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

NCT05762276 | Unknown Phase 1

• 1 other identifier: VXX-401-101
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 5

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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (4)

• Frequency of adverse events

  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.

  30 weeks

• Immunogenicity

  Immunogenicity will be measured by serum anti-PCSK9 antibody titers

  Baseline to Week 16, 20, 24, and 30

• Immunogenicity

  Seroconversion two-fold and four-fold from baseline

  Baseline to Week 16, 20, 24, and 30

• Determine optimal VXX-401 dose regimen

  Measured by serum anti-PCSK9 antibody titers

  Baseline to Week 16, 20, 24, and 30

Secondary Outcomes (1)

• Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction

  Baseline to Week 16, 20, 24, and 30

Study Arms (8)

VXX-401 Cohort A

EXPERIMENTAL

VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12

Drug: VXX-401

VXX-401 Cohort B

EXPERIMENTAL

VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12

Drug: VXX-401

VXX-401 Cohort C

EXPERIMENTAL

VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12

Drug: VXX-401

VXX-401 Cohort D

EXPERIMENTAL

VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12

Drug: VXX-401

Placebo Cohort A and C

PLACEBO COMPARATOR

Placebo administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12

Biological: Placebo

Placebo Cohort B and D

PLACEBO COMPARATOR

Placebo administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12

Biological: Placebo

VXX-401 Cohort E

EXPERIMENTAL

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

VXX-401 Cohort F

EXPERIMENTAL

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

Interventions

VXX-401 DRUG

A synthetic PCSK9 peptide-based immunotherapy

VXX-401 Cohort A; VXX-401 Cohort B; VXX-401 Cohort C; VXX-401 Cohort D; VXX-401 Cohort E; VXX-401 Cohort F

Placebo BIOLOGICAL

Normal saline

Placebo Cohort A and C; Placebo Cohort B and D

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants aged 18 to 75 years old, inclusive, at time of informed consent.
• LDL-C level = 2.59 mmol/L - 4.89mmol/L
• Body mass index between 18 and 35 kg/m2, inclusive at Screening, and with a minimum weight of 50 kg.
• 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.
• 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.

You may not qualify if:

• Subjects considered high risk or very high risk for ASCVD and requiring immediate treatment with LLT according to the clinical judgement of the investigator.
• 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.
• 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.
• 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.
• Triglycerides \> 5.65 mmol/L
• 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.

Sponsors & Collaborators

• Vaxxinity, Inc.: lead
• Novotech (Australia) Pty Limited: collaborator

Study Sites (5)

Northern Beaches Clinical Research

Brookvale, New South Wales, Australia

Location

Sutherland Shire Clinical Research

Miranda, New South Wales, Australia

Location

Emeritus Research

Sydney, New South Wales, Australia

Location

University of the Sunshine Coast (USC)

Morayfield, Queensland, Australia

Location

Emeritus Research

Melbourne, Victoria, Australia

Location

MeSH Terms

Conditions

Hypercholesterolemia

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Sasha Rumyantsev

  Vaxxinity, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Cohorts A-D are blinded / Cohort E \& F are open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2023
• First Posted: March 9, 2023
• Study Start: March 7, 2023
• Primary Completion: June 27, 2024
• Study Completion: June 27, 2024
• Last Updated: October 12, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5)