A Study to Investigate the Safety, Tolerability, Immunogenicity, and Pharmacodynamics of VXX-401 Administered IM in Adult Participants

• ClinicalTrials.gov Identifier: NCT05762276
• Recruitment Status: Active, not recruiting
• First Posted: March 9, 2023
• Last Update Posted: October 12, 2023
• Sponsor: Vaxxinity, Inc.
• Collaborator: Novotech (Australia) Pty Limited
• Information provided by (Responsible Party): Vaxxinity, Inc.

Study Description

Brief Summary:

This first-in-human (FIH) study of VXX-401, an anti-PCSK9 peptide-based immunotherapeutic candidate, is designed to assess the safety, tolerability, immunogenicity, and pharmacodynamics (PD) of VXX-401 and to determine an optimal dose regimen for LDL-C lowering in subsequent clinical trials.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: VXX-401; Biological: Placebo	Phase 1

Detailed Description:

This is multisite, multidose regimen, phase 1, first-in-human study of VXX-401, a synthetic peptide-based active immunotherapy candidate for preventing and treating hypercholesterolemia. The study will include Screening, Treatment, and Follow-up Periods. This study will enroll participants who are naïve to statin use. Each cohort from A to D is planned to randomize approximately 12 participants to receive doses of VXX-401 or placebo in a 3:1 ratio. Cohorts E and F will dose approximately 8 participants in each cohort to receive doses of VXX-401. No participants will be administered placebo in Cohorts E and F. It is planned to test up to 6 dose regimens of VXX-401, administered by IM injection into the deltoid muscle (and additionally in the thigh for the first dose in Cohorts E-F.). All eligible participants will receive a priming regimen at Week 0 (Baseline, Day 1), Week 4, and Week 12, in Cohorts A, C, E and F, and additionally at Week 8 in Cohorts B and D. The last dose administration will be at Week 12.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Cohorts A-D are blinded / Cohort E & F are open label
• Primary Purpose: Treatment
• Official Title: A Phase 1, First-in-Human, Dose Escalation Study to Evaluate the Safety, Tolerability, Immunogenicity, and Pharmacodynamics of VXX-401 in Healthy Adults
• Actual Study Start Date: March 7, 2023
• Estimated Primary Completion Date: June 27, 2024
• Estimated Study Completion Date: June 27, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: VXX-401 Cohort A; VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12	Drug: VXX-401; A synthetic PCSK9 peptide-based immunotherapy
Experimental: VXX-401 Cohort B; VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12	Drug: VXX-401; A synthetic PCSK9 peptide-based immunotherapy
Experimental: VXX-401 Cohort C; VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12	Drug: VXX-401; A synthetic PCSK9 peptide-based immunotherapy
Experimental: VXX-401 Cohort D; VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12	Drug: VXX-401; A synthetic PCSK9 peptide-based immunotherapy
Placebo Comparator: Placebo Cohort A and C; Placebo administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12	Biological: Placebo; Normal saline
Placebo Comparator: Placebo Cohort B and D; Placebo administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12	Biological: Placebo; Normal saline
Experimental: VXX-401 Cohort E; VXX-401 900mcg administered by intramuscular (IM) injection at Week 0. VXX-401 100 mcg administered by intramuscular (IM) injection at Week 4 and Week 12.	Drug: VXX-401; A synthetic PCSK9 peptide-based immunotherapy
Experimental: VXX-401 Cohort F; VXX-401 900mcg administered by intramuscular (IM) injection at Week 0. VXX-401 300 mcg administered by intramuscular (IM) injection at Week 4 and Week 12.	Drug: VXX-401; A synthetic PCSK9 peptide-based immunotherapy

Outcome Measures

Primary Outcome Measures :

1. Frequency of adverse events [ Time Frame: 30 weeks ]
   Safety and tolerability: rates of adverse events (AEs), medically attended adverse events (MAAEs), local (injection site) and systemic (generalized) reactions (i.e., reactogenicity), clinical laboratory assessments (e.g., chemistry, hematology, urinalysis, lipid profile), serum cytokine release, vital signs, physical examinations, and electrocardiograms (ECGs) through the end of the study.
2. Immunogenicity [ Time Frame: Baseline to Week 16, 20, 24, and 30 ]
   Immunogenicity will be measured by serum anti-PCSK9 antibody titers
3. Immunogenicity [ Time Frame: Baseline to Week 16, 20, 24, and 30 ]
   Seroconversion two-fold and four-fold from baseline
4. Determine optimal VXX-401 dose regimen [ Time Frame: Baseline to Week 16, 20, 24, and 30 ]
   Measured by serum anti-PCSK9 antibody titers

Secondary Outcome Measures :

1. Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction [ Time Frame: Baseline to Week 16, 20, 24, and 30 ]
   Percent change from baseline in serum LDL-C concentration

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male or female participants aged 18 to 75 years old, inclusive, at time of informed consent.
2. LDL-C level = 2.59 mmol/L - 4.89mmol/L
3. Body mass index between 18 and 35 kg/m2, inclusive at Screening, and with a minimum weight of 50 kg.
4. Male participants and their partners of childbearing potential must commit to the use of highly effective contraceptives for the study duration and for at least 12 weeks after the last dose. Men must refrain from donating sperm during this same period.
5. Female participants must be of nonchildbearing potential, or, for women of childbearing potential, must be willing to practice at least one form of highly effective contraception throughout the duration of the study and for at least 24 weeks following the last dose. Female participants must refrain from donating reproductive tissue during this same period.

Exclusion Criteria:

1. Subjects considered high risk or very high risk for ASCVD and requiring immediate treatment with LLT according to the clinical judgement of the investigator.
2. History of confirmed anergy (i.e., not able to mount an immunological response) or history of immunization failure in the 5 years prior to the Screening Visit.
3. Presence of fever >38°C or other signs or symptoms of acute disease within 1 week before the Screening and/or Visit 1; Screening and/or Visit 1 may be rescheduled at the discretion of the Investigator but must occur within the 4-week window.
4. Known disturbance of coagulation or medication (see prohibited medications criterion below); bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venipuncture.
5. Triglycerides > 5.65 mmol/L
6. Has a history of clinically significant medical disorder or psychiatric conditions, which in the opinion of the investigator may compromise the participant's safety and ability to comply with study procedures or abide by study restrictions.

Contacts and Locations

Locations

Australia, New South Wales

Northern Beaches Clinical Research

Brookvale, New South Wales, Australia

Sutherland Shire Clinical Research

Miranda, New South Wales, Australia

Emeritus Research

Sydney, New South Wales, Australia

Australia, Queensland

University of the Sunshine Coast (USC)

Morayfield, Queensland, Australia

Australia, Victoria

Emeritus Research

Melbourne, Victoria, Australia

Sponsors and Collaborators

Vaxxinity, Inc.

Novotech (Australia) Pty Limited

Investigators

• Study Director: Sasha Rumyantsev; Vaxxinity, Inc.

More Information

• Responsible Party: Vaxxinity, Inc.
• ClinicalTrials.gov Identifier: NCT05762276
• Other Study ID Numbers: VXX-401-101
• First Posted: March 9, 2023
• Last Update Posted: October 12, 2023
• Last Verified: October 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases