Clinical trial NCT06665646: Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV
Official title: A Phase 1 Open-label, Non-randomized, Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in the HVTN706/MOSAICO Study and Remain Without HIV
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: HIV Infections
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2024-10-30
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The clinical schedule will consist of 3 injections of CD40.HIVRI.Env (VRIPRO) at weeks 0, 4, and 24.40 volunteers without HIV and in overall good health, aged 18 to 60 years, who previously participated in the HVTN 706/MOSAICO trial.


Eligibility criteria: Inclusion Criteria:

1. Formerly participated in HVTN-706 - the MOSAICO study as active vaccine arm or placebo recipient (those enrolled in the active vaccine arm of MOSAICO must have received all 4 vaccinations according to the MOSAICO protocol).
2. Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
3. 18 to 60 years old, inclusive, on day of enrollment.
4. Available for clinic follow-up through the last clinic visit, willing to undergo FNA, and willing to be contacted 12 months after the last study-product administration.
5. Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 318 (Protocol Safety Review Team ) PSRT are required prior to enrollment into HVTN 318. Previous enrollment in HVTN 706 (MOSAICO) study is not a barrier to enrollment in HVTN 318, per inclusion criteria 1.
6. In good general health according to the clinical judgment of the site investigator.
7. Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
8. Agrees to discuss their potential for HIV acquisition and agrees to prevention counseling.
9. Hemoglobin (Hgb):

   * ≥ 13.0 g/dL for cisgender AMAB volunteers or for volunteers who have been on masculinizing hormone therapy for more than 6 consecutive months
   * ≥ 12.0 g/dL for AMAB volunteers who have been on feminizing hormone therapy for more than 6 consecutive months
   * For volunteers who have been on gender-affirming hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
10. White blood cell (WBC) count = 2,500 to 12,000/mm3 (WBC over 12,000/mm3 is not exclusionary if further evaluation shows general good health and if PSRT approval is granted).
11. Platelets = 125,000 to 550,000/mm3.
12. Alanine aminotransferase (ALT) \< 2.5 x upper limit of institutional reference range.
13. Serum creatinine ≤ 1.1 x upper limit of normal (ULN) based on the institutional normal range.
14. Systolic blood pressure of 90 to \< 140 mmHg and diastolic blood pressure of 50 to \< 90 mmHg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mmHg systolic and 90 mmHg diastolic. A single measurement ≥ 160 systolic mmHg or 100 mmHg diastolic during the current study evaluation is exclusionary.
15. Negative HIV test results by one of the following options:

    For participants who received study product under HVTN 706 (MOSAICO)
    * A negative result from a HVTN HIV Diagnostic Testing Laboratory within 14 days prior to enrollment; or
    * A negative result from a non-HVTN laboratory following the external guidance for non-HVTN laboratories within 14 days prior to enrollment

    For participants who received placebo under HVTN 706 (MOSICO)
    * A negative European Conformity (CE)-marked enzyme immunoassay (EIA)
    * A chemiluminescent microparticle immunoassay (CMIA)
    * A negative result on 2 HIV rapid tests (one of these rapid tests must be CE-marked)
16. Negative for anti-Hepatitis C virus (HCV) Abs (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies (Abs) are detected.
17. Negative for Hepatitis B surface antigen (Ag).

Exclusion Criteria:

1. Body mass index (BMI) ≥ 40. Enrollment of individuals with BMI ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT approval.
2. Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤ 8% within the last 6 months) or a history of isolated gestational diabetes are not exclusionary. Enrollment of individuals with Type 2 DM that is well controlled on hypoglycemic agent(s) may be considered by the PSRT on a case-by-case basis, provided that the HgbA1c is ≤ 8% within the last 6 months (sites may draw these at screening).
3. Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded), with the exception of the HVTN 706 (MOSAICO) vaccine regimen as per Inclusion Criteria #1.
4. Receipt of non-HIV investigational vaccine(s) received within the last 1 year. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA or World Health Organization (WHO) Emergency Use Listing (EUL), or if outside the US, by the national Regulatory Authority (RA) authorizing this clinical trial.
5. Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, such as glucocorticoid use, ≥ prednisone 10 mg/day within 3 months prior to enrollment.
6. Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
7. Previous receipt of VRC01 monoclonal antibody (mAb).
8. Receipt of any vaccine within 4 weeks prior to enrollment
9. Initiation of Ag-based immunotherapy for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.
10. Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life of more than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
11. Use of injectable long-acting Cabotegravir within 18 months prior to enrollment.
12. Serious adverse reactions to any vaccine, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a participant who had a non-anaphylactic adverse reaction to pertussis vaccine as a child.)
13. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
14. Idiopathic urticaria within the past year.
15. Bleeding disorder diagnosed by a clinician that would make study procedures a contraindication.
16. History of seizure(s) within the past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years.
17. Asplenia or functional asplenia.
18. Active duty and reserve US military personnel.
19. Any other chronic or clinically significant condition that, in the clinical judgment of the investigator, would jeopardize the safety or rights of the study participant, including but not limited to: clinically significant forms of substance use or alcohol use disorder(s), serious psychiatric disorders, any suicide attempt within the past 1 year (if between 1 and 2 years, consult PSRT for approval), or cancer that, in the clinical judgement of the site investigator, has potential for recurrence (excluding basal cell carcinoma).
20. Asthma is excluded if the participant has ANY of the following:

    * Required either oral or parenteral corticosteroids for an exacerbation 2 or more times within the past year; OR
    * Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or coexisting conditions unrelated to asthma); OR
    * Uses a short-acting rescue inhaler more than 2 days per week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR
    * Uses medium- to high-dose inhaled corticosteroids (\> 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist \[LABA\]); OR
    * Uses more than 1 medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than 1 medication for maintenance therapy daily for greater than 2 years requires PSRT approval.
21. A participant with a history of a potential immune-mediated medical condition (PIMMC), either active or remote. Specific examples are listed in Appendix F (AESI Index). Not exclusionary: 1) Remote history of Bell's palsy (\> 2 years ago) not associated with other neurologic symptoms and 2) mild psoriasis or other mild, uncomplicated, localized, or dermatologic condition that does not require ongoing systemic treatment.
22. History of allergy to local anesthetic (Novocaine, Lidocaine).
23. Volunteer who is breastfeeding/chestfeeding.
24. Investigator concern for difficulty with venous access based on clinical history and physical examination. For example, persons with a history of intravenous drug use or substantial difficulty with previous blood draws.

Primary outcomes:
measure: Local signs and symptoms will be collected for a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)
timeFrame: For a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)
measure: Systemic reactogenicity signs and symptoms will be collected
timeFrame: For a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)
measure: Number of SAEs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product
timeFrame: 30 days after receipt of study vaccination up to 1 year following study product
measure: Number of MAAEs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product
timeFrame: 30 days after receipt of study vaccination up to 1 year following study product
measure: Number of AESIs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product
timeFrame: 30 days after receipt of study vaccination up to 1 year following study product
measure: Number of AEs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product
timeFrame: 30 days after receipt of study vaccination up to 1 year following study product
measure: Response rate of HIV-1-specific serum IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA) in MOSAICO regimen recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of HIV-1-specific serum IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA) in MOSAICO regimen recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of HIV-1-specific serum IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA in MOSIACO regimen recipients
timeFrame: 2 weeks receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of HIV-1-specific serum IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA in MOSIACO regimen recipients
timeFrame: 2 weeks receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
Secondary outcomes:
measure: Response rate of serum HIV-1-specific IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA) in MOSAICO regiment recipients
timeFrame: 2 weeks after the receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum HIV-1-specific IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA) in MOSAICO regiment recipients
timeFrame: 2 weeks after the receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum-HIV-1 specific IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA in MOSAICO regimen recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum-HIV-1 specific IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA in MOSAICO regimen recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum HIV-1 specific IgG3 binding antibodies against autologous V1V2 antigens as assessed by BAMA in MOSAICO participants
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum HIV-1 specific IgG3 binding antibodies against autologous V1V2 antigens as assessed by BAMA in MOSAICO participants
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum HIV-1 specific IgG3 binding antibodies against heterologous V1V2 antigens as assessed by BAMA in MOSAICO participants
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum HIV-1 specific IgG3 binding antibodies against heterologous V1V2 antigens as assessed by BAMA in MOSAICO participants
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum HIV-1 specific IgG binding antibodies against autologous Env antigens as assessed by BAMA in MOSAICO recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum HIV-1 specific IgG binding antibodies against autologous Env antigens as assessed by BAMA in MOSAICO recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum HIV-1 specific IgG binding antibodies against heterologous Env antigens as assessed by BAMA in MOSAICO recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum HIV-1 specific IgG binding antibodies against heterologous Env antigens as assessed by BAMA in MOSAICO recipients
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum Ab neutralization of autologous HIV-1 strains as measured by the TZM-bl assay in MOSAICO recipients
timeFrame: 2 weeks after receipt of the CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum Ab neutralization of autologous HIV-1 strains as measured by the TZM-bl assay in MOSAICO recipients
timeFrame: 2 weeks after receipt of the CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum Ab neutralization of heterologous HIV-1 strains as measured by TZM-bl assay in MOSAICO recipients
timeFrame: 2 weeks after receipt of the CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of serum Ab neutralization of heterologous HIV-1 strains as measured by TZM-bl assay in MOSAICO recipients
timeFrame: 2 weeks after receipt of the CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of CD4+ and CD8+ T-cell responses as assessed by intracellular cytokine staining, Epimax, or other assays, as needed, in MOSAICO regimen recipients
timeFrame: 2 weeks after receipt of the CD40.HIVRI.Env (VRIPRO) regimen
measure: Magnitude of CD4+ and CD8+ T-cell responses as assessed by intracellular cytokine staining, Epimax, or other assays, as needed, in MOSAICO regimen recipients
timeFrame: 2 weeks after receipt of the CD40.HIVRI.Env (VRIPRO) regimen
measure: Response rate of serum HIV-1 specific binding antibodies as assessed by BAMA
timeFrame: 2 weeks after each vaccination in MOSAICO placebo recipients
measure: Magnitude of serum HIV-1 specific binding antibodies as assessed by BAMA
timeFrame: 2 weeks after each vaccination in MOSAICO placebo recipients
measure: Response rate of serum neutralization of autologous and heterologous HIV-1 strains as measured by the TZM-bl assay
timeFrame: 2 weeks after each vaccination in MOSAICO placebo recipients
measure: Magnitude of serum neutralization of autologous and heterologous HIV-1 strains as measured by the TZM-bl assay
timeFrame: 2 weeks after each vaccination in MOSAICO placebo recipients
measure: Response rate of antibody-dependent cellular cytotoxicity (ADCC)
timeFrame: at baseline and 2 weeks after the last vaccination in MOSAICO and placebo recipients
measure: Magnitude of antibody-dependent cellular cytotoxicity (ADCC)
timeFrame: at baseline and 2 weeks after the last vaccination in MOSAICO and placebo recipients
measure: Response rate of antibody-dependent cellular phagocytosis (ADCP)
timeFrame: at baseline and 2 weeks after the last vaccination in MOSAICO and placebo recipients
measure: Magnitude of antibody-dependent cellular phagocytosis (ADCP)
timeFrame: at baseline and 2 weeks after the last vaccination in MOSAICO and placebo recipients
measure: Magnitude of Env-specific binding Abs assessed by the slope of BAMA titers
timeFrame: weeks 26 and 48
measure: Frequency of total memory B cells and vaccine-specific B cell receptors
timeFrame: 2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Bridge HIV CRS
state: California
city: Decatur
country: United States
facility: The Hope Clinic of the Emory Vaccine Center CRS
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
state: Massachusetts
city: New York
country: United States
facility: Columbia P&S CRS
state: New York
city: Philadelphia
country: United States
facility: Penn Prevention CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Vaccine (VV) CRS
state: Tennessee
city: Seattle
country: United States
facility: Seattle Vaccine and Prevention CRS
state: Washington
Study officials:
References: