Clinical trial NCT04641481: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Covid19
SARS-CoV Infection
Lead sponsor: Bharat Biotech International Limited
Sponsor class: INDUSTRY
Collaborators: name: Indian Council of Medical Research
name: Iqvia Pty Ltd
First posted: 2020-11-23
Enrollment: 25800
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: First occurrence of Virologically confirmed (RT-PCR positive) symptomatic cases of COVID-19.
timeFrame: Day 42 to Month 12
Secondary outcomes:
measure: First occurence of Virologically confirmed (RT-PCR positive) symptomatic cases of COVID-19 based on the case definition for the secondary efficacy symptomatic endpoint.
timeFrame: Day 42 to Month 12
measure: Virologically confirmed (RT-PCR positive) severe cases of COVID-19
timeFrame: Day 42 to Month 12
measure: Virologically confirmed COVID-19 cases of any severity occurring among participants 18 through 59 years of age and ≥60 years of age.
timeFrame: Day 42 to Month 12
measure: Virologically confirmed COVID-19 asymptomatic and symptomatic cases occurring from two weeks after the second vaccination.
timeFrame: Day 42 to Month 12
measure: Reactogenicity and Safety
timeFrame: Day 42 to Month 12
measure: The occurrence of enhanced respiratory disease episodes.
timeFrame: Day 42 to Month 12
measure: Immunogenicity: Lot-to-Lot consistency of three consecutive GMP Lots
timeFrame: Day 0 to Day 42
measure: Geometric Mean Titer (GMT) of SARS-CoV-2 Specific Neutralizing Antibody (nAb)
timeFrame: Day 0 to Month 12
Other outcomes:
Locations:
city: Rohtak
country: India
facility: Pt BD SHARMA,PGIMS/UHS
state: Haryana
Study officials:
affiliation: All India Institute of Medical Sciences
name: Dr Chadramani Singh
role: PRINCIPAL_INVESTIGATOR
affiliation: All India Institute of Medical Sciences Delhi
name: Dr Sanjay Kumar Rai
role: PRINCIPAL_INVESTIGATOR
affiliation: Baba Raghav Das Medical Gorakhpur
name: Dr Azhar Ali Khan
role: PRINCIPAL_INVESTIGATOR
affiliation: ESIC Medical College and Hospital Faridabad
name: DrAnil Kumar Pandey
role: PRINCIPAL_INVESTIGATOR
affiliation: Gandhi Medical College, Bhopal
name: Dr Simmi Dube
role: PRINCIPAL_INVESTIGATOR
affiliation: Gauhati Medical College & Hospital Assam
name: Dr Anjan Jyoti Talukdar
role: PRINCIPAL_INVESTIGATOR
affiliation: Grant Government Medical College and Sir J.J. Group of Hospitals Mumbai
name: Dr Priti Meshram
role: PRINCIPAL_INVESTIGATOR
affiliation: Guntur Medical College ,Guntur
name: Dr Laxmi S Kumari
role: PRINCIPAL_INVESTIGATOR
affiliation: Guru Teg Bahadur Hospital
name: Dr Shiva Narang
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute of Medical Sciences and SUM Hospital Odisha
name: Dr E Venkat Rao
role: PRINCIPAL_INVESTIGATOR
affiliation: King George Hospital Visakhapatnam
name: Dr P Venugopal
role: PRINCIPAL_INVESTIGATOR
affiliation: Lokamanya tilak Municipal Medical College and General hospital Mumbai
name: Dr. N.T. Awad
role: PRINCIPAL_INVESTIGATOR
affiliation: Mahatma Gandhi Medical College& Research Institute Pondicherry
name: Dr Pajanivel Ranganadin
role: PRINCIPAL_INVESTIGATOR
affiliation: Nizam's Institute of Medical Sciences Hyderabad
name: Dr Prabhakar Reddy
role: PRINCIPAL_INVESTIGATOR
affiliation: Peoples university Bhopal
name: Dr Raghavendra Gumashta
role: PRINCIPAL_INVESTIGATOR
affiliation: Prince Aly Khan Hospital Mumbai
name: Dr Tapan Kumar Saikia
role: PRINCIPAL_INVESTIGATOR
affiliation: Pt BO Sharma,PGIMS/UHS. Rohtak, Haryana
name: Dr Savita Verma
role: PRINCIPAL_INVESTIGATOR
affiliation: Rahate Surgical Hospital ,Nagpur
name: Dr Manish Multani
role: PRINCIPAL_INVESTIGATOR
affiliation: Redkar Hospital and Research Centre Goa
name: Dr Sagar Vivek Redkar
role: PRINCIPAL_INVESTIGATOR
affiliation: Vagus Super speciality hospital,Bangalore
name: Dr Meghana Murthy
role: PRINCIPAL_INVESTIGATOR
affiliation: Vydehi Institute of Medical Sciences and Research Centre,Bangalore
name: Dr Akshata
role: PRINCIPAL_INVESTIGATOR
affiliation: Directorate of Public Health and Preventive Medicine,Chennai
name: Dr T S Selvavinayagam
role: PRINCIPAL_INVESTIGATOR
affiliation: ICMR-National Institute of Cholera and Enteric Diseases,West Bengal
name: Dr Suman Kanungo
role: PRINCIPAL_INVESTIGATOR
affiliation: Aligarh Muslim University,Uttar Pradesh
name: Dr Mohammad Shameem
role: PRINCIPAL_INVESTIGATOR
affiliation: Gmers Medical College and Civil Hospital,Ahmedabad
name: Dr Parul Bhatt
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.