- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04985760
Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy (NETI)
Safety, Tolerability and Immunogenicity of Recombinant HIV Envelope Protein VRC-HIVRGP096-00-VP (Trimer 4571) Vaccine, in HIV-1 Infected Adults on Suppressive ART
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The immune system is composed of special cells, proteins, tissues, and organs that protect against germs and microorganisms and is the body's defense against infections. Antibodies are a type of protein that helps the body fight infection and are usually made by a person's own immune system. A type of antibody that can recognize and block many types of HIV from entering healthy cells are called broadly neutralizing antibodies, or 'bnAbs', and may also activate other immune cells to help destroy HIV-infected cells. Research has shown that people with HIV who develop bnAbs against the virus are better able to control the infection. While the immune systems of some people with HIV show signs of early bnAb production, only a small percentage of people with HIV naturally develop bnAbs.
Approximately 32 participants will be sequentially enrolled and randomized 3:1 by chance like rolling dice to receive either the Trimer 4571 vaccine or a placebo vaccine that does not contain Trimer 4571.
Participants will be asked to attend 11 study visits over a period of approximately 50 weeks and receive 3 doses of their assigned study vaccine: one at Entry, one at Week 8 and one at Week 20. Researchers will compare the results from participants who get the Trimer 4571 vaccine with results from participants who get the placebo vaccine. Participants, the researchers and the clinic staff will not know which vaccine participants are getting.
After Week 20, participants will be followed for 24 additional weeks with study visits and tests to monitor their health and safety and to see how the study vaccine affects the immune system and the virus.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Madhu Choudhary, MD
- Phone Number: 412-383-1675
- Email: mac529@pitt.edu
Study Contact Backup
- Name: Stacey Edick, PA-C
- Phone Number: 412-383-1482
- Email: edicksm2@upmc.edu
Study Locations
-
-
Ohio
-
Columbus, Ohio, United States, 43210
- Recruiting
- AIDS Clinical Trials Unit/The Ohio State University
-
Contact:
- Lindsay M Summers, BS, MPH
- Phone Number: 614-293-8529
- Email: lindsay.summers@osumc.edu
-
Contact:
- Lucia J Niermann, BS
- Phone Number: 614-293-3550
- Email: lucia.niermann@osumc.edu
-
Principal Investigator:
- Susan L Koletar, MD
-
Sub-Investigator:
- Carlos D Malvestutto, MD, MPH
-
Sub-Investigator:
- William Maher, MD
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, United States, 15213
- Recruiting
- University of Pittsburgh
-
Contact:
- Sherri Karas
- Phone Number: 412-383-1313
- Email: schesx@upmc.edu
-
Sub-Investigator:
- Sharon Riddler, MD
-
Sub-Investigator:
- Deborah McMahon, MD
-
Sub-Investigator:
- Bernard Macatangay, MD
-
Principal Investigator:
- Madhu Choudhary, MD
-
Sub-Investigator:
- Ken Ho, MD
-
Sub-Investigator:
- Stacey Edick, PA-C
-
Contact:
- Jamie Fullerton
- Phone Number: 412-383-1675
- Email: idelucaj@upmc.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- HIV-1 infection, documented by any FDA-approved assay. NOTE: The term 'licensed' refers to a US FDA approved kit, which is required for all investigational new drug (IND) studies.
- Receiving continuous antiretroviral therapy (ART) for at least 24 months (defined as no interruptions longer than 30 consecutive days) and with no changes in the components of the ART for at least 8 weeks prior to study entry. A change in formulation (for example tenofovir disaproxil fumarate to tenofovir alafenamide) will not be considered a change in ART.
- Screening CD4+ cell count ≥200cells/mm3 obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
Plasma HIV-1 RNA levels < 50 copies/ml for at least 24 months on ART prior to study entry using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent. Participants must have at least one documented HIV-1 RNA < 50 copies/ml within 12 months prior to study entry. All available HIV-1 RNA measurements must be < 50 copies/ml during the 24 months prior to study entry except as allowed by the following note.
NOTE: Unconfirmed plasma HIV-1 RNA > 50 copies/ml but <200 copies/mL is allowed if followed by a subsequent value < 50 copies/ml.
- Screening HIV-1 RNA levels <50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 60 days prior to entry.
- Men and women ages > 18 years.
The following laboratory values obtained within 60 days prior to entry:
- Hemoglobin ≥10 g/dL
- Absolute neutrophil count (ANC) ≥1000/mm3
- Platelet count ≥100,000/mm3
- Creatinine ≤ 1.5x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (SGPT) ≤2.5x ULN
- Ability and willingness of participant to provide informed consent.
- In the opinion of the investigator, no medical, mental health or other condition that precludes participation.
- For persons who can become pregnant, negative serum or urine pregnancy test within 48 hours prior to entry by any US clinic or laboratory that has a CLIA certification or its equivalent, or is using a point-of-care (POC)/ CLIA-waived test. Persons who can become pregnant include women who have not been post-menopausal for at least 12 consecutive months, (i.e., who have had menses within the preceding 12 months) or women who have not undergone surgical sterilization (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation or salpingectomy). Self- report is acceptable documentation of menopause and sterilization.
- All participants must agree not to participate in the conception process (eg, active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the participant/partner must use at least one reliable form of contraception (condoms, with or without a spermicidal agent; a diaphragm or cervical cap with spermicide; an IUD; or hormone-based contraceptive), while receiving study treatment and for 12 weeks following the final study vaccine.
Exclusion Criteria:
- Known to have been started on antiretroviral therapy within 3 months of the presumed or known date of first acquiring HIV-1 infection; i.e., treated during acute HIV-1 infection
- Currently breastfeeding or pregnant
- Known allergy/sensitivity or any hypersensitivity to components of study vaccine or their formulation.
- Known chronic inflammatory conditions such as, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune hepatitis, myositis, or myopathy.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- Serious medical illness that requires systemic treatment and/or hospitalization within 30 days prior to entry.
Use of systemic immunomodulators (e.g., interleukins, interferons, Cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.
NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone ≤10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids, or topical imiquimod will not be excluded.
- Receipt of any investigational HIV immunotherapy or HIV therapeutic vaccination within 12 months prior to study entry.
- History of positive HCV antibody with detectable HCV RNA in plasma within 48 Weeks prior to study entry. NOTE: Persons with positive HCV Ab but negative plasma HCV RNA are allowed to participate. Sites must document negative HCV RNA within 24 weeks of study entry.
- Treatment for hepatitis C within 6 months prior to study entry.
- History of positive HBsAg within 48 weeks prior to study entry.
- History of severe reaction or anaphylaxis to prior vaccinations.
- Body Mass Index >40kg/m2.
- Receipt of Blood products or immune globulins within 16 weeks prior to Enrollment as per protocol section 5.3.2.
- Receipt of Live attenuated vaccines within 4 weeks prior to enrollment.
- Current allergen immunotherapy with antigen injections, unless on maintenance schedule.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Randomized Blinded Trimer 4571 Vaccine 100mcg
Six (6) participants will receive Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant as a 1ml intramuscular injection at Day 0, Week 8 and Week 20.
|
Investigational vaccine composed of Trimer 4571 100mcg, alum (aluminum hydroxide suspension) adjuvant 500mcg, and phosphate buffered saline diluent
Other Names:
|
Placebo Comparator: Randomized Blinded Placebo for Trimer 4571 Vaccine 100mcg
Two (2) participants will receive the placebo control for Trimer 4571 vaccine 100mcg as a 1ml intramuscular injection at Day 0, Week 8 and Week 20.
|
Volume matched control for Trimer 4571 vaccine 100mcg
Other Names:
|
Experimental: Randomized Blinded Trimer 4571 Vaccine 500mcg
Eighteen (18) participants will receive Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant as a 1.1ml intramuscular injection at Day 0, Week 8 and Week 20.
|
Investigational vaccine composed of Trimer 4571 500mcg, alum (aluminum hydroxide suspension) adjuvant 500mcg, and phosphate buffered saline diluent
Other Names:
|
Placebo Comparator: Randomized Blinded Placebo for Trimer 4571 Vaccine 500mcg
Six (6) participants will receive the placebo control for Trimer 4571 vaccine 500mcg as a 1.1ml intramuscular injection at Day 0, Week 8 and Week 20.
|
Volume matched control for Trimer 4571 vaccine 500mcg
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and tolerability of three vaccinations of Trimer 4571 vaccine in adults with HIV on suppressive ART
Time Frame: Day 0 through Week 44
|
The proportion of participants experiencing at least one Grade 3 or higher adverse event will be summarized within and across the Trimer 4571 vaccine 100mcg, Trimer 4571 vaccine 500mcg and placebo control vaccine groups.
The number of adverse events in each group will also be summarized by severity, body system, and relationship to study vaccine using frequencies, percent, and 95% confidence intervals.
|
Day 0 through Week 44
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Immunogenicity of three vaccinations of Trimer 4571 vaccine in adults with HIV on suppressive ART
Time Frame: Baseline and Week 22
|
Comparison of the change in the serum ID50 neutralization titer of BG505.W6M.C2 virus between Trimer 4571 vaccine 100mcg, Trimer 4571 vaccine 500mcg, and placebo control vaccine.
Vaccine responders will be as defined by either (i) 4-fold increase in neutralization titer from pre-vaccination to at least one virus in the curated virus panel at any protocol-specified time point post vaccination and/or (ii) Evidence of BG505.W2 neutralization at any protocol-specified time point post vaccination.
|
Baseline and Week 22
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Madhu Choudhary, MD, University of Pittsburgh
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Sexually Transmitted Diseases, Viral
- Sexually Transmitted Diseases
- Lentivirus Infections
- Retroviridae Infections
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Urogenital Diseases
- Genital Diseases
- HIV Infections
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Immunologic Factors
- Gastrointestinal Agents
- Adjuvants, Immunologic
- Antacids
- Vaccines
- Aluminum Hydroxide
- Aluminum sulfate
Other Study ID Numbers
- DAIDS-ES 38763
- U01AI152969 (U.S. NIH Grant/Contract)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on HIV Infections
-
University of MinnesotaWithdrawnHIV Infections | HIV/AIDS | Hiv | AIDS | Aids/Hiv Problem | AIDS and InfectionsUnited States
-
University of California, San DiegoUniversity of California, Los Angeles; University of Southern California; California... and other collaboratorsCompleted
-
Gérond'ifRecruiting
-
University of California, DavisCompleted
-
University of California, San DiegoNational Center for Complementary and Integrative Health (NCCIH)CompletedHIV PositiveUnited States
-
University of ChicagoUniversity of Athens; National Development and Research Institutes, Inc.Completed
-
HIV Prevention Trials NetworkNational Institute on Drug Abuse (NIDA); National Institute of Allergy and...CompletedHIV PositiveIndonesia, Ukraine, Vietnam
-
University of ZimbabweCompleted
-
Florida International UniversityCompleted
-
Boston Children's HospitalNational Institute on Minority Health and Health Disparities (NIMHD)Completed
Clinical Trials on Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant
-
National Institute of Allergy and Infectious Diseases...RecruitingHealthy VolunteerUnited States
-
National Institute of Allergy and Infectious Diseases...CompletedHuman Immunodeficiency Virus (HIV) | Human Immunodeficiency Virus PreventionUnited States
-
U.S. Army Medical Research and Development CommandGlaxoSmithKline; Walter Reed Army Institute of Research (WRAIR)Completed
-
U.S. Army Medical Research and Development CommandCompleted