Safety and Immunogenicity of an Intranasal SARS-CoV-2 Vaccine (BBV154) for COVID-19

• ClinicalTrials.gov Identifier: NCT04751682
• Recruitment Status: Completed
• Last Update Posted: August 18, 2022
• Sponsor: Bharat Biotech International Limited
• Information provided by (Responsible Party): Bharat Biotech International Limited

Tracking Information

• First Submitted Date: February 8, 2021
• First Posted Date: February 12, 2021
• Last Update Posted Date: August 18, 2022
• Actual Study Start Date: March 1, 2021
• Actual Primary Completion Date: June 25, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 11, 2021)

• Incidence of immediate adverse events. [ Time Frame: within 2 hours post each vaccination ]
• The incidence of solicited local and systemic adverse events [ Time Frame: within 7 days post each vaccination ]
• The incidence of serious adverse events (SAEs) [ Time Frame: Through study completion, an average of 6 months ]
• The incidence of unsolicited adverse events [ Time Frame: Through study completion, an average of 6 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 11, 2021)

• To evaluate the humoral immune responses of BBV154 [ Time Frame: Through study completion, an average of 6 months ]
  GMT and four-fold seroconversion rate (SCR) of neutralizing antibodies (NAb's) by MNT/PRNT assays across the three groups.
• To compare the humoral responses between single dose group and double dose group. [ Time Frame: Through study completion, an average of 6 months ]
  GMT and four-fold seroconversion rate (SCR) of neutralizing antibodies (NAb's) by MNT/PRNT assays across the three groups.
• To evaluate the immune responses against spike protein of SARS-CoV-2 virus and Adenovirus vector [ Time Frame: Through study completion, an average of 6 months ]
  GMT and four-fold seroconversion rate of binding antibodies (bAb's) IgA and IgG against spike protein across the three groups. Immune response (binding/ or neutralization) to the vector will be assessed by ELISA
• Vaccine induced cell mediated antigen specific T-cell responses across the three groups. [ Time Frame: Through study completion, an average of 6 months ]
  IFN-gamma (ELISPOT)
• Vaccine induced cell mediated antigen specific cytokines across the three groups. To evaluate the vaccine induced Cell mediated immune response. [ Time Frame: Through study completion, an average of 6 months ]
  Th1/Th2 profiling
• To evaluate the vaccine secretory IgA antibody response. [ Time Frame: Through study completion, an average of 6 months ]
• To evaluate the safety of the vaccine in terms of assessing adverse event of special interest (AESI) [ Time Frame: Through study completion, an average of 6 months ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of an Intranasal SARS-CoV-2 Vaccine (BBV154) for COVID-19
• Official Title: A Phase 1, Randomized, Double-blinded, Multicenter Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of an Intranasal Adenovirus Vector COVID-19 Vaccine (BBV154) in Healthy Volunteers

Brief Summary

The study is designed to evaluate the safety, reactogenicity, and immunogenicity of three groups of healthy volunteers who receive either intranasal single dose (vaccine on Day 0 and placebo on Day 28) or two-dose (vaccine on Day 0 and 28) of BBV154 vaccine or Placebo (on Day 0 and day 28). A total of 175 subjects will be enrolled in 2:2:1 ratio and will be conducted in a double-blinded manner.

To assess the safety of the vaccine, each participant will record symptoms in a diary card for 7 days after each dose. Safety and laboratory tests and physical exams will also be performed.

Blood samples and saliva samples be collected to assess the immune response from the vaccine.

An interim report based on the safety and immunogenicity of the vaccine (BBV154) will be notified to the Central Drugs Standard Control Organization (CDSCO), India, for further progressing the clinical development of the vaccine. This unblinded interim report will contain a detailed analysis of the data based on the primary and secondary objectives of all visits through Day 42 (Immunogenicity & Safety).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

A Phase 1, Randomized, Double-blinded, Multicenter Study to Evaluate the Reactogenicity, Safety, and Immunogenicity of an Intranasal Adenoviral vector COVID-19 vaccine (BBV154) in Healthy Volunteers.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The vaccine and placebo are identical in appearance and colour.

Primary Purpose: Prevention

• Condition: SARS-CoV Infection

Intervention

• Biological: BBV154 Vaccine
  Replication deficient Adenoviral vector-based (expressing a stabilized spike protein) SARS-CoV-2 vaccine (BBV154) NLT 1X10^10 Virus Particle.
• Biological: Placebo
  Placebo

Study Arms

• Experimental: BBV154: Single Dose
  Group 1 (Single dose group): In this group, 70 participants will be recruited and administered with vaccine (BBV154) on day 0 and with placebo on day 28 via intranasal route.
  Intervention: Biological: BBV154 Vaccine
• Experimental: BBV154: Two Dose
  Group 2 (Two-dose group): In this group, 70 participants will be recruited and administered with vaccine (BBV154) on both day 0 and on day 28 via intranasal route.
  Intervention: Biological: BBV154 Vaccine
• Placebo Comparator: Placebo
  Group 3 (Placebo): In this group, 35 participants will be recruited and administered with placebo on both day 0 and day 28 via intranasal route.
  Intervention: Biological: Placebo

• Publications *: Hassan AO, Kafai NM, Dmitriev IP, Fox JM, Smith BK, Harvey IB, Chen RE, Winkler ES, Wessel AW, Case JB, Kashentseva E, McCune BT, Bailey AL, Zhao H, VanBlargan LA, Dai YN, Ma M, Adams LJ, Shrihari S, Danis JE, Gralinski LE, Hou YJ, Schafer A, Kim AS, Keeler SP, Weiskopf D, Baric RS, Holtzman MJ, Fremont DH, Curiel DT, Diamond MS. A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2. Cell. 2020 Oct 1;183(1):169-184.e13. doi: 10.1016/j.cell.2020.08.026. Epub 2020 Aug 19.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 11, 2021): 175
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: November 30, 2021
• Actual Primary Completion Date: June 25, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Ability to provide written informed consent.
2. Participants of either gender of age between ≥18 to ≤60 years.
3. Good general health as determined by the discretion of investigator (vital signs (heart rate ≥60 to≤100 bpm; blood pressure systolic ≥90 mm Hg and <140 mm Hg; diastolic ≥ 60 mm Hg and <90 mm Hg; oral temperature <100.4ºF), medical history, and physical examination).
4. Expressed interest and availability to fulfil the study requirements.
5. For a female participant of child-bearing potential, planning to avoid becoming pregnant (use of an effective method of contraception or abstinence) from the time of study enrolment until at least four weeks after the last vaccination.
6. Male subjects of reproductive potential: Use of condoms to ensure effective contraception with the female partner from first vaccination until 3 months after last vaccination.
7. Male subjects agree to refrain from sperm donation from the time of first vaccination until 3 months after last vaccination.
8. Participants must refrain from blood or plasma donation from the time of first vaccination until 3 months after last vaccination.
9. Agrees not to participate in another clinical trial at any time during the study period.
10. Agrees to remain in the study area for the entire duration of the study.
11. Willing to allow storage and future use of biological samples for future research.

Exclusion Criteria:

1. History of any other COVID-19 investigational/or licensed vaccination.

2. Unacceptable laboratory abnormality from screening (prior to first vaccination) or safety testing, as listed below [Abnormal Complete Blood Count (CBC), Random blood sugar level, Renal function test (serum urea and Creatinine), liver function tests, urine analysis report, Positive serology for hepatitis C or HIV antibody or hepatitis B surface antigen].

   (Subjects will be informed if their results are positive for hepatitis C, HIV 1 & 2 antibody or hepatitis B surface antigen (HBsAg) and will be referred to a primary care provider for follow up of these abnormal laboratory tests.)

3. Confirmed SARS-CoV-2 at the time of screening using RT-PCR and ELISA or CLIA method.
4. History of facial nerve paralysis
5. History of cold, sneezing, nasal obstruction in the past 3 days.
6. Prescribed usage of any nasal spray/or nasal drop medication.
7. Any significant abnormality altering the anatomy of the nose in a substantial way or nasopharynx that may interfere with the aims of the study and in particular any of the nasal assessments or viral challenge (historical nasal polyps can be included, but large nasal polyps causing current and significant symptoms and/or requiring regular treatments in the last month are excluded)
8. For women of child bearing potential, a positive serum pregnancy test (during screening within 45 days of enrolment) or positive urine pregnancy test (within 24 hours of administering each dose of vaccine).
9. Temperature >38.0°C (100.4°F) or symptoms of an acute self-limited illness such as an upper respiratory infection or gastroenteritis within three days prior to each dose of vaccine.
10. Medical problems as a result of alcohol or illicit drug use during the past 12 months.
11. Receipt of an experimental agent (vaccine, drug, device, etc.) within 60 days before enrolment or expects to receive an investigational agent during the study period.
12. Receipt of any licensed vaccine within four weeks before enrolment in this study.
13. Known sensitivity to any ingredient of the study vaccines, or a more severe allergic reaction and history of allergies in the past.
14. Receipt of immunoglobulin or other blood products within the three months prior to vaccination in this study.
15. Immunosuppression as a result of an underlying illness or treatment with immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation therapy within the preceding 36 months.
16. Long-term use (> 2 weeks) of oral or parenteral steroids (glucocorticoids) or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding six months (nasal and topical steroids are allowed).
17. Any history of hereditary angioedema or idiopathic angioedema.
18. Any history of anaphylaxis in relation to vaccination.
19. Any history of albumin-intolerance.
20. Pregnancy, lactation, or willingness/intention to become pregnant during the study.
21. History of any cancer.
22. History of severe psychiatric conditions likely to affect participation in the study.
23. A bleeding disorder (e.g. factor deficiency, coagulopathy or platelet disorder, or prior history of significant bleeding or bruising following IM injections or venepuncture.
24. Any other serious chronic illness requiring hospital specialist supervision.
25. Chronic respiratory diseases like severe acute respiratory syndrome (SARS), including mild asthma.
26. Chronic cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, and neurological illness
27. Morbidly obese (BMI≥35 kg/m2) or underweight (BMI ≤18 kg/m2).
28. Living in the same household of any COVID-19 positive person.
29. Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol. Re-Vaccination Exclusion Criteri.
30. Pregnancy.
31. Anaphylactic reaction following administration of the investigational vaccine.
32. Virologically confirmed cases of SARS-CoV-2 infection.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India

Administrative Information

• NCT Number: NCT04751682
• Other Study ID Numbers: BBIL/BBV154/2020
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bharat Biotech International Limited
• Original Responsible Party: Same as current
• Current Study Sponsor: Bharat Biotech International Limited
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Bharat Biotech International Limited
• Verification Date: August 2022