Ignite Creation Date:
2024-05-06 @ 4:02 PM
Last Modification Date:
2024-10-26 @ 2:02 PM
Study NCT ID:
NCT04842682
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2022-09-14
First Post:
2021-03-24
Brief Title:
Dose Escalation Trial of CD40HIVRIEnv Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Volunteers
Sponsor:
ANRS Emerging Infectious Diseases
Organization:
ANRS Emerging Infectious Diseases
Study Overview
Official Title:
A Phase I Multicenter Double-blind Placebo Controlled Dose Escalation Trial of an Adjuvanted Anti-CD40 mAb Fused to Env GP140 HIV Clade C ZM-96 CD40HIVRIEnv Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Participants
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-08
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:
None
Brief Summary:
Multicenter double-blind placebo controlled phase I dose-escalation trial that will be conducted in France and Switzerland to evaluate different dose levels of CD40HIVRIEnv adjuvanted with Hiltonol alone and in co-administration with DNA-HIV-PT123
A total of 72 eligible healthy participants will be recruited into 6 groups Within each group participants will be randomized in a double blind manner to active intervention or placebo in a 51 ratio Enrolment into a given group other than group Solo 03 will open sequentially depending on the go-criterion based on the safety data of the preceding groups
The primary objective is to assess the safety of three dose levels of CD40HIVRIEnv 03 1 3 mg adjuvanted with Poly-ICLC Hiltonol alone and in combination with DNA-HIV-PT123 administered at weeks 0 4 and 24 in healthy participants
Secondary objectives are to assess the capacity of poly-ICLC-adjuvanted CD40HIVRIEnv alone and in combination with DNA-HIV-PT123 to elicit immune responses against HIV immunogenicity
Humoral antibody responses
B-cell responses
T-cell responses
A total of 72 eligible healthy participants will be recruited into 6 groups Within each group participants will be randomized in a double blind manner to active intervention or placebo in a 51 ratio Enrolment into a given group other than group Solo 03 will open sequentially depending on the go-criterion based on the safety data of the preceding groups
The primary objective is to assess the safety of three dose levels of CD40HIVRIEnv 03 1 3 mg adjuvanted with Poly-ICLC Hiltonol alone and in combination with DNA-HIV-PT123 administered at weeks 0 4 and 24 in healthy participants
Secondary objectives are to assess the capacity of poly-ICLC-adjuvanted CD40HIVRIEnv alone and in combination with DNA-HIV-PT123 to elicit immune responses against HIV immunogenicity
Humoral antibody responses
B-cell responses
T-cell responses
Detailed Description:
The ANRS VRI06 clinical trial follows the prophylactic vaccine strategies developed since the encouraging results obtained during the RV144 trial The RV144 study identified binding IgG antibodies directed at conserved regions of the V1V2 loop and antibody-dependent cell-mediated cytotoxicity as immune correlates of reduced risk of HIV infection in the absence of inhibiting serum IgA antibodies
We have developed DC-targeting vaccines in order to increase protein antigen efficacy through their selective delivery to dendritic cell DC the key cell type for initiating and regulating immune responses via the endocytic receptors expressed at the DC surfaces Following the screening of vaccines targeting different several DC-receptors the CD40-targeting vaccine has been shown to be the best candidate for inducing both cellular and humoral responses Anti-CD40Env GP140 vaccine CD40HIVRIEnv adjuvanted with Poly-ICLC Hiltonol in a primeboost association with poxvirus vector vaccines has shown to be safe and elicit robust Env specific T and B cell responses in a non-human primate study
In this trial we will also capitalize on data generated in a recent phase III trial showing that co-administration of DNA-HIV-PT123 with an Env protein vaccine as compared to other vaccine regimens which do not co-administer the protein during the priming results in the rapid generation of high titers of binding anti V1V2 Env region IgG Abs and Tier 1 nAb responses HVTN 096 study
We therefore hypothesize that co-administration of CD40HIVRIEnv adjuvanted with Poly-ICLC Hiltonol with the DNA-HIV-PT123 vaccine will be safe and induce high titers of binding anti V1V2 Env region IgG Abs and other immunological parameters considered as immune correlates in RV144 trial
When the first 6 participants of given dose group have reached W6 2 weeks after the second injection the Protocol Safety Review Team PSRT composed of sponsors pharmacovigilance expert coordinating investigator co-coordinating investigator and methodologist will review all accumulated Adverse Event AE data so far in a blinded manner All AE in particular grade 3 and grade 4 AEs as well as Serious Adverse Events SAEs will be reviewed The current version FDA grading scale will be used for grading
Go-criterion for opening enrolment into the next groups If no grade 3 or 4 clinical solicited localsystemic or unsolicited AE or grade 3 or 4 biological clinical significant is reported at W6 in any of the first 6 participants of a given group the Data and Safety Monitoring Board DSMB assessment will not be requested for the go to the next group and the go-criterion is met The trial can be continued by opening to the inclusions following the protocol
Otherwise occurrence of grade 3 or 4 AE the DSMB will review all accumulated AE data Enrolment in next group will only start after the DSMB gives the green light
In addition the following pausing rule pausing of all injections will apply during the trial
Pausing rule for vaccine related safety events If a serious adverse reaction relatedness as judged by the pharmacovigilance department or the investigator responsible of the SAE notification is reported during any stage of the study all vaccinations will be halted inclusions in the trial will be suspended competent authorities must be informed and an ad-hoc DSMB meeting convened for recommendations on the trial continuation Vaccinations may resume only after authorization is given by competent authority
By the conservative method if the causality assessment could not be provided by the investigator the AE will be considered as possibly related
We have developed DC-targeting vaccines in order to increase protein antigen efficacy through their selective delivery to dendritic cell DC the key cell type for initiating and regulating immune responses via the endocytic receptors expressed at the DC surfaces Following the screening of vaccines targeting different several DC-receptors the CD40-targeting vaccine has been shown to be the best candidate for inducing both cellular and humoral responses Anti-CD40Env GP140 vaccine CD40HIVRIEnv adjuvanted with Poly-ICLC Hiltonol in a primeboost association with poxvirus vector vaccines has shown to be safe and elicit robust Env specific T and B cell responses in a non-human primate study
In this trial we will also capitalize on data generated in a recent phase III trial showing that co-administration of DNA-HIV-PT123 with an Env protein vaccine as compared to other vaccine regimens which do not co-administer the protein during the priming results in the rapid generation of high titers of binding anti V1V2 Env region IgG Abs and Tier 1 nAb responses HVTN 096 study
We therefore hypothesize that co-administration of CD40HIVRIEnv adjuvanted with Poly-ICLC Hiltonol with the DNA-HIV-PT123 vaccine will be safe and induce high titers of binding anti V1V2 Env region IgG Abs and other immunological parameters considered as immune correlates in RV144 trial
When the first 6 participants of given dose group have reached W6 2 weeks after the second injection the Protocol Safety Review Team PSRT composed of sponsors pharmacovigilance expert coordinating investigator co-coordinating investigator and methodologist will review all accumulated Adverse Event AE data so far in a blinded manner All AE in particular grade 3 and grade 4 AEs as well as Serious Adverse Events SAEs will be reviewed The current version FDA grading scale will be used for grading
Go-criterion for opening enrolment into the next groups If no grade 3 or 4 clinical solicited localsystemic or unsolicited AE or grade 3 or 4 biological clinical significant is reported at W6 in any of the first 6 participants of a given group the Data and Safety Monitoring Board DSMB assessment will not be requested for the go to the next group and the go-criterion is met The trial can be continued by opening to the inclusions following the protocol
Otherwise occurrence of grade 3 or 4 AE the DSMB will review all accumulated AE data Enrolment in next group will only start after the DSMB gives the green light
In addition the following pausing rule pausing of all injections will apply during the trial
Pausing rule for vaccine related safety events If a serious adverse reaction relatedness as judged by the pharmacovigilance department or the investigator responsible of the SAE notification is reported during any stage of the study all vaccinations will be halted inclusions in the trial will be suspended competent authorities must be informed and an ad-hoc DSMB meeting convened for recommendations on the trial continuation Vaccinations may resume only after authorization is given by competent authority
By the conservative method if the causality assessment could not be provided by the investigator the AE will be considered as possibly related
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 |
|---|---|---|---|
| ANRS VRI06 | OTHER | ANRS | None |