Safety and Immunogenicity of a Self-Amplifying RNA Vaccine Against Crimean-Congo Hemorrhagic Fever

NCT06799013 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: HDT-321-001W15QKN-16-9-1002 / 23-86397-01
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to assess the safety, tolerability and immunogenicity of three dosage levels, and a single or two-dose administration regimen, of the investigational HDT-321 product administered intra-muscularly. The main questions it aims to answer are:

• Is HDT-321 safe to use
• Does HDT-321 provide protection against Crimean-Congo hemorrhagic fever virus (CCHFV) Researchers will record any adverse events and test blood samples to see if HDT-321 is safe and works to protect participants against Crimean-Congo hemorrhagic fever virus (CCHFV) Participants will:
• Receive 1 or 2 doses of HDT-321
• Complete a memory aid and measurements for 7 days after receiving each dose of HDT-321
• Be followed throughout the study using phone calls and clinic visits to check for and record adverse events
• Provide blood samples at specific study visits

Conditions

Vaccine; Crimean-Congo Hemorrhagic Fever

Keywords

Vaccine; Healthy; 18-64; Male; Female; Preventative

Outcome Measures

Primary Outcomes (4)

• Solicited local and systemic adverse events (AEs)

  Frequency and grade of solicited local and systemic AEs during the 7-day follow-up period after each study injection (i.e. the day of administration and 6 subsequent days).

  Day 1-7 post administration

• Unsolicited study product related adverse events

  Frequency and grade of unsolicited study product related AEs reported during the 28-day follow-up period after each study injection.

  Day 1-28 post administration

• Laboratory abnormalities

  Occurrence of laboratory abnormalities at 7 days post injection visit (increased or decreased outside normal ranges, as determined by the FDA Guidance for Industry Toxicity Grading Scale for Healthy Adults Enrolled in Preventive Vaccine Clinical Trials, 2007)

  Day 1-7 post administration

• Serious AEs, AEs of Special Interest, Medically Attended AEs, and New-Onset of Chronic Diseases

  Frequency and grade of Serious AEs (SAEs), AEs of Special Interest (AESIs), Medically-Attended AEs (MAAEs), and New-Onset of Chronic Diseases (NOCDs) during the duration of participation in the study.

  Day 1 to end of study participation (Day 394)

Secondary Outcomes (1)

• Immunogenicity of HDT-321

  Day 1 to Day 57

Other Outcomes (5)

• Exploratory immunogenicity of HDT-321

  Day 1 to end of study participation (Day 394)

• Exploratory immunogenicity of HDT-321

  Day 57 to the end of study participation (Day 394)

• Exploratory Immunogenicity of HDT-321

  Day 1 to end of study participation (Day 394)

Study Arms (4)

Group 1

EXPERIMENTAL

Group 1 will include 12 participants who will receive a 10 ug two dose schedule of HDT-321 at day 1 and day 29.

Biological: 10 ug HDT 321

Group 2

EXPERIMENTAL

Group 2 will include 12 participants who will receive a 25 ug, two dose schedule of HDT-321 at day 1 and day 29.

Biological: 25ug HDT-321

Group 3

EXPERIMENTAL

Group 3 will include 12 participants who will receive a 50 ug one dose schedule of HDT-321 at day 1.

Biological: 50ug HDT-321

Group 4

EXPERIMENTAL

Group 4 will include 12 participants who will receive a 50 ug two dose schedule of HDT-321 at day 1 and day 29.

Biological: 50ug HDT-321

Interventions

10 ug HDT 321 BIOLOGICAL

HDT-321 Investigational Vaccine (a Nanoparticle Carrier-Formulated self-amplifying RNA encoding the NP of CCHFV)

Group 1

25ug HDT-321 BIOLOGICAL

HDT-321 Investigational Vaccine (a Nanoparticle Carrier-Formulated self-amplifying RNA encoding the NP of CCHFV)

Group 2

50ug HDT-321 BIOLOGICAL

HDT-321 Investigational Vaccine (a Nanoparticle Carrier-Formulated self-amplifying RNA encoding the NP of CCHFV)

Group 3; Group 4

Eligibility Criteria

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

You may qualify if:

• Males and non-pregnant females 18 to 64 years of age at the time of signing the ICF.
• Body mass index (BMI) 17 to 35 inclusive at screening.
• Considered by the PI or designee to be in good general health as determined by medical history, physical examination, vital sign measurements\*, and clinical laboratory assessments conducted no more than 30 days prior to the first study injection administration.
• Screening laboratory values within the laboratory reference ranges or considered non-clinically significant (NCS) if within Grade 1 severity on the toxicity grading scale.
• Negative human immunodeficiency virus (HIV) 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody.
• Women of childbearing potential must agree to use or have practiced true abstinence or use at least one acceptable primary form of contraception3 for at least 30 days prior to the first injection and for 60 days after the last injection. Female participants 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 injection.
• Able to understand and comply with planned study procedures and willing to be available for all study required procedures, visits, and telephone calls for the duration of the study.
• Provide written informed consent before initiation of any study procedures.
• Willing to abstain from donating whole blood or blood derivatives 30 days prior to screening and for the duration of the study.
• Willing to refrain from receiving any licensed vaccine within 28 days prior to and after scheduled study injections.

You may not qualify if:

• Any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes study participation. Including Acute, subacute, intermittent, or chronic medical diseases or conditions that would place the subject at an unacceptable risk of injury, render the subject unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the subject's successful completion of the trial. Significant respiratory disease (COPD) requiring daily medications, asthma that is not well controlled, significant cardiovascular disease, history of myocarditis or pericarditis, myocardial infarction, coronary artery bypass surgery or stent placement, or uncontrolled cardiac arrhythmia, Neurological or neurodevelopmental conditions, ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell and squamous cell carcinoma of the skin, blood dyscrasias or significant disorder of coagulation, chronic liver disease, including fatty liver, autoimmune disease, including localized or history of psoriasis or hypothyroidism without a defined non-autoimmune cause and Immunodeficiency of any cause.
• Abnormal screening electrocardiogram (ECG)
• History of hypersensitivity or severe reactions to previous vaccinations
• History of hypersensitivity or severe reactions to products known to contain polyethylene glycol (PEG).
• Allergy to antibiotics structurally similar to kanamycin (including but not limited to neomycin, streptomycin, tobramycin, and gentamycin).
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immunemodifying drugs within 6 months prior to the first study injection (for corticosteroids: prednisone ≥20 mg/day or equivalent). Intra-articular, inhaled, nasal, and topical steroids are allowed.
• Received immunoglobulins or any blood products within 60 days prior to enrollment/Day 1.
• Donated blood products within 30 days prior to enrollment/Day 1.
• Received an investigational or non-registered medicinal product within 30 days prior to screening.
• Currently enrolled, or plan to participate, in another clinical trial with an investigational agent to be received during the study period.
• Received or plans to receive any non-study vaccine within 28 days before and after each study injection.
• Febrile illness\*, as determined by the participating site PI or appropriate sub-investigator, with or without fever (oral temperature ≥38.0°C/100.4°F), within 24 hours prior to each study injection.
• Current heavy smoking/vaping (defined as 1 pack or more of cigarettes a day or vaping equivalent\*). \*1-2 mL of 20 mg/mL of nicotine salt
• Known or suspected alcohol or illicit drug abuse within the past 12 months prior to Study Day 1.
• Breastfeeding or plans to breastfeed from the time of the first vaccination through 60 days after the last study injection.

Sponsors & Collaborators

• HDT Bio: lead
• DFNet Research Inc.: collaborator
• Technical Resources International, Inc. (TRI): collaborator
• BioAgilytix Labs, LLC: collaborator
• The University of Texas Medical Branch, Galveston: collaborator
• Clinical Trials of Texas, Inc.: collaborator
• Quest Laboratories: collaborator

Study Sites (1)

Flourish Research San Antonio (Clinical Trials of Texas)

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Hemorrhagic Fever, Crimean

Condition Hierarchy (Ancestors)

Arbovirus Infections; Vector Borne Diseases; Infections; Tick-Borne Diseases; Virus Diseases; Bunyaviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Study Officials

• Malcolm Duthie, PhD

  HDT Bio

  STUDY DIRECTOR

Central Study Contacts

James Keary

CONTACT

206-567-8230; james.keary@hdt.bio

Aude Frevol

CONTACT

206-704-5705; aude.frevol@hdt.bio

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Four groups of 12 participants across three dose levels will be sequentially recruited in the study, starting with the lowest dose. The three dose levels and four treatment groups are outlined below. Group 1: 12 participants receive 10 μg vaccinations on Day 1 and Day 29 Group 2: 12 participants receive 25 μg vaccinations on Day 1 and Day 29 Group 3: 12 participants receive 50 μg vaccination on Day 1 Group 4: 12 participants receive 50 μg vaccinations on Day 1 and Day 29

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: January 29, 2025
• Study Start: July 10, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)