. Receipt of prior HPV directed immunotherapy

  6. Hematology and biochemistry:

    • Absolute Neutrophil Count (ANC) < 1.5 x 109/L, or platelet count < 100 x 109/L or hemoglobin < 6 mmol/L.
    • Serum (total) bilirubin > 2 x upper normal limit (ULN);
    • Aspartate Aminotransferase (ASAT) or Alanine Aminotransferase (ALAT) > 2.5 x ULN;
    • Alkaline phosphatase levels > 2.5 x ULN;
    • Serum creatinine > ULN or calculated clearance </= 40 mL/min/1.73 m2 for patients with serum creatinine levels above the institutional normal value
  7. Human immunodeficiency virus (HIV), chronic hepatitis B or C infection.
  8. Any condition that in the opinion of the investigator could interfere with the conduct of the 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: Other
  • Allocation: N/A
  • 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: Hespecta
Four dose groups of Hespecta
Biological: Hespecta
A dose escalation of Amplivant® conjugated peptide
Other Names:
  • HPV 16 E6 synthetic peptides (E6 71-95 and E6 127-158)

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
Biological activity of Hespecta
Time Frame: 26 weeks
Blood samples will be drawn and used in an array of complementary immunological assays to assess the biological activity of Hespecta. Vaccine induced immunity in the different assays is defined if the response after vaccination is at least 3-fold higher than the pre-vaccination response.
26 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Adverse events (AE) according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Time Frame: 26 weeks
Safety
26 weeks

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.
Leiden University

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.
Dutch Cancer Society
ISA Pharmaceuticals
Top Institute Pharma

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: H. Gelderblom, Prof.dr., Leiden University Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

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.
March 1, 2015

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.
March 1, 2020

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.
March 1, 2020

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).
June 2, 2016

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.
June 30, 2016

First Posted (Estimate)

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.
July 1, 2016

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 21, 2021

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 17, 2021

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, 2021

More Information

Terms related to this study

Keywords

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.
  • HPV16HH01

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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