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Trial registered on ANZCTR


Registration number
ACTRN12624000064505
Ethics application status
Approved
Date submitted
10/11/2023
Date registered
25/01/2024
Date last updated
21/05/2024
Date data sharing statement initially provided
25/01/2024
Date results information initially provided
21/05/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Study to evaluate the safety and immunogenicity of an HIV-1 vaccine regimen of adjuvanted UVAX-1107 followed by adjuvanted UVAX-1107 or adjuvanted UVAX-1197 in healthy subjects aged 25-55 years.
Scientific title
Phase 1 Proof-of-Concept Study to Evaluate the Safety and Immunogenicity of a Priming Vaccination Regimen of Uvax Bio’s Glycan Trimmed HIV-1 Vaccine (UVAX-1107) with CpG 1018®/Aluminum Hydroxide Adjuvant in Healthy Adults (25-55 years), Followed by Boosting Vaccination Regimen Using UVAX-1107 or Wildtype Non-Glycan Trimmed HIV-1 Vaccine (UVAX-1197) with CpG 1018®/Aluminum Hydroxide Adjuvant
Secondary ID [1] 310821 0
UVAX-HIV-101
Universal Trial Number (UTN)
U1111-1299-3168
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acquired immune deficiency syndrome (AIDS / HIV) 331815 0
Condition category
Condition code
Infection 328560 328560 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a first in human testing of a novel HIV-1 vaccine candidate. Both UVAX-1197 and UVAX-1107 are protein nanoparticle vaccines displaying an uncleaved, prefusion-optimized (UFO) envelope (Env) glycoprotein from HIV-1 BG505 (BG505-UFO). The UVAX-1197 displays fully glycosylated UFO Env trimers with wildtype glycans (WT). UVAX-1107 is derived from UVAX-1197 by enzymatic “glycan trimming” (GT) of N-linked glycans in order to better expose major neutralizing epitopes on the surface of BG505-UFO Env to immune recognition. The optimized vaccine immunogens will be mixed with Aluminum Hydroxide (AH) and CpG 1018 adjuvants to enhance the immune response. Subject participation is expected to last up to 374 days, including up to a 30-day screening period and a 337-day study period.
Part 1 of the study will be a safety lead-in cohort in which 4 participants will receive 2 priming vaccinations of a half dose of adjuvanted UVAX-1107 (administered in 0.5ml intramuscular injection) on Days 1 and 57 followed by boosting vaccinations of a half dose of adjuvanted UVAX-1197. on days 141 and 225, administered as intra-muscular (IM) injections. Safety will be reviewed after subjects in Part 1 reach Day 8, prior to opening Part 2.
A separate group of participants will be enrolled in Part 2 of the study. Five sentinel participants (2 from each of the active treatment groups and 1 from the placebo group) will be randomized. Safety will be reviewed after these first five Part 2 sentinel participants reach Day 8, prior to opening randomization to the remaining participants in Part 2.
Participants in Part 2 will be randomized to the following treatment arms to receive either:
- Priming vaccinations of adjuvanted UVAX-1107 (full dose, administered in 0.5ml intramuscular injection) on Days 1 and 57 followed by boosting vaccinations of adjuvanted UVAX-1197 (full dose, administered in 0.5ml intramuscular injection) on Days 141 and 225.
- Priming vaccinations of adjuvanted UVAX-1107 (full dose) on Days 1 and 57 followed by boosting vaccinations of adjuvated UVAX-1107 (full dose) on Days 141 and 225.

Vaccinations will be administered by trained staff at the study site(s) according to site’s SOPs. Details regarding dosing, including the dose administered, arm, and the date and time of dosing, will be recorded in the subjects source notes and electronic case report form (eCRF).
Intervention code [1] 327234 0
Prevention
Intervention code [2] 327611 0
Treatment: Drugs
Comparator / control treatment
Saline will be used as the placebo
- Intra-muscular injection of Saline (0.5ml) on Days 1, 57, 141, and 225.
Control group
Placebo

Outcomes
Primary outcome [1] 336383 0
To assess local and systemic reactogenicity following vaccination (Day 1 to Day 8, inclusive) following each vaccination.
Timepoint [1] 336383 0
Days 1 through Day 7 after each vaccination.
Primary outcome [2] 336384 0
To determine if antibody responses are induced at 2 weeks after each vaccination using anti-HIV-1 protein IgG.
Timepoint [2] 336384 0
Pre-vaccination timepoints (Day 1, Day 57, Day 141 and Day 225) and ~2 weeks after each vaccination (Day 15, Day 71, Day 155 and Day 239) and Day 337 post enrolment/End of study (EOS).
Secondary outcome [1] 428106 0
To assess serious adverse events (SAEs) or adverse events of special interest (AESI) attributed to vaccination.
Timepoint [1] 428106 0
At all visits, Day 1, Day 8, Day 15, Day 29, Day 57, Day 64, Day 71, Day 85, Day 141, Day 148, Day 156, Day 169, Day 225, Day 232, Day 239, Day 253 and Day 337 post enrolment/End of Study (EOS).
Secondary outcome [2] 428107 0
To describe occurrence of Medically Attended Adverse Events (MAAEs).
Timepoint [2] 428107 0
On pre- and post-dose Day 1, Day 8, Day 15, Day 29, pre- and post-dose Day 57, Day 64, Day 71, Day 85, pre- and post-dose Day 141, Day 148, Day 156, Day 169, pre- and post-dose Day 225, Day 232, and Day 253
Secondary outcome [3] 428108 0
To describe occurrence of treatment emergent adverse events (TEAEs)
Timepoint [3] 428108 0
Endpoint will evaluate TEAEs reported until Day 29 following each vaccination (Day 1, Day 8, Day 15, Day 29, post-dose Day 57, Day 64, Day 71, Day 85, post-dose Day 141, Day 148, Day 156, Day 169, post-dose Day 225, Day 232, and Day 253).
Secondary outcome [4] 428109 0
To assess changes in chemistry, haematology, and bleeding indices from pre-vaccination to 7 days following each vaccination.
Timepoint [4] 428109 0
Screening visit, Day 8, pre-dose Day 57, Day 64, pre-dose Day 141, day 148, pre-dose Day 225, Day 239 and Day 337 post-enrolment/End of Study (EOS)
Secondary outcome [5] 428110 0
To assess changes in vital signs following each vaccination.
Timepoint [5] 428110 0
All study visits (Screening, pre- and post-dose Day 1, Day 8, Day 15, Day 29, pre- and post-dose Day 57, Day 64, Day 71, Day 85, pre- and post-dose Day 141, Day 148, Day 156, Day 169, pre- and post-dose Day 225, Day 232, Day 253 and Day 337.
Secondary outcome [6] 428111 0
To determine difference in autologous neutralizing antibody response across dose groups
Timepoint [6] 428111 0
Pre-vaccinations timepoints (Day 1, Day 57, Day 141 and Day 225), and ~2 weeks after each vaccination (Day 15, Day 71, Day 155, and Day 239) and at the EOS (Day 337 post-enrolment).
Secondary outcome [7] 428112 0
To determine difference in heterologous neutralizing antibody response across dose groups
Timepoint [7] 428112 0
Conditional testing at pre-vaccination timepoints (Day 1, Day 57, Day 141 and Day 225), and remaining 2-week post-vaccination timepoints (Day 15, Day 71) may be performed based on detection of heterologous neutralizing antibody results at Days 155 and 239.

Eligibility
Key inclusion criteria
1. Male or female, 25-55 years of age, inclusive, at screening.
2. Stable health status, as established by physical examination and medical history.
3. Capable of providing written informed consent.
4. Female participants of reproductive potential must be non-pregnant and non lactating, and if of child- bearing potential must agree to be heterosexually inactive from at least 21 days prior to enrolment (Day 1) and through 90 days following last study vaccination or agrees to consistently use highlyle effective method of birth control and refrain from donating oocytes from at least 21 days prior to enrolment and through 90 days following last study vaccination.
5. Male participants must:
a. Agree not to donate sperm from the time of signing consent until at least 90 days after the last dose of study drug.
b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception until at least 90 days after the last dose of study drug.
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom.
Minimum age
25 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Chronic illness being treated actively and with evidence of recent adjustments in medications for worsening or fluctuating symptoms in the past 3 months, or hospitalizations / procedural interventions in the past 6 months.
2. Body mass index (BMI) of less than 17 and greater than 32 kg/m2 at screening.
3. Vital signs grading greater than 1 at screening
4. Toxicity grading greater than 1 for screening laboratory test results.
5. Any abnormal, clinically significant ECG result at screening.
6. High risk of contracting HIV .
7. History of cancer (malignancy) in the last 10 years.
8. Use of narcotic/illicit drugs or a history of drug/alcohol abuse within the past 2 years.
9. Has donated blood or suffered from blood loss of more than 450 mL (1 unit of blood) within 60 days prior to screening, or donated plasma within 14 days prior to screening.
10. Receipt of immunoglobulin, blood-derived products, high dose systemic corticosteroids, or other immunosuppressant drugs within 90 days prior to Day 1 or who expect to receive immunoglobulin or another blood product during the study.
11. Receipt of a licensed or emergency/provisional approval vaccine within the last 30 days prior to Day 1.
12. Known hypersensitivity to any component of the study vaccines, including history of anaphylaxis or other significant allergy in the opinion of the Investigator.
13. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic) or chronic hematologic disorder (anemia, sickle cell, thalassemia).
14. Evidence of HIV, positive hepatitis B surface antigen or core antibody or hepatitis C antibodies by screening test.
15. Any chronic or degenerative neurological disease or history of significant neurological disorder.
16. Evidence of cardiovascular, pulmonary, renal, hepatobiliary disease or any other baseline condition (history and medication review) that has required active treatment or intervention.
17. Evidence of major depression disorder not well controlled in the past 2 years or history of suicidal ideation or attempt in the past 2 years.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
The final analysis will occur following the final database lock and include output from all primary and secondary endpoints. Two interim analyses are planned; one to occur after all subjects have completed Day 85 and the second after completing Day 169.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
30/01/2024
Actual
30/01/2024
Date of last participant enrolment
Anticipated
29/03/2024
Actual
28/03/2024
Date of last data collection
Anticipated
28/02/2025
Actual
Sample size
Target
34
Accrual to date
Final
34
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25753 0
Nucleus Network - Melbourne
Recruitment postcode(s) [1] 41576 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 315064 0
Commercial sector/Industry
Name [1] 315064 0
UVAX Bio LLC
Country [1] 315064 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Uvax Bio Australia, Pty, Ltd, a wholly owned subsidiary of Uvax Bio, LLC
Address
Level 5, 63 Pirie Street, Adelaide, South Australia, 5000
Country
United States of America
Secondary sponsor category [1] 317085 0
Commercial sector/Industry
Name [1] 317085 0
Avance Clinical Pty Ltd
Address [1] 317085 0
213 Glynburn Road, Firle, South Australia 5070
Country [1] 317085 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314016 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 314016 0
55 commercial road, melbourne VIC 3004
Ethics committee country [1] 314016 0
Australia
Date submitted for ethics approval [1] 314016 0
23/10/2023
Approval date [1] 314016 0
06/12/2023
Ethics approval number [1] 314016 0

Summary
Brief summary
This is a first in human testing of novel HIV-1 protein nanoparticles vaccine candidates, UVAX-1107 and UVAX-1197 mixed with Aluminum Hydroxide (AH) and CpG 1018 adjuvants. After meeting all eligibility
criteria, approximately 34 participants will receive a 4 dose vaccination regimen of either 2 priming vaccinations of UVAX-1107 followed by 2 boosting vaccinations of UVAX-1197, or 4 doses of UVAX-1107, or placebo. Subject participation is expected to last up to 374 days, including up to a 30-day screening period and a 337-day study period during which subjects will be followed for safety and immunogenicity outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130130 0
Ms Christina Chang
Address 130130 0
Nucleus Network Melbourne, 235 Ryrie Street, Geelong, 3220, Victoria
Country 130130 0
Australia
Phone 130130 0
+61 385939800
Fax 130130 0
Email 130130 0
c.chang@nucleusnetwork.com.au
Contact person for public queries
Name 130131 0
Mr Nucleus Network Melbourne
Address 130131 0
Nucleus Network Melbourne, Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 130131 0
Australia
Phone 130131 0
+61 1800 243 733
Fax 130131 0
Email 130131 0
melbourne@nucleusnetwork.com
Contact person for scientific queries
Name 130132 0
Dr Pedro Garbes, MD,
Address 130132 0
UVax Bio Australia Pty Ltd Level 5, 63 Pirie Street, Adelaide, South Australia 5000,
Country 130132 0
Australia
Phone 130132 0
+61 1 800 665 872
Fax 130132 0
Email 130132 0
ausct101@uvaxbio.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy and Intellectual property considerations


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.