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Phase 1 Study to Assess Safety, Reactogenicity and Immunogenicity of the HDT-301 Vaccine Against COVID-19

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ClinicalTrials.gov Identifier: NCT04844268
Recruitment Status : Not yet recruiting
First Posted : April 14, 2021
Last Update Posted : April 19, 2021
Sponsor:
Information provided by (Responsible Party):
SENAI CIMATEC

Brief Summary:

This is a phase I, open label, dose ranging clinical trial in healthy males and non-pregnant females, 18 to 55 years of age, inclusive, who are SARS-CoV-2 seronegative at screening. The trial is designed to assess the safety, reactogenicity and immunogenicity of HDT-301, which is a novel Lipid-Inorganic Nanoparticle (LION™) formulated replicating RNA-based vaccine that encodes for a full-length spike (S) protein of the SARS-CoV-2 virus. As a replicating mRNA vaccine, HDT-301 has the potential to allow the advantages of dose sparing, and possibly administration as a single dose, compared with other mRNA platforms.

Enrollment will occur at one domestic site. 78 subjects will receive two intramuscular (IM) injections of HDT-301 at a dose of 1 µg, 5 µg and 25 µg on either Days 1 and 29 or on Days 1 and 57. ELISA IgG responses will be the primary endpoint assessed for dose-response and, for post dose one responses, as an initial exploration of feasibility of a one-dose strategy. Scheduled interim immunogenicity evaluations will be conducted for pre-specified timepoints. Subjects will be followed for safety and immunogenicity through 12 months after the second vaccination. The primary objective is to evaluate the safety and reactogenicity of a 2-dose vaccination schedule of HDT-301, with the second dose given at a 28 or 56 day interval, across 3 dosages in healthy adults.


Condition or disease Intervention/treatment Phase
SARS-CoV-2 Biological: Cohort 1 HDT 301 vaccine Biological: Cohort 2 HDT 301 vaccine Biological: Cohort 3 HDT 301 vaccine Phase 1

Detailed Description:

In this phase 1 dose ranging study, four dose cohorts (1 µg, 5 µg and 25 µg) of 26 subjects will be sequentially enrolled, of which: 16 subjects without previous exposure to SARS-CoV-2, confirmed through the absence of anti-SARS-CoV-2 IgG; 5 subjects previously positive for SARS-CoV-2 confirmed by RT-PCR, with mandatory presence of antibodies against SARS-CoV-2; and 5 subjects with previous positive diagnosis for SARS-CoV-2 by RT- PCR, asymptomatic, and with persistent negative result for anti-SARS-CoV-2 IgG.

The study will begin with the 16 subjects without previous exposure to SARS-CoV-2 (naïve subjects). Each dose cohort subjects will be randomized with equal probability to receive the second dose, of the same dosage, at either 28 days or 56 days after the first dose. For each of the three dose groups, a sentinel group of 4 subjects will be initially enrolled and followed through Day 8 post dose one for safety. If no halting rules are met by Day 8 enrollment will proceed to the remaining 12 subjects. Following enrollment of the first cohort, the second dose cohort will be enrolled in a similar fashion, with the sentinel group enrolled after a 7-day safety observation period has elapsed following vaccination of the last subject in the first cohort. Cohort 3 will be enrolled in a similar fashion following cohort 2. The 10 subjects with previous positive RT-PCR history for SARS-CoV-2 will be enrolled in the study only after the end of doses of each cohort they are inserted in.

There is no placebo group in order to more easily perform important interim analyses and to avoid the time and expense of recruitment and enrollment of subjects, and collection of data and samples, including PBMC samples, from those not exposed to the vaccine. Inclusion of a small number of placebo subjects would likely not meaningfully improve assessment of causality of adverse events. At the screening visit, serum specimens will be obtained for testing by IgG ELISA to identify persons seropositive to SARS-CoV-2 S protein, who will be excluded from enrollment in order to perform this first assessment of safety and immunogenicity in a homogenous cohort of naïve subjects. Subjects that present IgG anti-SARS-CoV-2 in serum samples may be excluded of the study as long as they present positive history of RT-PCR for (5 subjects of each cohort) and the enrollment and investigation of these subjects in the study will only begin after the end of the immunization of the naïve subjects.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Title of Study: A Phase 1, Randomized, Open-Label, Dose-Escalation Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Nanoparticle Carrier-Formulated Self-Replicating Replicon RNA (repRNA) Vaccine in Healthy Adults
Estimated Study Start Date : May 2021
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : July 2022

Arm Intervention/treatment
Experimental: Cohort 1
Two intramuscular (IM) injections of HDT-301 at a dose of 1 µg, on either Days 1 and 29 or on Days 1 and 57
Biological: Cohort 1 HDT 301 vaccine
Two Intramuscular injections of 1 µg of novel Lipid-Inorganic Nanoparticle (LION™) formulated replicating RNA-based vaccine

Experimental: Cohort 2
Two intramuscular (IM) injections of HDT-301 at a dose of 5 µg, on either Days 1 and 29 or on Days 1 and 57
Biological: Cohort 2 HDT 301 vaccine
Two Intramuscular injections of 5 µg of novel Lipid-Inorganic Nanoparticle (LION™) formulated replicating RNA-based vaccine

Experimental: Cohort 3
Two intramuscular (IM) injections of HDT-301 at a dose of 25 µg, on either Days 1 and 29 or on Days 1 and 57
Biological: Cohort 3 HDT 301 vaccine
Two Intramuscular injections of 25 µg of novel Lipid-Inorganic Nanoparticle (LION™) formulated replicating RNA-based vaccine




Primary Outcome Measures :
  1. Safety and tolerability of two doses of HDT-1 vaccine [ Time Frame: Day 1 ]
    Levels of Spike-specific antibody responses measured by IgG binding to the Spike protein using ELISA.

  2. Safety and tolerability of two doses of HDT-1 vaccine [ Time Frame: Day 29 ]
    Levels of Spike-specific antibody responses measured by IgG binding to the Spike protein using ELISA.

  3. Safety and tolerability of two doses of HDT-1 vaccine [ Time Frame: Day 57 ]
    Levels of Spike-specific antibody responses measured by IgG binding to the Spike protein using ELISA.


Secondary Outcome Measures :
  1. Immunogenicity of two doses of HDT-1 vaccine [ Time Frame: 28 days after the second vaccination. ]
    Levels of IgG ELISA to the SARS-CoV-2 S protein

  2. Immunogenicity of two doses of HDT-1 vaccine [ Time Frame: Days 29 or 57 ]
    Levels of IgG ELISA to the SARS-CoV-2 S protein on the day of and prior to the second vaccination (Day 29 or 57).

  3. Immunogenicity of two doses of HDT-1 vaccine [ Time Frame: During 12 months of follow up ]
    Levels of antibody subclasses as measured by IgG1, IgG2, IgG3, and IgG4 ELISA to the SARS-CoV-2 S protein at all timepoints.


Other Outcome Measures:
  1. Immunogenicity of two doses of HDT-1 vaccine (IgG) [ Time Frame: During 12 months of follow up ]
    Levels of IgG ELISA to the SARS-CoV-2 S protein at other time points

  2. Immunogenicity of two doses of HDT-1 vaccine (IgM and IgA) [ Time Frame: During 12 months of follow up ]
    Levels of IgM and IgA ELISA to the SARS-CoV-2 S protein at various time points

  3. Immunogenicity of two doses of HDT-1 vaccine (B and T cells) [ Time Frame: During 12 months of follow up ]
    Levels of B cell and T cell responses to the vaccine.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Males and females between 18 years and 55 years of age.
  2. Must be in good general health as confirmed by a medical history and physical exam.
  3. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of each study vaccination, must not be breast-feeding, and are required to use one of the following methods of contraception from enrollment in study until 30 days after last injection (only if in sexual relationships with men): hormonal (e.g. oral, transdermal, intravaginal, implant, or injection); double barrier (i.e., condom, diaphragm, or cervical cap with spermicide); intrauterine device (IUD) or system (IUS); vasectomized partner (6 months minimum); or abstinence; bilateral tubal ligation (if no conception post-procedure); tubal occlusion; or bilateral salpingectomy. These precautions are necessary due to unknown effects that HDT-301 might cause in a fetus or newborn infant. Women are considered non-child-bearing potential if they are post-menopausal (defined as at least 12 months spontaneous amenorrhea and confirmed with FSH > 40 mIU/ml) or have had documented hysterectomy and/or oophorectomy.
  4. The following screening laboratory values must be within the normal ranges or not clinically significant as determined by the Investigator and approved by the Medical Monitor: sodium, potassium, BUN, ALT, AST, total bilirubin, alkaline phosphatase, creatinine, fasting glucose, total WBC count, hemoglobin, and platelet count. Abnormal results may be repeated once for confirmation at Investigator discretion.
  5. The following serology tests must be negative: SARS-CoV-2 antibody, HIV 1/2 antibody, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) antibody.
  6. Negative test for recreational drugs and alcohol per Clinical Research Unit standards.
  7. Normal or not clinically significant urinalysis as determined by the study clinician or designee. Abnormal results may be repeated at Investigator discretion.
  8. Normal blood count within 10 days before the administration of the first dose of the HDT-301 vaccine.
  9. Must be capable of completing a study memory aid in English.
  10. Must give informed consent, be able and willing to make all evaluation visits, be reachable by telephone or personal contact by the study site personnel, and have a permanent address.

    -

Exclusion Criteria:

  1. Participation in another experimental protocol and/or receipt of any investigational products within the past 3 months prior to Screening.
  2. Treatment with immunosuppressive drugs (e.g., oral or injected steroids, such as prednisone; high dose inhaled steroids) or cytotoxic therapies (e.g., chemotherapy drugs or radiation) in the past 6 months prior to Screening (except for participants who were diagnosed with COVID-19 and received corticosteroids as an anti-inflammatory for more than 3 weeks).
  3. Received a blood transfusion within past 3 months prior to Screening.
  4. Donated blood products (platelets, whole blood, plasma, etc.) within past one month prior to Screening.
  5. Received any vaccine within past 1 month prior to Screening or have any planned immunizations while on study, with the exception of seasonal influenza vaccine which can be given after 1 month post the second study injection.
  6. History of autoimmune disease or other causes of immunosuppressive states.
  7. History of any other acute or chronic illness (including cardiovascular, pulmonary, neurological, hepatic, rheumatic, hematological, metabolic or renal disorders, uncontrolled hypertension), or use of medication that, in the opinion of the Principal Investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.
  8. Rash, tattoos, or any other dermatological condition that could adversely affect the vaccine injection site or interfere with its evaluation.
  9. BMI ≥ 32.
  10. Hypertension (systolic > 150 or diastolic > 95).
  11. History of significant psychiatric illness with current use of medication.
  12. Known or suspected alcohol or drug abuse within the past 6 months prior to Screening.
  13. Chronic tobacco user (> 20 pack years).
  14. Subjects with a history of previous anaphylaxis or severe allergic reaction to vaccines or unknown allergens.
  15. Subjects who are unlikely to cooperate with the requirements of the study protocol.

    -


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04844268


Contacts
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Contact: Bruna Machado, PhD 55 (71) 3879.5624 / 5267 brunam@fieb.org.br
Contact: Carolina Macedo, PhD 55 (71) 3879.5624 / 5267 carolthemacedo@gmail.com

Sponsors and Collaborators
SENAI CIMATEC
Investigators
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Principal Investigator: Roberto Badaró, PhD Principal Investigator
Study Chair: Steven Reed, PhD Study collaborator
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Responsible Party: SENAI CIMATEC
ClinicalTrials.gov Identifier: NCT04844268    
Other Study ID Numbers: CIMATEC01
First Posted: April 14, 2021    Key Record Dates
Last Update Posted: April 19, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Vaccines
Immunologic Factors
Physiological Effects of Drugs