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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05762276
• Other study ID #: VXX-401-101
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: March 7, 2023
• Est. completion date: June 27, 2024

Study information

• Verified date: October 2023
• Source: Vaxxinity, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 64
• Est. completion date: June 27, 2024
• Est. primary completion date: June 27, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• VXX-401
A synthetic PCSK9 peptide-based immunotherapy

Biological:
• Placebo
Normal saline

Locations

Country	Name	City	State
Australia	Northern Beaches Clinical Research	Brookvale	New South Wales
Australia	Emeritus Research	Melbourne	Victoria
Australia	Sutherland Shire Clinical Research	Miranda	New South Wales
Australia	University of the Sunshine Coast (USC)	Morayfield	Queensland
Australia	Emeritus Research	Sydney	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
Vaxxinity, Inc.	Novotech (Australia) Pty Limited

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Immunogenicity	Immunogenicity will be measured by serum anti-PCSK9 antibody titers	Baseline to Week 16, 20, 24, and 30
Primary	Immunogenicity	Seroconversion two-fold and four-fold from baseline	Baseline to Week 16, 20, 24, and 30
Primary	Determine optimal VXX-401 dose regimen	Measured by serum anti-PCSK9 antibody titers	Baseline to Week 16, 20, 24, and 30
Secondary	Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction	Percent change from baseline in serum LDL-C concentration	Baseline to Week 16, 20, 24, and 30