An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers

• ClinicalTrials.gov Identifier: NCT04641481
• Recruitment Status: Active, not recruiting
• First Posted: November 23, 2020
• Last Update Posted: March 19, 2021
• Sponsor: Bharat Biotech International Limited
• Collaborators: Indian Council of Medical Research; Iqvia Pty Ltd
• Information provided by (Responsible Party): Bharat Biotech International Limited

Tracking Information

• First Submitted Date: November 9, 2020
• First Posted Date: November 23, 2020
• Last Update Posted Date: March 19, 2021
• Actual Study Start Date: November 16, 2020
• Actual Primary Completion Date: January 8, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2020)

First occurrence of Virologically confirmed (RT-PCR positive) symptomatic cases of COVID-19. [ Time Frame: Day 42 to Month 12 ]

(RT-PCR positive) symptomatic cases of COVID-19.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 20, 2020)

• First occurence of Virologically confirmed (RT-PCR positive) symptomatic cases of COVID-19 based on the case definition for the secondary efficacy symptomatic endpoint. [ Time Frame: Day 42 to Month 12 ]
  (RT-PCR positive) symptomatic cases of COVID-19.
• Virologically confirmed (RT-PCR positive) severe cases of COVID-19 [ Time Frame: Day 42 to Month 12 ]
  (RT-PCR positive) severe symptomatic cases of COVID-19.
• Virologically confirmed COVID-19 cases of any severity occurring among participants 18 through 59 years of age and ≥60 years of age. [ Time Frame: Day 42 to Month 12 ]
  (RT-PCR positive) symptomatic cases of COVID-19
• Virologically confirmed COVID-19 asymptomatic and symptomatic cases occurring from two weeks after the second vaccination. [ Time Frame: Day 42 to Month 12 ]
  (RT-PCR positive) asymptomatic/symptomatic cases of COVID-19.
• Reactogenicity and Safety [ Time Frame: Day 42 to Month 12 ]
  Solicited, Unsolicited, Serious Adverse Events
• The occurrence of enhanced respiratory disease episodes. [ Time Frame: Day 42 to Month 12 ]
  Reported by participant/documented in hospital records throughout the trial.
• Immunogenicity: Lot-to-Lot consistency of three consecutive GMP Lots [ Time Frame: Day 0 to Day 42 ]
  Assessed based Wild-type SARS-CoV-2 Specific Neutralizing Antibody (nAb)
• Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb) [ Time Frame: Day 0 to Month 12 ]
  Specific Neutralizing Antibody (nAb)

• 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: An Efficacy and Safety Clinical Trial of an Investigational COVID-19 Vaccine (BBV152) in Adult Volunteers
• Official Title: An Event-Driven, Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate Efficacy, Safety, Immunogenicity, Lot-to-Lot Consistency of BBV152, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Adults≥18 Yrs of Age
• Brief Summary: The BBV152 vaccine is being developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. The study is designed to primarily evaluate the efficacy, safety, and immunogenicity of BBV152 to prevent COVID-19 for up to 1 year after the second dose of BBV152.

Detailed Description

This is a phase 3 Event-Driven, randomized, double-blind, placebo-controlled, multicentre study to Evaluate the Efficacy, Safety, and Immunogenicity of BBV152, a Whole-Virion Inactivated SARS-CoV-2 Vaccine in Volunteers aged 18 years and above.

A total of 25,800 subjects will be enrolled and randomized in a 1:1 ratio to receive the BBV152 vaccine and control. All participants will be assessed for efficacy and safety endpoints and provide a Nasopharyngeal(NP) swab and blood sample before the first dose of IP. The NP swab and blood collected will be subject to RT-PCR and Anti-SARS-CoV-2 IgG antibodies. The results of this will not affect the enrollment of the participant. Participants who are found to be positive for either RT-PCR Or Anti-SARS-CoV-2 IgG antibodies will be excluded from the primary efficacy analysis. A safety follow-up will be done for all.

In addition, sites will be segregated based on the study objectives:

Category 1 (Symptomatic): In addition to administering the IP, a series of post-dose telephonic follow-up visits will be scheduled to detect suspect symptomatic COVID-19 infections. If a suspect is identified, a nasopharyngeal sample will be collected from the participant for detecting the presence of COVID-19 infection. Telephonic follow-up will occur at 15 Day intervals.

Category 2 (Symptomatic/Asymptomatic): In addition to administering the IP, a series of post-dose Nasopharyngeal samples for detecting an incidence of asymptomatic COVID-19 infection at 1-Month intervals will be collected.

Category 3 (Symptomatic/Asymptomatic+Immunogenicity): In addition to administering the IP and collecting NP samples, a series of blood samples will be collected for analyzing serum for immunological assessments.

The Phase 3 study will follow randomized study participants for efficacy until virologically confirmed (RT-PCR positive) symptomatic COVID-19 participants will be eligible for the primary efficacy analysis. After reaching the target number (n=130) of symptomatic COVID-19 cases, the study will continue to assess safety until the completion of the study duration. It is planned to continue the Phase 3 trial until 130 study participants in the per-protocol population develop PCR-confirmed symptomatic COVID-19 disease during follow-up beginning 14 days after the second dose of vaccine or placebo. We estimate that approximately 25,800 participants should be randomized to accrue these 130 events. The Lot-to-Lot consistency (Immunogenicity) study will be nested within the Phase 3 (Efficacy) study (in three selected sites). The Immunogenicity study will assess the immune response of a 2-dose regimen of BBV152B vaccine through geometric mean titers (GMTs) by neutralizing antibody, S-protein, and RBD specific anti-IgG binding titer in a subset of 600 (450 vaccine: 150 placebo) participants, across three consecutive manufacturing Lots. Data generated through Day 56 (Month 2) will be unblinded only to the biostatistician for evaluation of immune responses in the Immunogenicity subset.

Formal interim analyses are planned when approximately 1/3 and 2/3 of the target number of participants with confirmed symptomatic COVID-19 have been accrued, to determine whether the sample size and/or length of follow-up should be increased. This interim report containing safety and immunogenicity data will be submitted to CDSCO.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

All vaccine and placebo formulations are at a volume of 0.5mL per dose filled into a single-use glass vial. The appearance, color, and viscosity are identical across all vaccine and control formulations.

Participants, investigators, study coordinators, study-related personnel, and the sponsor will be blinded to the treatment group allocation (excluding an unblinded CRO, who is tasked with the dispatch and labeling of vaccine vials and the generation of the master randomization code). Participants will be assigned a computer-generated randomization code that maintains blinding. The blinded study nurse is responsible for vaccine preparation and administration. Each vial contains a unique code that ensured appropriate blinding.

Primary Purpose: Prevention

Condition

• Covid19
• SARS-CoV Infection

Intervention

• Biological: BBV152
  BBV152 (6µg-Algel - Imidazoquinoline)
• Biological: Placebo
  Placebo (PBS+Alum, without antigen)

Study Arms

• Experimental: Study vaccine
  BBV152B (6µg-Algel-IMDG)
  Intervention: Biological: BBV152
• Placebo Comparator: Placebo
  Phosphate buffered saline with Alum (without antigen)
  Intervention: Biological: Placebo

• Publications *: Ella R, Reddy S, Blackwelder W, Potdar V, Yadav P, Sarangi V, Aileni VK, Kanungo S, Rai S, Reddy P, Verma S, Singh C, Redkar S, Mohapatra S, Pandey A, Ranganadin P, Gumashta R, Multani M, Mohammad S, Bhatt P, Kumari L, Sapkal G, Gupta N, Abraham P, Panda S, Prasad S, Bhargava B, Ella K, Vadrevu KM; COVAXIN Study Group. Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial. Lancet. 2021 Dec 11;398(10317):2173-2184. doi: 10.1016/S0140-6736(21)02000-6. Epub 2021 Nov 11.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: November 20, 2020): 25800
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2022
• Actual Primary Completion Date: January 8, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Ability to provide written informed consent and availability to fulfill the study requirements.
• Participants of either gender of aged 18 years and above.
• Participants with good general health as determined by the discretion of the investigator, or participants with stable medical conditions. A stable medical condition is defined as a disease not requiring significant change in therapy or hospitalization or worsening disease during the 3 months before enrolment.
• 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 eight weeks after the last vaccination.
• Male subjects of reproductive potential: Use of condoms to ensure effective contraception with the female partner and to refrain from sperm donation from first vaccination until at least 3 months after the last vaccination.
• Agrees not to participate in another clinical trial at any time during the study period.
• Agrees not to take any COVID-19 licensed vaccination for the entire duration of the study.
• Agrees to remain in the study area for the entire duration of the study.
• Willing to allow storage and future use of biological samples for future research

Exclusion Criteria:

• History of any other COVID-19 investigational or licensed vaccination.
• Known history of SARS-CoV-2 infection, as declared by the subject.
• For women, positive urine pregnancy test before the first dose of vaccination, or any time during the study period.
• 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.
• Resident of COVID-19 infection in the same household.
• Known case of HIV, hepatitis B, or hepatitis C infection.
• Receipt of any licensed/experimental vaccine within four weeks before enrolment in this study.
• Receipt of immunoglobulin or other blood products within the three months before vaccination in this study.
• 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.
• Immunoglobulins, anti-cytokine antibodies, and blood products within 6 months prior to study vaccination, during, and 21 days following the last dose of vaccination.
• Pregnancy, lactation, or willingness/intention to become pregnant during the first 6 months after enrolment.
• Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, an endocrine disorder, and neurological illness (mild/moderate well-controlled comorbidities are allowed)

Re-Vaccination Exclusion Criteria

• Pregnancy.
• History of virologically (RT-PCR) confirmed SARS-CoV-2 infection
• Anaphylactic reaction following administration of the investigational vaccine.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 99 Years (Adult, Older 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: NCT04641481
• Other Study ID Numbers: BBIL/BBV152-C/2020; BBIL/BBV152-C/2020 ( Other Identifier: Bharat Biotech International Ltd )
• 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

• Indian Council of Medical Research
• Iqvia Pty Ltd

Investigators

• Principal Investigator: Dr Chadramani Singh; All India Institute of Medical Sciences, Patna
• Principal Investigator: Dr Sanjay Kumar Rai; All India Institute of Medical Sciences Delhi
• Principal Investigator: Dr Azhar Ali Khan; Baba Raghav Das Medical Gorakhpur
• Principal Investigator: DrAnil Kumar Pandey; ESIC Medical College and Hospital Faridabad
• Principal Investigator: Dr Simmi Dube; Gandhi Medical College, Bhopal
• Principal Investigator: Dr Anjan Jyoti Talukdar; Gauhati Medical College & Hospital Assam
• Principal Investigator: Dr Priti Meshram; Grant Government Medical College and Sir J.J. Group of Hospitals Mumbai
• Principal Investigator: Dr Laxmi S Kumari; Guntur Medical College ,Guntur
• Principal Investigator: Dr Shiva Narang; Guru Teg Bahadur Hospital
• Principal Investigator: Dr E Venkat Rao; Institute of Medical Sciences and SUM Hospital Odisha
• Principal Investigator: Dr P Venugopal; King George Hospital Visakhapatnam
• Principal Investigator: Dr. N.T. Awad; Lokamanya tilak Municipal Medical College and General hospital Mumbai
• Principal Investigator: Dr Pajanivel Ranganadin; Mahatma Gandhi Medical College& Research Institute Pondicherry
• Principal Investigator: Dr Prabhakar Reddy; Nizam's Institute of Medical Sciences Hyderabad
• Principal Investigator: Dr Raghavendra Gumashta; Peoples university Bhopal
• Principal Investigator: Dr Tapan Kumar Saikia; Prince Aly Khan Hospital Mumbai
• Principal Investigator: Dr Savita Verma; Pt BO Sharma,PGIMS/UHS. Rohtak, Haryana
• Principal Investigator: Dr Manish Multani; Rahate Surgical Hospital ,Nagpur
• Principal Investigator: Dr Sagar Vivek Redkar; Redkar Hospital and Research Centre Goa
• Principal Investigator: Dr Meghana Murthy; Vagus Super speciality hospital,Bangalore
• Principal Investigator: Dr Akshata; Vydehi Institute of Medical Sciences and Research Centre,Bangalore
• Principal Investigator: Dr T S Selvavinayagam; Directorate of Public Health and Preventive Medicine,Chennai
• Principal Investigator: Dr Suman Kanungo; ICMR-National Institute of Cholera and Enteric Diseases,West Bengal
• Principal Investigator: Dr Mohammad Shameem; Aligarh Muslim University,Uttar Pradesh
• Principal Investigator: Dr Parul Bhatt; Gmers Medical College and Civil Hospital,Ahmedabad

• PRS Account: Bharat Biotech International Limited
• Verification Date: March 2021