A Phase 1 Safety Study of Dengusiil in Healthy Adults

• ClinicalTrials.gov Identifier: NCT04035278
• Recruitment Status: Completed
• First Posted: July 29, 2019
• Last Update Posted: January 3, 2024
• Sponsor: Serum Institute of India Pvt. Ltd.
• Collaborator: PPD Australia Pty Ltd
• Information provided by (Responsible Party): Serum Institute of India Pvt. Ltd.

Study Description

Brief Summary:

This is a Phase 1 study to assess safety and tolerability of a single subcutaneous dose of Dengusiil in healthy adults of 18 to 45 years of age. In this study, immune response to Dengusiil will also be assessed over a period of 6 months and vaccine viremia will also be assessed over a period of 12 days after administration of vaccine.

Condition or disease	Intervention/treatment	Phase
Prevention of Dengue Fever	Biological: Dengusiil; Biological: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 1, Double Blind, Randomized, Placebo-controlled Study to Evaluate the Safety and Immunogenicity of Dengusiil in Healthy Adults
• Actual Study Start Date: December 17, 2019
• Actual Primary Completion Date: June 11, 2021
• Actual Study Completion Date: June 11, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dengusiil	Biological: Dengusiil; Dengusiil is provided as lyophilized powder to be reconstituted with 0.5 mL sterile water for injection (sWFI).The reconstituted vaccine is injected as a single 0.5 mL subcutaneous (SC) dose.; Other Name: Live attenuated tetravalent vaccine containing all four dengue virus serotypes (DENV1, 2, 3 and 4)
Placebo Comparator: Placebo	Biological: Placebo; Placebo is supplied as a vial of lyophilized powder containing all the components of the vaccine except dengue virus serotypes (DENV1, 2, 3 and 4) to be reconstituted with 0.5 mL sterile water for injection (sWFI).The reconstituted product is injected as a single 0.5 mL subcutaneous (SC) dose.; Other Name: Lyophilized powder containing all the components of the vaccine except DENV serotypes 1, 2, 3 and 4

Outcome Measures

Primary Outcome Measures :

1. Solicited local and systemic reactions [ Time Frame: 21 days ]
2. Occurrence, severity, and relatedness to vaccination of unsolicited adverse events [ Time Frame: 21 days ]
3. Occurrence, severity, and relatedness to vaccination of serious adverse events [ Time Frame: 180 days ]
4. Proportion of participants with clinically significant abnormal safety laboratory (hematology and chemistry parameters) findings [ Time Frame: 8 days ]
5. Proportion of participants with clinically significant physical examination and vital signs findings [ Time Frame: 180 days ]

Secondary Outcome Measures :

1. Proportion of participants with seroconversion for DENV-1 to 4 virus neutralization antibodies (PRNT50) titer [ Time Frame: 84 days ]
2. The percentage of participants seropositive for DENV-1 to 4 virus neutralizing antibodies [ Time Frame: 84 days ]
3. The percentage of participants seropositive for DENV-1 to 4 virus neutralizing antibodies [ Time Frame: 180 days ]
4. Geometric mean titers (GMTs) of DENV-1 to 4 virus neutralization antibodies [ Time Frame: 56 days ]
5. GMTs of DENV-1 to 4 virus neutralization antibodies [ Time Frame: 84 days ]
6. Proportion of participants with viremia for each of DENV-1 to 4 [ Time Frame: 12 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Healthy adults aged 18-45, men, or women.
2. Seronegative for Dengue NS1 and IgM at screening indicating no current dengue infection
3. Seronegative for dengue IgG at screening
4. Participants who are willing to comply with the requirements of the study protocol and attend scheduled visits.
5. Participants who give written informed consent approved by the Human Research Ethics Committee (HREC) governing the site.
6. Participants must have the laboratory parameters within normal range.
7. Participants with Body Mass Index (BMI) between 18 to 30 (both inclusive)
8. Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations those are acceptable for study entry.

9. Participants should agree to not:

   1. donate blood for the purpose of blood transfusion
   2. donate an organ for the purpose of transplantation
   3. to share needles with other people
   4. allow their blood to come in contact with another person's mucous membranes for 84 days post-vaccination.

Exclusion Criteria:

1. Previous dengue vaccination.
2. Presence of acute infection in the preceding 14 days or presence of a temperature ≥ 38.0°C, or acute symptoms of infection greater than of "mild" severity on the scheduled date of first dosing
3. Evidence of any other significant active haematological disease, or having donated > 450 mL of blood within the past three months.
4. Evidence or history of substance abuse including alcohol or previous substance abuse within the last year.
5. Participation or planned participation in a study involving the administration of an investigational compound within the past one month or during this study period.
6. Planned administration of any vaccine not foreseen by the study protocol 4 weeks before and after dosing.
7. History of allergic disease, allergic reactions or known hypersensitivity to any component of the study vaccines.
8. Confirmed or suspected immunosuppressive or immune-deficient condition.
9. A family history of congenital or hereditary immunodeficiency.
10. Chronic administration (defined as more than 14 days) of immune-suppressants or other immune-modifying agents within six months prior to administration of study vaccine. (For corticosteroids, this means prednisone, or equivalent, ≥ 0.5 mg/kg/day; topical or inhalable steroids are allowed.)
11. Laboratory confirmed infection with either hepatitis B virus (HBs Ag positive), hepatitis C virus (anti-HCV positive), or human immunodeficiency virus (HIV) at screening.
12. Known bleeding disorders.
13. Administration of immunoglobulins and/or any blood products within the three months preceding the administration of study vaccines or planned administration during the study period.
14. Women who are pregnant, breast-feeding, or considering becoming pregnant.
15. Any other condition, which in the opinion of the investigator, might interfere with the study objectives, jeopardize the safety or rights of the participant or making it unlikely the participant could complete the protocol.

Contacts and Locations

Locations

Australia, South Australia

CMAX Clinical Research Pty Ltd

Adelaide, South Australia, Australia, 5000

Sponsors and Collaborators

Serum Institute of India Pvt. Ltd.

PPD Australia Pty Ltd

Investigators

• Study Director: PRASAD KULKARNI, MD; SERUM INSTITUTE OF INDIA

More Information

Publications of Results:

Gunale B, Farinola N, Yeolekar L, Shrivastava S, Girgis H, Poonawalla CS, Dhere RM, Arankalle V, Chandra Mishra A, Mehla R, Kulkarni PS. A Phase 1, double-blind, randomized, placebo-controlled study to evaluate the safety and immunogenicity of a tetravalent live attenuated dengue vaccine in adults. Vaccine. 2023 Aug 31;41(38):5614-5621. doi: 10.1016/j.vaccine.2023.07.045. Epub 2023 Jul 31.

• Responsible Party: Serum Institute of India Pvt. Ltd.
• ClinicalTrials.gov Identifier: NCT04035278
• Other Study ID Numbers: Dengusiil-01
• First Posted: July 29, 2019
• Last Update Posted: January 3, 2024
• Last Verified: December 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Dengue; Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Vaccines; Immunologic Factors; Physiological Effects of Drugs