Ignite Creation Date:
2024-05-06 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 2:23 PM
Study NCT ID:
NCT05208710
Status:
RECRUITING
Last Update Posted:
2023-08-02
First Post:
2022-01-12
Brief Title:
PANHPVAX Study of a New HPV Vaccine in Healthy Volunteers
Sponsor:
German Cancer Research Center
Organization:
German Cancer Research Center
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PANHPVAX
Brief 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
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 andor 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 im prime and two im 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 adjuvant0 µg 75 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 hisher second vaccine administration 1st boost and has been observed for 7 dThe DSMB will evaluate the data and provide its recommendation on continuation
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 andor 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 im prime and two im 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 adjuvant0 µg 75 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 hisher second vaccine administration 1st boost and has been observed for 7 dThe DSMB will evaluate the data and provide its recommendation on continuation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2021-002584-22 | EUDRACT_NUMBER | None | None |