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

Primary Purpose

Hypercholesterolemia

Status
Active
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
VXX-401
Placebo
Sponsored by
Vaxxinity, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercholesterolemia

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.

Sites / Locations

  • Northern Beaches Clinical Research
  • Sutherland Shire Clinical Research
  • Emeritus Research
  • University of the Sunshine Coast (USC)
  • Emeritus Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Placebo Comparator

Experimental

Experimental

Arm Label

VXX-401 Cohort A

VXX-401 Cohort B

VXX-401 Cohort C

VXX-401 Cohort D

Placebo Cohort A and C

Placebo Cohort B and D

VXX-401 Cohort E

VXX-401 Cohort F

Arm Description

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

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

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

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

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

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

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.

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.

Outcomes

Primary Outcome Measures

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.
Immunogenicity
Immunogenicity will be measured by serum anti-PCSK9 antibody titers
Immunogenicity
Seroconversion two-fold and four-fold from baseline
Determine optimal VXX-401 dose regimen
Measured by serum anti-PCSK9 antibody titers

Secondary Outcome Measures

Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction
Percent change from baseline in serum LDL-C concentration

Full Information

First Posted
February 20, 2023
Last Updated
October 9, 2023
Sponsor
Vaxxinity, Inc.
Collaborators
Novotech (Australia) Pty Limited
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1. Study Identification

Unique Protocol Identification Number
NCT05762276
Brief Title
A Study to Investigate the Safety, Tolerability, Immunogenicity, and Pharmacodynamics of VXX-401 Administered IM in Adult Participants
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 7, 2023 (Actual)
Primary Completion Date
June 27, 2024 (Anticipated)
Study Completion Date
June 27, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vaxxinity, Inc.
Collaborators
Novotech (Australia) Pty Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Cohorts A-D are blinded / Cohort E & F are open label
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
VXX-401 Cohort A
Arm Type
Experimental
Arm Description
VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12
Arm Title
VXX-401 Cohort B
Arm Type
Experimental
Arm Description
VXX-401 100mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12
Arm Title
VXX-401 Cohort C
Arm Type
Experimental
Arm Description
VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12
Arm Title
VXX-401 Cohort D
Arm Type
Experimental
Arm Description
VXX-401 300mcg administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12
Arm Title
Placebo Cohort A and C
Arm Type
Placebo Comparator
Arm Description
Placebo administered by intramuscular (IM) injection at Week 0, Week 4, and Week 12
Arm Title
Placebo Cohort B and D
Arm Type
Placebo Comparator
Arm Description
Placebo administered by intramuscular (IM) injection at Week 0, Week 4, Week 8 and Week 12
Arm Title
VXX-401 Cohort E
Arm Type
Experimental
Arm Description
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.
Arm Title
VXX-401 Cohort F
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
VXX-401
Intervention Description
A synthetic PCSK9 peptide-based immunotherapy
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
Normal saline
Primary Outcome Measure Information:
Title
Frequency of adverse events
Description
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.
Time Frame
30 weeks
Title
Immunogenicity
Description
Immunogenicity will be measured by serum anti-PCSK9 antibody titers
Time Frame
Baseline to Week 16, 20, 24, and 30
Title
Immunogenicity
Description
Seroconversion two-fold and four-fold from baseline
Time Frame
Baseline to Week 16, 20, 24, and 30
Title
Determine optimal VXX-401 dose regimen
Description
Measured by serum anti-PCSK9 antibody titers
Time Frame
Baseline to Week 16, 20, 24, and 30
Secondary Outcome Measure Information:
Title
Evaluation of low-density lipoprotein-cholesterol (LDL-C) reduction
Description
Percent change from baseline in serum LDL-C concentration
Time Frame
Baseline to Week 16, 20, 24, and 30

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sasha Rumyantsev
Organizational Affiliation
Vaxxinity, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Northern Beaches Clinical Research
City
Brookvale
State/Province
New South Wales
Country
Australia
Facility Name
Sutherland Shire Clinical Research
City
Miranda
State/Province
New South Wales
Country
Australia
Facility Name
Emeritus Research
City
Sydney
State/Province
New South Wales
Country
Australia
Facility Name
University of the Sunshine Coast (USC)
City
Morayfield
State/Province
Queensland
Country
Australia
Facility Name
Emeritus Research
City
Melbourne
State/Province
Victoria
Country
Australia

12. IPD Sharing Statement

Plan to Share IPD
No

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

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