Safety and Immunogenicity of HDT-301 Targeting a SARS-CoV-2 Variant Spike Protein

NCT05132907 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HDT-301-002
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is Phase 1 study is to assess tolerability and immunogenicity of three dose levels of the investigational HDT-301 vaccine administered intramuscularly (IM), both in immunization-naïve participants and as a booster for those participants who previously received a SARS-CoV-2 vaccine. Safety and tolerability will be the primary endpoint assessed by incidence of adverse events at each dose through 12 months after completion of the vaccination regimen (either one dose, or two doses provided 56 days apart). Immunogenicity evaluations will be conducted for pre-specified timepoints as secondary and exploratory endpoints.

Conditions

SARS-CoV2 Infection

Outcome Measures

Primary Outcomes (4)

• Solicited AE

  Frequency and grade of solicited local and systemic AEs during a 14 day follow-up period after each vaccination (i.e., the day of vaccination and 14 subsequent days).

  Day 1-71

• Unsolicited AE

  Frequency and grade of any unsolicited AE within a 28 day period following each vaccination (i.e., the day of vaccination and 28 subsequent days).

  Day 1-85

• Lab abnormalities

  Occurrence of any laboratory abnormality (increased or decreased outside normal ranges, as determined by toxicity scales) at 7 and 28 days after each vaccination.

  Day 1-85

• Medically-attended AE, AESI and SAE

  Occurrence of medically-attended AEs and NOCMCs during the entire study period. Occurrence of AESIs during the entire study period. Occurrence of SAEs during the entire study period.

  Day 1-422

Secondary Outcomes (4)

• Immunogenicity Endpoints (magnitude of IgG response)

  Day 1-85

• Immunogenicity Endpoints (proportion of IgG responders)

  Day 1-85

• Immunogenicity Endpoints (magnitude of neutralizing antibodies)

  Day 1-85

• Immunogenicity Endpoints (proportion responding with neutralizing antibodies)

  Day 1-85

Other Outcomes (6)

• Exploratory Immunology (IgG isotype profile and magnitude)

  Day 1-422

• Exploratory Immunology (proportion with IgG isotype profile)

  Day 1-422

• Exploratory Immunology (magnitude alternate antibodies)

  Day 1-422

Study Arms (3)

Cohort 1 (previously vaccinated, two dose recipients)

EXPERIMENTAL

Cohort 1 will include individuals with vaccination against COVID-19 who will receive a two-dose schedule of HDT-301 56 days apart. Dose will be escalated from low to mid to high according to predefined safety parameters.

Biological: HDT-301

Cohort 2 (previously vaccinated, single dose recipients)

EXPERIMENTAL

Cohort 2 will include individuals with vaccination against COVID-19 who will receive a one-dose schedule of HDT-301. Dose will be escalated from low to mid to high according to predefined safety parameters.

Biological: HDT-301

Cohort 3 (previously unvaccinated)

EXPERIMENTAL

Cohort 3 will include 21 individuals with no history of vaccination against COVID-19 who will receive a two-dose schedule of HDT-301 56 days apart. Dose will be escalated from low to mid to high according to predefined safety parameters.

Biological: HDT-301

Interventions

HDT-301 BIOLOGICAL

HDT-301 Investigational Vaccine (a Nanoparticle Carrier-Formulated Replicon RNA (repRNA-CoV2S))

Cohort 1 (previously vaccinated, two dose recipients); Cohort 2 (previously vaccinated, single dose recipients); Cohort 3 (previously unvaccinated)

Eligibility Criteria

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

You may qualify if:

• Each subject must meet ALL of the following criteria in order to participate in this study:
• Male or non-pregnant female 18 through 65 years of age at the time of first vaccination.
• Known clinical and immunization status versus SARS-CoV-2.
• For Cohort 3 participants this will be either no history of COVID-19 nor reported history of vaccination against COVID-19 by Emergency Use Authorization (EUA) vaccine or investigational product.
• For Cohort 1 and Cohort 2 participants, this will be verified receipt of investigational or Emergency Use Authorization (EUA) vaccines against SARS-CoV-2 (by provision of either access to medical records, Washington state online vaccine registry, documentation of receipt of investigational vaccine, or Vaccine Card), with most recent vaccination 90 days or more prior to trial initiation (days of immunization will be noted, along with vaccine manufacturer).
• Understands and agrees to comply with the study procedures and provides written informed consent.
• In the opinion of the PI or designee, could and would comply with the requirements of the protocol (e.g., completion of Memory Aids, return for follow-up visits, availability for safety calls).
• Body mass index ≥18.0 and ≤35.0 kg/m2.
• Considered by the PI or designee to be in good general health as determined by medical history, clinical laboratory assessments, vital sign measurements, and physical examination findings at Screening.
• Women of childbearing potential1 must agree to use or have practiced true abstinence or use at least one acceptable primary form of contraception. These criteria are applicable to females in a heterosexual relationship and of childbearing potential (i.e., the criteria do not apply to subjects in a same sex relationship).
• Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of and prior to each study vaccination.
• Must agree to refrain from donating blood or plasma during the study (outside of this study).

You may not qualify if:

• Female subject who is breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last vaccination.
• Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes study participation.
• Presence of self-reported or medically documented significant medical or psychiatric condition(s).
• History of hypersensitivity or severe reactions to previous vaccinations (e.g., anaphylaxis, urticaria, other significant reaction requiring medical intervention).
• History of hypersensitivity or severe reactions to products known to contain polyethylene glycol (PEG).
• Subjects with a positive test result at Screening for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus types 1 or 2 antibodies.
• Known or suspected alcohol or drug abuse within the past 6 months prior to Screening.
• Previous participation in other studies involving study intervention containing lipid nanoparticles.
• Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose (for corticosteroids: prednisone ≥ 20 mg/day or equivalent). Inhaled, nasal and topical steroids are allowed.
• Received immunoglobulins or any blood products within 3 months prior to any study vaccination.
• Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
• Has any blood dyscrasias or significant disorder of coagulation.
• Has any chronic liver disease, including fatty liver.
• Received or plans to receive a licensed, live vaccine within 4 weeks before or after each vaccination.

Sponsors & Collaborators

• HDT Bio: lead
• Rainier Clinical Research Center: collaborator
• C3 Research Associates: collaborator

Study Sites (1)

Rainier Clinical Research

Renton, Washington, 98057, United States

Location

MeSH Terms

Conditions

COVID-19

Interventions

repRNA-CoV2S vaccine

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Steven G Reed, Ph.D

  HDT Bio

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2021
• First Posted: November 24, 2021
• Study Start: January 24, 2022
• Primary Completion: November 21, 2023
• Study Completion: May 30, 2024
• Last Updated: October 23, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)