HPVEarly Phase 1PANHPVAXNCT05208710
PANHPVAX, Study of a New HPV Vaccine in Healthy Volunteers
A Early Phase 1 study testing Vaccination with PANHPVAX 10µg, Vaccination with PANHPVAX 40µg and Vaccination with PANHPVAX 100µg in people with HPV, run by German Cancer Research Center at 1 site in Germany.
Trial summary
First-in-human, phase I, single-center, open-label, dose-escalation trial in healthy volunteers. Investigation of safety and tolerability of ascending doses of PANHPVAX, a vaccine against human papilloma L2 antigens formulated with cdA (adjuvant) as compared to the formulation without cdA. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- HPV
- What is being tested?
- Vaccination with PANHPVAX 10µg, Vaccination with PANHPVAX 40µg and Vaccination with PANHPVAX 100µg
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteGermany
- Study dates
- 7 Nov 2022to Dec 2027
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
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 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Written, personally signed and dated informed consent to participate in the trial prior to any trial-related interventions,
- Understanding, ability, and willingness to fully comply with trial interventions and restrictions,
- Age 18-45 years (y) inclusive at the time of consent,
- Males or females of child-bearing potential who are willing to use a highly effective method of contraception during the treatment and for 4 weeks after each vaccination with the IMP, or women not of child-bearing potential (WNCBP), or individuals who are convincingly sexually abstinent. Highly effective methods of contraception are described in section 7.6.9,
- No current desire to have children, and
- Consent not to be vaccinated with a commercially available HPV vaccine during the trial until the end-of-study visit.
Who cannot join
- Clinically significant or relevant abnormalities as assessed by the investigator in the medical history, or findings from physical examination, or laboratory evaluation that may require treatment or make the participant unlikely to fully complete the trial, or any condition that presents undue risk from the IMP or trial interventions,
- Any acute or chronic illness expected to influence the immune response to vaccination,
- Immunoglobulin administration in the past 3 months prior to first immunization,
- Any known history of severe anaphylactic reactions to drugs or vaccinations, or any known history to allergies against the excipients of the investigational medicinal product (IMP),
- Clinically relevant findings in any of the following investigations at screening (SCR) I. Hemoglobin (Hb) < 12 g/dl (males) or < 11 g/dl (females), II. Estimated Creatinine clearance (eCrCl) < 60 ml/min (Cockcroft-Gault), III. Total bilirubin > upper limit of normal (ULN) x 1.2; In case of suspected Gilbert´s disease: total bilirubin ≤ ULN x 3 is acceptable , IV. Alanine aminotransferase (ALT) > ULN x 1.1, V. Aspartate aminotransferase (AST) > ULN x 1.2,
- Use of an IMP within 30 d prior to the expected date of receiving the first dose of IMP or active enrolment in another drug or vaccine clinical trial,
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- Use of any medication (prescription medication, non-prescription medication including herbal preparations) with active ingredients (except hormonal contraception, iodine, and thyroid hormones) within a period of less than 5 times the respective elimination half-life (t1/2) with regard to the expected date of the first dose of IMP. This does not apply to topical preparations if no relevant systemic exposure is expected,
- Known prior vaccination against HPV,
- Any vaccination within the 28 days (d) prior to the expected Visit 1,
- A positive human immunodeficiency virus (HIV) or hepatitis C (HCV) antibody screen, or positive result for Hepatitis-B-Surface-Antigen (HBsAg),
- A positive result in the drug screening test at SCR, and
- Pregnancy or breast feeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site, 1 recruiting
- Recruiting
University Hospital Department of Clinical Pharmacology and Pharmacoepidemiology
Heidelberg, 69120
Antje Blank, PD Dr. med, antje.blank@med.uni-heidelberg.de
Katja Gümüs, Dr. med, KatjaSusanne.Guemues@med.uni-heidelberg.de
About this study
Official title: A First-in-human, Phase I, Single-center, Open-label, Dose-escalation Trial in Healthy Volunteers to Assess Safety, Tolerability, and Immunogenicity of PANHPVAX, a Vaccine Targeting Human Papilloma L2 Antigen Formulated With Cyclic Di-AMP
First-in-human, phase I, single-center, open-label, dose-escalation trial in healthy volunteers. Investigation of safety and tolerability of ascending doses of PANHPVAX, a vaccine against human papilloma L2 antigens formulated with cdA (adjuvant) as compared to the formulation without cdA.
Read the detailed description
Infections with one of 15 human papillomavirus (HPV) types are considered the main risk factor for the development of certain anogenital cancers. In addition, these HPV types are also suspected to be causatively involved in oropharyngeal cancer. Three commercial vaccines are currently available, which are inducing prophylactic neutralizing antibody responses against the L1 major capsid protein. The vaccines are cocktails of L1 virus-like particles of two to nine different HPV types. L1 is not preserved between serotypes, therefore, the specific immune responses, are limited to the HPV types represented by the vaccine. In contrast, the L2 minor capsid protein harbors a so called major cross-neutralization epitope in its amino terminus, which has a high homology between serotypes. The PANHPVAX vaccine is based on this epitope.
Specifically, a polytope containing the epitope of eight HPV types is inserted into a scaffold of thioredoxin from the archaeon Pyrococcus furiosus. Further, the antigen is multimerized by a heptamerization domain. To increase immunogenicity, the protein is formulated with the di-nucleotide adjuvant cyclic di-adenosine monophosphate (used abbreviations: cyclic di-AMP / c-di-AMP/ cdA), an inducer of cellular STING (Stimulator of Interferon Genes). In preclinical models, PANHPVAX induces neutralizing antibodies against all cancer-causing HPV types as well as the major types causing benign genital warts. Also, neutralizing antibodies are induced against a number of cutaneous HPV that are suspected to play a role in skin carcinogenesis and/or cause morbidity in immunocompromised patients.
The investigators aim to translate the vaccine into clinical use and conduct a first-in-human single-center dose-escalation trial in healthy volunteers with an intramuscular (i.m.) prime and two i.m. booster injections to demonstrate safety, tolerability, and immunogenicity of the PANHPVAX antigen. The vaccine will be administered in escalating doses and with increasing amount of the adjuvant cdA (novel excipient) in the formulation, in each dose cohort starting with a group of volunteers who will receive the vaccine without adjuvant. Individual participants will be treated three times with identical doses at months 1, 3, and 6 and followed up for safety and tolerability. Induction of neutralizing antibody responses will be determined by pseudovirion-based neutralization assay (PBNA), the current gold standard for monitoring HPV prophylactic vaccines.
Volunteers will be vaccinated with PANHPVAX antigen, reconstituted for administration with novel excipient cdA as adjuvant and dilution buffer. Each volunteer is scheduled to receive three identical vaccine doses. The initial (prime) vaccination is followed by two booster vaccinations one and six months thereafter (Figure 1). After each administration, a close follow-up for vaccination reactions will occur for 29 ± 3 d and a long-term safety follow-up will be scheduled about 13 months after the first vaccine dose (= 6 months after the last vaccine dose).
Dose-escalation cohorts are defined by the antigen dose. Within each cohort, three dose groups of volunteers will receive the vaccine with escalating doses of adjuvant (no adjuvant/0 µg, 7.5 µg, and 15 µg cdA) in the formulation, always starting with a group of 3 volunteers who will receive PANHPVAX formulated without adjuvant. This is followed by two consecutive groups of 6 volunteers each receiving the same antigen dose in combination with ascending doses of adjuvant.
After the first administration of each dose combination of antigen and adjuvant ("prime"), safety observation periods will be longer and the first two participants in each dose group will be exposed separately. Thereafter, all further volunteers of a group may be dosed in parallel. In the two subsequent boosting phases, 2 participants per dose group are planned to be exposed first and observation periods between subsequent enrolment will be slightly shorter. New dose cohorts may be opened as soon as the data safety monitoring board (DSMB) assessed the safety data available after the 15th participant of a cohort has received his/her second vaccine administration (= 1st boost) and has been observed for 7 d.The DSMB will evaluate the data and provide its recommendation on continuation.
- Conditions
- HPV
- Being tested
- Vaccination with PANHPVAX 10µg, Vaccination with PANHPVAX 40µg, Vaccination with PANHPVAX 100µg
- Keywords
- HPV Vaccines, Cyclic-di AMP, First in Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaccination with PANHPVAX 10µgBiological
Escalated dosages of c-di AMP (0, 7,5, 15µg) added groupwise to 10µg antigen
Vaccination with PANHPVAX 40µgBiological
Escalated dosages of c-di AMP (0, 7,5, 15µg) added groupwise to 40µg antigen
Vaccination with PANHPVAX 100µgBiological
Escalated dosages of c-di AMP (0, 7,5, 15µg) added groupwise to 100µg antigen
| Study group | Role | What they receive |
|---|---|---|
| PANHPVAX 10µg | Experimental | PANHPVAX 10µg plus c-di AMP in escalating doses Receives: Biological: Vaccination with PANHPVAX 10µg |
| PANHPVAX 40µg | Experimental | PANHPVAX 40µg plus c-di AMP in escalating doses Receives: Biological: Vaccination with PANHPVAX 40µg |
| PANHPVAX 100µg | Experimental | PANHPVAX 100µg plus c-di AMP in escalating doses Receives: Biological: Vaccination with PANHPVAX 100µg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency and severity of local and systemic reactions
Frequency and severity of local and systemic reactions (solicited vaccination reactions) of ascending doses of the vaccine after each vaccination until day 29.
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start7 Nov 2022
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HPVStudies 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
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- German Cancer Research Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Heidelberg, National Center for Tumor Diseases, Heidelberg
- Responsible party
- Sponsor
- Investigators
- Antje Blank, Dr., Principal investigator, Heidelberg University Hospital, Department of Clinical Pharmacology and Pharmacoepidemiology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05208710
- Sponsor's protocol ID
- DKFZ-2019-003
- Other IDs
- 2021-002584-22
- Acronym
- PANHPVAX
- Status last verified
- Oct 2025
- First submitted
- 12 Jan 2022
- Last updated
- 19 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-in-human, Phase I, Single-center, Open-label, Dose-escalation Trial in Healthy Volunteers to Assess Safety, Tolerability, and Immunogenicity of PANHPVAX, a Vaccine Targeting Human Papilloma L2 Antigen Formulated With Cyclic Di-AMP
- ClinicalTrials.gov ID
- NCT05208710
- Acronym / sponsor ID
- PANHPVAX / DKFZ-2019-003
- Conditions
- HPV
- Keywords
- HPV Vaccines, Cyclic-di AMP, First in Human
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- German Cancer Research CenterUniversity, hospital or other
- Collaborators
- University Hospital Heidelberg, National Center for Tumor Diseases, Heidelberg
- Study start
- 7 Nov 2022 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 26 Jan 2022 (actual)
- 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.
First-in-human, phase I, single-center, open-label, dose-escalation trial in healthy volunteers. Investigation of safety and tolerability of ascending doses of PANHPVAX, a vaccine against human papilloma L2 antigens formulated with cdA (adjuvant) as compared to the formulation without cdA.
Detailed description
Infections with one of 15 human papillomavirus (HPV) types are considered the main risk factor for the development of certain anogenital cancers. In addition, these HPV types are also suspected to be causatively involved in oropharyngeal cancer. Three commercial vaccines are currently available, which are inducing prophylactic neutralizing antibody responses against the L1 major capsid protein. The vaccines are cocktails of L1 virus-like particles of two to nine different HPV types. L1 is not preserved between serotypes, therefore, the specific immune responses, are limited to the HPV types represented by the vaccine. In contrast, the L2 minor capsid protein harbors a so called major cross-neutralization epitope in its amino terminus, which has a high homology between serotypes. The PANHPVAX vaccine is based on this epitope.
Specifically, a polytope containing the epitope of eight HPV types is inserted into a scaffold of thioredoxin from the archaeon Pyrococcus furiosus. Further, the antigen is multimerized by a heptamerization domain. To increase immunogenicity, the protein is formulated with the di-nucleotide adjuvant cyclic di-adenosine monophosphate (used abbreviations: cyclic di-AMP / c-di-AMP/ cdA), an inducer of cellular STING (Stimulator of Interferon Genes). In preclinical models, PANHPVAX induces neutralizing antibodies against all cancer-causing HPV types as well as the major types causing benign genital warts. Also, neutralizing antibodies are induced against a number of cutaneous HPV that are suspected to play a role in skin carcinogenesis and/or cause morbidity in immunocompromised patients.
The investigators aim to translate the vaccine into clinical use and conduct a first-in-human single-center dose-escalation trial in healthy volunteers with an intramuscular (i.m.) prime and two i.m. booster injections to demonstrate safety, tolerability, and immunogenicity of the PANHPVAX antigen. The vaccine will be administered in escalating doses and with increasing amount of the adjuvant cdA (novel excipient) in the formulation, in each dose cohort starting with a group of volunteers who will receive the vaccine without adjuvant. Individual participants will be treated three times with identical doses at months 1, 3, and 6 and followed up for safety and tolerability. Induction of neutralizing antibody responses will be determined by pseudovirion-based neutralization assay (PBNA), the current gold standard for monitoring HPV prophylactic vaccines.
Volunteers will be vaccinated with PANHPVAX antigen, reconstituted for administration with novel excipient cdA as adjuvant and dilution buffer. Each volunteer is scheduled to receive three identical vaccine doses. The initial (prime) vaccination is followed by two booster vaccinations one and six months thereafter (Figure 1). After each administration, a close follow-up for vaccination reactions will occur for 29 ± 3 d and a long-term safety follow-up will be scheduled about 13 months after the first vaccine dose (= 6 months after the last vaccine dose).
Dose-escalation cohorts are defined by the antigen dose. Within each cohort, three dose groups of volunteers will receive the vaccine with escalating doses of adjuvant (no adjuvant/0 µg, 7.5 µg, and 15 µg cdA) in the formulation, always starting with a group of 3 volunteers who will receive PANHPVAX formulated without adjuvant. This is followed by two consecutive groups of 6 volunteers each receiving the same antigen dose in combination with ascending doses of adjuvant.
After the first administration of each dose combination of antigen and adjuvant ("prime"), safety observation periods will be longer and the first two participants in each dose group will be exposed separately. Thereafter, all further volunteers of a group may be dosed in parallel. In the two subsequent boosting phases, 2 participants per dose group are planned to be exposed first and observation periods between subsequent enrolment will be slightly shorter. New dose cohorts may be opened as soon as the data safety monitoring board (DSMB) assessed the safety data available after the 15th participant of a cohort has received his/her second vaccine administration (= 1st boost) and has been observed for 7 d.The DSMB will evaluate the data and provide its recommendation on continuation.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PANHPVAX 10µg | Experimental | Biological: Vaccination with PANHPVAX 10µgPANHPVAX 10µg plus c-di AMP in escalating doses |
| PANHPVAX 40µg | Experimental | Biological: Vaccination with PANHPVAX 40µgPANHPVAX 40µg plus c-di AMP in escalating doses |
| PANHPVAX 100µg | Experimental | Biological: Vaccination with PANHPVAX 100µgPANHPVAX 100µg plus c-di AMP in escalating doses |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Written, personally signed and dated informed consent to participate in the trial prior to any trial-related interventions,
- Understanding, ability, and willingness to fully comply with trial interventions and restrictions,
- Age 18-45 years (y) inclusive at the time of consent,
- Males or females of child-bearing potential who are willing to use a highly effective method of contraception during the treatment and for 4 weeks after each vaccination with the IMP, or women not of child-bearing potential (WNCBP), or individuals who are convincingly sexually abstinent. Highly effective methods of contraception are described in section 7.6.9,
- No current desire to have children, and
Key exclusion criteria (12 listed)
- Clinically significant or relevant abnormalities as assessed by the investigator in the medical history, or findings from physical examination, or laboratory evaluation that may require treatment or make the participant unlikely to fully complete the trial, or any condition that presents undue risk from the IMP or trial interventions,
- Any acute or chronic illness expected to influence the immune response to vaccination,
- Immunoglobulin administration in the past 3 months prior to first immunization,
- Any known history of severe anaphylactic reactions to drugs or vaccinations, or any known history to allergies against the excipients of the investigational medicinal product (IMP),
- Clinically relevant findings in any of the following investigations at screening (SCR) I. Hemoglobin (Hb) < 12 g/dl (males) or < 11 g/dl (females), II. Estimated Creatinine clearance (eCrCl) < 60 ml/min (Cockcroft-Gault), III. Total bilirubin > upper limit of normal (ULN) x 1.2; In case of suspected Gilbert´s disease: total bilirubin ≤ ULN x 3 is acceptable , IV. Alanine aminotransferase (ALT) > ULN x 1.1, V. Aspartate aminotransferase (AST) > ULN x 1.2,
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 |
|---|---|---|
| Vaccination with PANHPVAX 10µgEscalated dosages of c-di AMP (0, 7,5, 15µg) added groupwise to 10µg antigen | Biological | PANHPVAX 10µg |
| Vaccination with PANHPVAX 40µgEscalated dosages of c-di AMP (0, 7,5, 15µg) added groupwise to 40µg antigen | Biological | PANHPVAX 40µg |
| Vaccination with PANHPVAX 100µgEscalated dosages of c-di AMP (0, 7,5, 15µg) added groupwise to 100µg antigen | Biological | PANHPVAX 100µg |
Primary outcome
Frequency and severity of local and systemic reactions
Time frame: 3 months
Frequency and severity of local and systemic reactions (solicited vaccination reactions) of ascending doses of the vaccine after each vaccination until day 29.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2025.
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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.
Antje Blank, Dr. principal investigator
Heidelberg University Hospital, Department of Clinical Pharmacology and Pharmacoepidemiology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vaccination with PANHPVAX 10µg, Vaccination with PANHPVAX 40µg and Vaccination with PANHPVAX 100µg in people with HPV, run by German Cancer Research Center at 1 site in Germany.
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 6 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 19 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Markus Kratzmann, Dr. (+49 (0)6221 56 32014, markus.kratzmann@nct-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency and severity of local and systemic reactions (time frame: 3 months). 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 19 Dec 2025.