Evaluating a Combination of Immune-based Therapies to Achieve a Remission of HIV Infection (HIVACAR)
Primary Purpose
HIV Infections
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
HIVACAR
placebo
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring HIV
Eligibility Criteria
Inclusion Criteria:
- Between ≥ 18 to <60 years of age
- Voluntarily signed informed consent
- Male, or female with negative pregnancy test prior to enrolment
- Proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART)
- Must be on stable treatment with cART for at least 18 months (cART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents; periods of mono/dual antiretroviral therapy if not first time therapy and confirmed viral suppression during these periods of mono/dual therapy are permitted)
- Nadir CD4+ cell counts must be above or equal to 350 cells/µl, 2-3 occasional determinations below 350 cells/μl are allowed.
- Current CD4+ cell count must be at least 450 cells/µl
- HIV-RNA must be below 50 copies/ mL for the last 12 months prior to inclusion, during at least two measurements (occasional so called 'blips' up to 500 copies/mL are permitted)
If male or female of childbearing potential willing to take correct contraceptive measures:
- If heterosexually active female; using an effective method of contraception from 14 days prior to the first vaccination until at least 12 weeks after the last vaccination; all female volunteers must be willing to undergo urine or serum pregnancy tests at time points specified in the Schedule of Procedures.
- If heterosexually active male; willing to use an effective method of contraception or agree on the use of an effective method of contraception by his partner from the day of the first vaccination until 12 weeks after the last vaccination.
- If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (which could include pre-exposure prophylaxis [PrEP] for their sexual partners)
Exclusion Criteria:
- Treatment with a non-cART regimen of antiretroviral agents prior to the start of any antiretroviral regimen
- History of a CDC class C event (see Appendix IV)
- Women of childbearing potential with a positive pregnancy test, or participants (male or female) who wish to plan a pregnancy during the trial period.
- Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit
- Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit
- Use of anti-coagulant medication
- Use of any investigational drug during the 90 days prior to study entry
- Previous antiretroviral therapy failure and/or mutations conferring genotypic resistance to antiretroviral therapy
- Participants with severe cardiovascular diseases or long QT interval
- Active hepatitis C virus
- Hepatitis B infection
- Treatment with strong inhibitors or inducers of CYP3A4, except protease inhibitors for HIV treatment (see protocol section 5.7); if in treatment of protease inhibitors for HIV not willing to change inhibitor protease for an integrase inhibitor during the study.
- Any known allergy or intolerance to any of the study drugs or excipient
- Protein egg allergy
- Known past history of clinical Epstein-Barr Virus (EBV) infection or recurrent herpes zoster
- Hematologic abnormalities ≥Grade 1
- Potassium or magnesium levels outside the upper limit of normal (ULN) and lower limit of normal (LLN)
- History of autoimmune disorders as multiple sclerosis.
- Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
HIVACAR
Placebo
Arm Description
Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 dose of 10-1074 antibodies and 3 doses of romidepsin
Participants will receive 5 doses of placebo, 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Outcomes
Primary Outcome Measures
Grade 3 or above severe local , systemic, clinical or laboratory adverse event t
Local adverse events may be pain, cutaneous reactions including induration and systemic emperature, chills, headache, nausea, vomiting, malaise, and myalgia. Clinical and laboratory must be confirmed at examination or on repeat testing respectively. Any adverse event attributable to the combination therapy leading to discontinuation of the study treatmen
Secondary Outcome Measures
Proportion of participants who maintain an undetectable viral load
defined as a viral load below the threshold of 50 copies/ml
Percentage of participants with control of viral load below detectable level
Change from baseline in total proviral HIV-1 DNA per 10^6 CD4+ T cells.
Change from baseline in integrated proviral HIV-1 DNA per 10^6 CD4+ T cells.
Change from baseline in HIV-1 transcription.
According to CA US HIV-1 RNA measured in unfractionated CD4+ T cells
Change in plasma HIV-1 RNA from baseline
Breadth and magnitude of CD4+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline.
Breadth and magnitude of CD8+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline.
Breadth and magnitude of CD4+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline.
Breadth and magnitude of CD8+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline.
Change from baseline in CD8+ T-cell HIV suppressive capacity.
Change from baseline in T cell activation markers
Change from baseline in T cell activation markers
Change from baseline in T cell activation markers
Change from baseline in T cell subset distribution
Change from baseline in T cell subset distribution
Change from baseline in T cell subset distribution
Change from baseline in PD-1 expression
Evaluate fecal microbiome
Characterise viral escape from vaccine-induced immune T cell responses
Comparison of viral sequences pre-cART and rebounding after cART interruption
Analysis of changes in sensitivity to neutralisation by 10-1074 of rebounding viruses after cART interruption to identify neutralisation escape mutants.
To evaluate mRNA expression profiles in whole PBMC at baseline
Full Information
NCT ID
NCT03619278
First Posted
March 14, 2018
Last Updated
March 27, 2020
Sponsor
David Garcia Cinca
Collaborators
IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer, Felipe García - Investigator Coordinator
1. Study Identification
Unique Protocol Identification Number
NCT03619278
Brief Title
Evaluating a Combination of Immune-based Therapies to Achieve a Remission of HIV Infection
Acronym
HIVACAR
Official Title
A Phase I/IIa, Randomised Study to Evaluate the Safety and the Effectiveness of a Combination of Therapeutic Vaccine, Broadly Neutralising Antibody (10-1074), and the Latency Reversing Agent Romidepsin to Achieve a Remission of HIV Infection in Chronically HIV-infected Participants Under Stable Combined Antiretroviral Therapy.
Study Type
Interventional
2. Study Status
Record Verification Date
March 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2020 (Anticipated)
Primary Completion Date
July 15, 2021 (Anticipated)
Study Completion Date
July 15, 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
David Garcia Cinca
Collaborators
IDIBAPS - Institut d'Investigacions Biomèdiques August Pi i Sunyer, Felipe García - Investigator Coordinator
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A phase I/IIa, multinational, multicentric (IDIBAPS, IRSICAIXA, AARHUS, VUB, APHP), randomised, balanced by centre (to include participants from the 4 arms), open-label, controlled clinical trial. Each participant will be followed up a different time according to study arm: a minimum of 38 weeks in arm I, 31 weeks in arm II, 54 weeks in arm III and 26 weeks in the arm 4. The study duration will be 104 weeks from inclusion of the first participant.
Participants will be randomised to one of the following 4 arms:
Arm 1 (study): 14 participants will receive 3 vaccines of HIVARNA01.3 prime, 2 MVA-vectored vaccine boosts, 1 dose of 10-1074 antibodies and 3 doses of romidepsin
Arm 2 (study): 14 participants will receive 5 vaccines of HIVARNA01.3, 1 dose of 10-1074 antibodies and 3 doses of romidepsin
Arm 3 (study): 14 participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 1 dose of 10-1074 antibodies and 3 doses of romidepsin
Arm 4 (control): 14 participants 1 dose of 10-1074 antibodies and 3 doses of romidepsin
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
HIV
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Placebo
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HIVACAR
Arm Type
Experimental
Arm Description
Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 dose of 10-1074 antibodies and 3 doses of romidepsin
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive 5 doses of placebo, 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Intervention Type
Other
Intervention Name(s)
HIVACAR
Intervention Description
Participants will receive 5 vaccines of personalized RNA vaccine (HIVACAR01), 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
Participants will receive 5 vaccines of placebo of HIVACAR01, 2 doses of 10-1074 antibodies and 3 doses of romidepsin
Primary Outcome Measure Information:
Title
Grade 3 or above severe local , systemic, clinical or laboratory adverse event t
Description
Local adverse events may be pain, cutaneous reactions including induration and systemic emperature, chills, headache, nausea, vomiting, malaise, and myalgia. Clinical and laboratory must be confirmed at examination or on repeat testing respectively. Any adverse event attributable to the combination therapy leading to discontinuation of the study treatmen
Time Frame
12 days (28 days after each inmuisation)
Secondary Outcome Measure Information:
Title
Proportion of participants who maintain an undetectable viral load
Description
defined as a viral load below the threshold of 50 copies/ml
Time Frame
12 weeks (after discontinuation of antiretroviral therapy)
Title
Percentage of participants with control of viral load below detectable level
Time Frame
24 weeks (after discontinuation of antiretroviral therapy)
Title
Change from baseline in total proviral HIV-1 DNA per 10^6 CD4+ T cells.
Time Frame
up to 51 weeks
Title
Change from baseline in integrated proviral HIV-1 DNA per 10^6 CD4+ T cells.
Time Frame
up to 51 weeks
Title
Change from baseline in HIV-1 transcription.
Description
According to CA US HIV-1 RNA measured in unfractionated CD4+ T cells
Time Frame
up to 39 weeks
Title
Change in plasma HIV-1 RNA from baseline
Time Frame
up to 39 weeks
Title
Breadth and magnitude of CD4+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline.
Time Frame
up to 27 weeks
Title
Breadth and magnitude of CD8+ HIV-specific T cell responses measured by IFN-gamma ELISPOT compared with baseline.
Time Frame
up to 27 weeks
Title
Breadth and magnitude of CD4+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline.
Time Frame
up to 27 weeks
Title
Breadth and magnitude of CD8+ HIV-specific T cell responses measured by Intra-cellular cytokine staining-ICS in the study arms as compared with baseline.
Time Frame
up to 27 weeks
Title
Change from baseline in CD8+ T-cell HIV suppressive capacity.
Time Frame
up to 51 weeks
Title
Change from baseline in T cell activation markers
Time Frame
up to 29 weeks
Title
Change from baseline in T cell activation markers
Time Frame
3 weeeks
Title
Change from baseline in T cell activation markers
Time Frame
up to 24 weeks
Title
Change from baseline in T cell subset distribution
Time Frame
up to 29 weeks
Title
Change from baseline in T cell subset distribution
Time Frame
14 weeks
Title
Change from baseline in T cell subset distribution
Time Frame
up to 27 weeks
Title
Change from baseline in PD-1 expression
Time Frame
up to 51 weeks
Title
Evaluate fecal microbiome
Time Frame
baseline and at week 14
Title
Characterise viral escape from vaccine-induced immune T cell responses
Description
Comparison of viral sequences pre-cART and rebounding after cART interruption
Time Frame
up to 51 weeks
Title
Analysis of changes in sensitivity to neutralisation by 10-1074 of rebounding viruses after cART interruption to identify neutralisation escape mutants.
Time Frame
up to 51 weeks
Title
To evaluate mRNA expression profiles in whole PBMC at baseline
Time Frame
at first romidepsin administration and 14 and 26 weeks after first romidepsin administration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Between ≥ 18 to <60 years of age
Voluntarily signed informed consent
Male, or female with negative pregnancy test prior to enrolment
Proven HIV-1 infection (with positive antibodies against HIV-1 and a detectable plasma HIV-1 RNA before cART)
Must be on stable treatment with cART for at least 18 months (cART is defined as an antiretroviral regimen consisting of at least three registered antiretroviral agents; periods of mono/dual antiretroviral therapy if not first time therapy and confirmed viral suppression during these periods of mono/dual therapy are permitted)
Nadir CD4+ cell counts must be above or equal to 350 cells/µl, 2-3 occasional determinations below 350 cells/μl are allowed.
Current CD4+ cell count must be at least 450 cells/µl
HIV-RNA must be below 50 copies/ mL for the last 12 months prior to inclusion, during at least two measurements (occasional so called 'blips' up to 500 copies/mL are permitted)
If male or female of childbearing potential willing to take correct contraceptive measures:
If heterosexually active female; using an effective method of contraception from 14 days prior to the first vaccination until at least 12 weeks after the last vaccination; all female volunteers must be willing to undergo urine or serum pregnancy tests at time points specified in the Schedule of Procedures.
If heterosexually active male; willing to use an effective method of contraception or agree on the use of an effective method of contraception by his partner from the day of the first vaccination until 12 weeks after the last vaccination.
If sexually active, willing to use a reliable method of reducing the risk of transmission to their sexual partners during treatment interruption (which could include pre-exposure prophylaxis [PrEP] for their sexual partners)
Exclusion Criteria:
Treatment with a non-cART regimen of antiretroviral agents prior to the start of any antiretroviral regimen
History of a CDC class C event (see Appendix IV)
Women of childbearing potential with a positive pregnancy test, or participants (male or female) who wish to plan a pregnancy during the trial period.
Active opportunistic infection, or any active infection or malignancy within 30 days prior to screening visit
Therapy with immunomodulatory agents, including cytokines (e.g. IL2) and gamma globulin, or cytostatic chemotherapy within 90 days prior to screening visit
Use of anti-coagulant medication
Use of any investigational drug during the 90 days prior to study entry
Previous antiretroviral therapy failure and/or mutations conferring genotypic resistance to antiretroviral therapy
Participants with severe cardiovascular diseases or long QT interval
Active hepatitis C virus
Hepatitis B infection
Treatment with strong inhibitors or inducers of CYP3A4, except protease inhibitors for HIV treatment (see protocol section 5.7); if in treatment of protease inhibitors for HIV not willing to change inhibitor protease for an integrase inhibitor during the study.
Any known allergy or intolerance to any of the study drugs or excipient
Protein egg allergy
Known past history of clinical Epstein-Barr Virus (EBV) infection or recurrent herpes zoster
Hematologic abnormalities ≥Grade 1
Potassium or magnesium levels outside the upper limit of normal (ULN) and lower limit of normal (LLN)
History of autoimmune disorders as multiple sclerosis.
Any other condition which, in the opinion of the investigator, may interfere with the evaluation of the study objectives
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Felipe Garcia, MD
Phone
+93.227.54.00
Email
fgarcia@clinic.cat
First Name & Middle Initial & Last Name or Official Title & Degree
Florencia Etcheverry
Phone
+93.227.54.00
Email
MFETCHEV@clinic.cat
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Learn more about this trial
Evaluating a Combination of Immune-based Therapies to Achieve a Remission of HIV Infection
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