NCT05781542

Clinical Trial to Evaluate the Safety and Immunogenicity of Synthetic DNAs Encoding NP-GT8 and IL-12, With or Without a TLR-agonist-Adjuvanted HIV Env Trimer 4571 Boost, in Adults Without HIV

Completed Phase 1 Results posted Last updated 14 November 2025

What this trial tests

Phase 1 trial testing sD-NP-GT8 DNA in HIV Infections in 46 participants. Completed in 14 April 2025.

Timeline

10 April 2023

Primary endpoint
2 October 2024

14 April 2025

Quick facts

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	single group
Masking	none
Primary purpose	prevention
Enrollment	46
Start date	10 April 2023
Primary completion	2 October 2024
Estimated completion	14 April 2025
Sites	8 locations across South Africa, United States

Drugs / interventions tested

• sD-NP-GT8 DNA — full drug profile →
• sD-NP-GT8 DNA — full drug profile →
• IL-12 DNA — full drug profile →
• IL-12 DNA — full drug profile →
• Trimer 4571 — full drug profile →
• 3M-052-AF — full drug profile →
• Alum (Alum) — full drug profile →

Conditions studied

• HIV Infections — all drugs for HIV Infections →

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Who can join

Adults 18 to 55, any sex, with HIV Infections. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Reporting Local Solicited Adverse Events Signs and Symptoms: Pain and/or Tenderness Primary · Measured through 7 days following vaccine administration for INO-6172 alone and 14 days following vaccine administration for Trimer 4571 + 3M-052-AF/Alum

Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

Group	Value	95% CI
Group T1	3
Group T2	9
Group T3	4
Group T1	6
Group T2	8
Group T3	10
Group T1	1
Group T2	1
Group T3	1
Group T1	0
Group T2	0
Group T3	3

Number of Participants Reporting Local Solicited Adverse Events Signs and Symptoms: Erythema and/or Induration Primary · Measured through 7 days following vaccine administration for INO-6172 alone and 14 days following vaccine administration for Trimer 4571 + 3M-052-AF/Alum

Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

Erythema/Redness

Group	Value	95% CI
Group T1	8
Group T2	13
Group T3	13
Group T1	1
Group T2	4
Group T3	5
Group T1	1
Group T2	1
Group T3	0
Group T1	0
Group T2	0
Group T3	0

Induration/Swelling

Group	Value	95% CI
Group T1	8
Group T2	16
Group T3	16
Group T1	2
Group T2	2
Group T3	2
Group T1	0
Group T2	0
Group T3	0
Group T1	0
Group T2	0
Group T3	0

Erythema and/or Induration

Group	Value	95% CI
Group T1	8
Group T2	13
Group T3	13
Group T1	1
Group T2	4
Group T3	5
Group T1	1
Group T2	1
Group T3	0
Group T1	0
Group T2	0
Group T3	0

Number of Participants Reporting Unsolicited Adverse Events (AEs), by Severity Grade Primary · Measured through 7 days following vaccine administration for INO-6172 alone and 14 days following vaccine administration for Trimer 4571 + 3M-052-AF/Alum

The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm and severity grade. The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm and severity grade. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)

Malaise and/or fatigue

Group	Value	95% CI
Group T1	7
Group T2	10
Group T3	4
Group T1	2
Group T2	5
Group T3	5
Group T1	1
Group T2	2
Group T3	4
Group T1	0
Group T2	1
Group T3	5

Myalgia

Group	Value	95% CI
Group T1	9
Group T2	13
Group T3	5
Group T1	1
Group T2	5
Group T3	7
Group T1	0
Group T2	0
Group T3	2
Group T1	0
Group T2	0
Group T3	4

Headache

Group	Value	95% CI
Group T1	7
Group T2	11
Group T3	5
Group T1	2
Group T2	4
Group T3	7
Group T1	1
Group T2	2
Group T3	1
Group T1	0
Group T2	1
Group T3	5

Nausea

Group	Value	95% CI
Group T1	9
Group T2	14
Group T3	9
Group T1	1
Group T2	3
Group T3	6
Group T1	0
Group T2	1
Group T3	3
Group T1	0
Group T2	0
Group T3	0

Chills

Group	Value	95% CI
Group T1	10
Group T2	14
Group T3	5
Group T1	0
Group T2	4
Group T3	8
Group T1	0
Group T2	0
Group T3	2
Group T1	0
Group T2	0
Group T3	3

Arthralgia

Group	Value	95% CI
Group T1	9
Group T2	16
Group T3	7
Group T1	1
Group T2	2
Group T3	5
Group T1	0
Group T2	0
Group T3	4
Group T1	0
Group T2	0
Group T3	2

Max. Systemic Symptoms

Group	Value	95% CI
Group T1	6
Group T2	9
Group T3	3
Group T1	3
Group T2	4
Group T3	5
Group T1	1
Group T2	4
Group T3	3
Group T1	0
Group T2	1
Group T3	7

Temperature

Group	Value	95% CI
Group T1	10
Group T2	17
Group T3	13
Group T1	0
Group T2	1
Group T3	3
Group T1	0
Group T2	0
Group T3	2
Group T1	0
Group T2	0
Group T3	0

Number of Participants Reporting Unsolicited Adverse Events (AEs), by Severity Grade Primary · Measured for 30 days after any receipt of study vaccination

The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm and severity grade. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)

Mild

Group	Value	95% CI
Group T1	0
Group T2	2
Group T3	3

Moderate

Group	Value	95% CI
Group T1	5
Group T2	6
Group T3	9

Severe

Group	Value	95% CI
Group T1	0
Group T2	0
Group T3	1

Potentially life-threatening

Group	Value	95% CI
Group T1	0
Group T2	0
Group T3	0

Number of Participants Reporting Medically Attended Adverse Events (MAAEs), by Severity Grade Primary · Measured through Month 12 following any receipt of study products

The number (percentage) of Participants Reporting Medically Attended Adverse Events (MAAEs) was summarized by arm and severity grade

Mild

Group	Value	95% CI
Group T1	0
Group T2	0
Group T3	0

Moderate

Group	Value	95% CI
Group T1	5
Group T2	4
Group T3	7

Severe

Group	Value	95% CI
Group T1	0
Group T2	0
Group T3	0

Potentially life-threatening

Group	Value	95% CI
Group T1	0
Group T2	0
Group T3	0

Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation Primary · Measured through Month 12 following any receipt of study products

The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm

Group	Value	95% CI
Group T1	1
Group T2	0
Group T3	0
Group T1	0
Group T2	1
Group T3	0
Group T1	9
Group T2	17
Group T3	18

Number of Participants With Early Study Termination and Reason for Early Study Termination Primary · Measured through Month 12 following any receipt of study products

The number (percentage) of participants with early study termination and reason for early study termination was summarized by arm

Group	Value	95% CI
Group T1	1
Group T2	0
Group T3	1
Group T1	9
Group T2	18
Group T3	17

Adverse events — posted to ClinicalTrials.gov

Time frame: The AE reporting period for this study comprises the entire study period for each individual participant (from the participant's study enrollment until his or her study completion or discontinuation), up to 18 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group T1

Serious: 0/10 (0%)

Deaths: 0/10

Group T2

Serious: 0/18 (0%)

Deaths: 0/18

Group T3

Serious: 0/18 (0%)

Deaths: 0/18

Other adverse events (64 terms — click to expand)

Reaction	System	Group T1	Group T2	Group T3
Injection site pain (Solicited)	General disorders	—	—	—
Malaise (Solicited)	General disorders	—	—	—
Chills (Solicited)	General disorders	—	—	—
Myalgia (Solicited)	Musculoskeletal and connective tissue disorders	—	—	—
Headache (Solicited)	Nervous system disorders	—	—	—
Arthralgia (Solicited)	Musculoskeletal and connective tissue disorders	—	—	—
Nausea (Solicited)	Gastrointestinal disorders	—	—	—
Injection site erythema (Solicited)	General disorders	—	—	—
Body temperature increased (Solicited)	Investigations	—	—	—
Injection site swelling (Solicited)	General disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Blood creatinine increased	Investigations	—	—	—
Neutrophil count decreased	Investigations	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Lymph node pain	Blood and lymphatic system disorders	—	—	—
Arrhythmia	Cardiac disorders	—	—	—
Tachycardia	Cardiac disorders	—	—	—
Blepharitis	Eye disorders	—	—	—
Dental caries	Gastrointestinal disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Gastritis	Gastrointestinal disorders	—	—	—
Gastrooesophageal reflux disease	Gastrointestinal disorders	—	—	—
Cyst	General disorders	—	—	—
Injection site pruritus	General disorders	—	—	—
Seasonal allergy	Immune system disorders	—	—	—
Abscess limb	Infections and infestations	—	—	—
Bronchitis	Infections and infestations	—	—	—
Conjunctivitis	Infections and infestations	—	—	—
Gastroenteritis viral	Infections and infestations	—	—	—
Gingivitis	Infections and infestations	—	—	—
Herpes simplex	Infections and infestations	—	—	—
Impetigo	Infections and infestations	—	—	—
Norovirus infection	Infections and infestations	—	—	—
Oropharyngeal gonococcal infection	Infections and infestations	—	—	—
Pharyngitis	Infections and infestations	—	—	—
Pharyngitis streptococcal	Infections and infestations	—	—	—
Staphylococcal infection	Infections and infestations	—	—	—
Subcutaneous abscess	Infections and infestations	—	—	—
Syphilis	Infections and infestations	—	—	—
Tooth abscess	Infections and infestations	—	—	—

Data from ClinicalTrials.gov NCT05781542 adverse events section.

Sponsor's own description

This is an open-label study to examine the safety and immunogenicity of synthetic DNAs encoding NP-GT8 and IL-12 with or without a TLR-agonist-adjuvanted Env Trimer 4571 boost in adults without HIV. The primary hypothesis is that vaccination with this recombinant DNA vaccine encoding a germline-targeting epitope followed by a trimeric protein boost will elicit VRC01-class B-cell responses as well as antigen-specific T-cell responses.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV-workshop report.
   Maciel M, Amara RR, Bar KJ, Crotty S, et al · · 2024 · cited 12× · PMID 38383616 · DOI 10.1038/s41541-024-00818-y