TyphoidPhase 3NCT03933098
Immune Non-inferiority and Safety of a Vi-DT Typhoid Conjugate Vaccine
A Phase 3 study testing Test Vaccine Vi-DT Typhoid conjugate in people with Typhoid, run by International Vaccine Institute at 4 sites in Nepal.
Trial summary
This is a Multicenter, observer-blinded, randomized, Active controlled, Phase 3 study in healthy 6 months to 45 years aged Nepalese at the time of the first vaccine dose. The study objectives are: I. Read more about this study
- Who is it for?
- Ages 6 months to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Typhoid
- What is being tested?
- Test Vaccine Vi-DT Typhoid conjugate
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,800 participants
- Where
- 4 sitesNepal
- Study dates
- 15 Nov 2019to Jan 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 45 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Healthy participants 6 months to 45 years of age at enrollment
- Participants/Parents/LAR who have voluntarily given informed consent/assent
- Participants/Parents/LAR willing to follow the study procedures of the study and available for the entire duration of the study
Who cannot join
- Child with a congenital abnormality
- Subject concomitantly enrolled or scheduled to be enrolled in another trial
- Known history of immune function disorders including immunodeficiency diseases (Known HIV infection or other immune function disorders)
- Chronic use of systemic steroids (>2 mg/kg/day or >20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs
- Receipt of blood or blood-derived products in the past 3 months
- Subject with a previously ascertained or suspected disease caused by S. Typhi
Show all 18Show fewer
- Subject who have had household contact with/and or intimate exposure to an individual with laboratory-confirmed S. Typhi
- Individual who has previously received a typhoid vaccine
- Subject who has received or is expected to receive other vaccines from 1 month prior to IP vaccination to Visit 4 (approx.1 month post IP) except PVC booster as per EPI schedule
- Known history or allergy to vaccines or other medications
- History of uncontrolled coagulopathy or blood disorders
- Any abnormality or chronic disease which in the opinion of the investigator might be detrimental for the safety of the subject and interfere with the assessment of the study objectives
- Any female participant who is lactating, pregnant* or planning for pregnancy during the course of study period
- Participants/Parents/LAR planning to move from the study area before the end of study period
- As per Investigator's medical judgement individuals could be excluded from the study inspite of meeting all inclusion/exclusion criteria mentioned above
- Temporary Contraindication
- Acute illness, in particular infectious disease or fever (axillary temperature ≥37.5°C), within three days prior to enrolment and vaccination.
- Urine pregnancy test (UPT) will be performed in all married females prior to injection
Trial locations and contacts
4 sites in 1 country.
Nepal4 sites
Nepalgunj medical college
Bānke, City- Nepalgunj
Kanti Children's Hospital
Kathmandu, Sukedhara, 44600
Dhulikhel Hospital
Kavre, Dhulikhel
B.P.Koirala Institute of Health Sciences
Rautahat, Dharan
About this study
Official title: A Phase III Multicenter, Observer-Blinded, Randomized, Active Controlled, Immune Non-inferiority and Safety Study of Vi-DT Vaccine Compared to Typbar TCV® in Healthy 6 Months-45 Years Aged Nepalese Participants.
This is a Multicenter, observer-blinded, randomized, Active controlled, Phase 3 study in healthy 6 months to 45 years aged Nepalese at the time of the first vaccine dose.
The study objectives are:
- Demonstrate non-inferiority of Vi-DT compared to Typbar TCV® as measured by seroconversion rates of anti-Vi IgG ELISA antibody titers, 4 weeks after single dose (pooled immunogenicity of three lots of Vi-DT)
II. Demonstrate the equivalence of immunogenicity as measured by anti-Vi IgG GMT of three lots of Vi-DT vaccine 4 weeks after single dose.
Read the detailed description
Subjects will be stratified according to age. The study procedure is as follows:
Visit 1 (day-1 to -7): Screen participants by medical/medications history, physical examination, Vital signs, Urine pregnancy test (UPT)
Visit 2 (day 0): Enroll, randomize and administer vaccine to eligible participants and assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments.
Visit 3 (day 7): Check solicited adverse reaction 7 days post vaccination and Assess participant safety by physical examination and Vital signs
Visit 4 (day 28): Assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments
Visit 5 (day 84): Assess participant safety by physical examination and Vital signs
Visit 6 (day 168): Assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments, and fill in study completion form in the absence of any safety concern.
This study is observer-blind: vaccine administrator and vaccine safety evaluator will be two distinct persons to avoid bias of safety assessment. Trial staff other than the vaccine administrator.
For retention: After vaccination, field health worker/designee will contact participant every day till Day 7 by physical visit or by phone call. Follow-up reminder calls will be done very frequently as per discretion of study staff until 24 weeks for all participant to assess participant safety.
- Conditions
- Typhoid
- Being tested
- Test Vaccine Vi-DT Typhoid conjugate, Control Vaccine Typbar TCV®
- Keywords
- Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicity
- Medical subject headings
- Typhoid Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Test Vaccine Vi-DT Typhoid conjugateBiological
Also called Vi-DT Typhoid conjugate vaccine
- Manufacturer: SK Bioscience Co., Ltd.
- Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid
- Dose: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial
Control Vaccine Typbar TCV®Biological
Also called Typbar TCV®
- Manufacturer: Bharat Biotech
- Ingredient: Purified Vi capsular polysaccharide of Salmonella Ty2 conjugated to tetanus toxoid protein
- Dose: 0.5 ml
| Study group | Role | What they receive |
|---|---|---|
| Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine) | Experimental | One dose of Vi-DT (typhoid conjugate vaccine) Lot 1 will be administrated intramuscularly at Enrollment visit (Day 0).
MR for age group at 9-15 months. Receives: Biological: Test Vaccine Vi-DT Typhoid conjugate |
| Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine) | Experimental | One dose of Vi-DT (typhoid conjugate vaccine) Lot 2 will be administrated intramuscularly at Enrollment visit (Day 0).
MR for age group at 9-15 months. Receives: Biological: Test Vaccine Vi-DT Typhoid conjugate |
| Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine) | Experimental | One dose of Vi-DT (typhoid conjugate vaccine) Lot 3 will be administrated intramuscularly at Enrollment visit (Day 0).
MR for age group at 9-15 months. Receives: Biological: Test Vaccine Vi-DT Typhoid conjugate |
| Test group D: Typbar TCV | Active comparator | One dose of Typbar TCV will be administrated intramuscularly at Enrollment visit (Day 0).
MR for age group at 9-15 months. Receives: Biological: Control Vaccine Typbar TCV® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seroconversion rate1
Defined as a 4-fold increase of serum anti-Vi IgG antibody titer
Measured: 4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)
Geometric Mean Titers (GMT)1
Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT
Measured: 4 weeks after vaccination of Vi-DT
Secondary outcomes (6)
Geometric Mean Titers (GMT) 2
Measurement of the Geometric Mean Titers (GMT) following 4 weeks (28 days) and 24 weeks(168 days) after vaccination of Vi-DT (pooled)/ Typbar TCV®
Measured: 4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV®
Seroconversion rate 2
Defined as a 4-fold increase of serum anti-Vi IgG antibody titer
Measured: 24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0).
Seroconversion rate 3
Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers after vaccination of three lots of Vi-DT.
Measured: 4 weeks (28 days) after vaccination of Vi-DT(pooled)
Seroconversion rate 4
Definded as a Seroconversion rates of anti-Vi IgG ELISA antibody titers at 4 weeks (28 days) after vaccination of three lots of Vi-DT in each age strata
Measured: 4 weeks (28 days) after vaccination of Vi-DT(pooled)
Seroconversion rate 5
Definded as IgG ELISA antibody titers for Measles (M), and Rubella (R) following single dose of MR a vaccine at baseline D0 and 4 weeks
Measured: 4 weeks (28 days) after vaccination of MR compared to baseline (D0)
Safety endpoints for solicited adverse events (reactogenicity)
Proportion of participants with local and systemic solicited adverse events
Measured: 7days after vaccination of Vi-DT(pooled)/ Typbar TCV®
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2019
- Study start15 Nov 2019
- Primary completionSep 2020 (estimated)
- Study completionJan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for TyphoidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants age 6 months to 45 years
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- International Vaccine Institute
- Sponsor type
- University, hospital or other
- Collaborators
- SK Bioscience Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Ganesh Kumar Rai, MD, Principal investigator, Kanti Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03933098
- Sponsor's protocol ID
- IVI T003
- Status last verified
- Apr 2020
- First submitted
- 26 Apr 2019
- Last updated
- 22 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kumar Rai G, Saluja T, Chaudhary S, Tamrakar D, Kanodia P, Giri BR, Shrestha R, Uranw S, Kim DR, Yang JS, Park IY, Kyung SE, Vemula S, Reddy E J, Kim B, Gupta BP, Jo SK, Ryu JH, Park HK, Shin JH, Lee Y, Kim H, Kim JH, Mojares ZR, Wartel TA, Sahastrabuddhe S. Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial. Lancet Infect Dis. 2022 Apr;22(4):529-540. doi: 10.1016/S1473-3099(21)00455-2. Epub 2021 Dec 20.
PubMed 34942090
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Multicenter, Observer-Blinded, Randomized, Active Controlled, Immune Non-inferiority and Safety Study of Vi-DT Vaccine Compared to Typbar TCV® in Healthy 6 Months-45 Years Aged Nepalese Participants.
- ClinicalTrials.gov ID
- NCT03933098
- Acronym / sponsor ID
- IVI T003
- Conditions
- Typhoid
- Keywords
- Typhoid conjugate vaccine, Vi-DT, Safety, Immunogenicity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,800 participants (estimated)
- Lead sponsor
- International Vaccine InstituteUniversity, hospital or other
- Collaborators
- SK Bioscience Co., Ltd.
- Study start
- 15 Nov 2019 (actual)
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Jan 2021 (estimated)
- First posted
- 1 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Multicenter, observer-blinded, randomized, Active controlled, Phase 3 study in healthy 6 months to 45 years aged Nepalese at the time of the first vaccine dose.
The study objectives are:
- Demonstrate non-inferiority of Vi-DT compared to Typbar TCV® as measured by seroconversion rates of anti-Vi IgG ELISA antibody titers, 4 weeks after single dose (pooled immunogenicity of three lots of Vi-DT)
II. Demonstrate the equivalence of immunogenicity as measured by anti-Vi IgG GMT of three lots of Vi-DT vaccine 4 weeks after single dose.
Detailed description
Subjects will be stratified according to age. The study procedure is as follows:
Visit 1 (day-1 to -7): Screen participants by medical/medications history, physical examination, Vital signs, Urine pregnancy test (UPT)
Visit 2 (day 0): Enroll, randomize and administer vaccine to eligible participants and assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments.
Visit 3 (day 7): Check solicited adverse reaction 7 days post vaccination and Assess participant safety by physical examination and Vital signs
Visit 4 (day 28): Assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments
Visit 5 (day 84): Assess participant safety by physical examination and Vital signs
Visit 6 (day 168): Assess participant safety by physical examination and Vital signs, Collect blood for immunogenicity assessments, and fill in study completion form in the absence of any safety concern.
This study is observer-blind: vaccine administrator and vaccine safety evaluator will be two distinct persons to avoid bias of safety assessment. Trial staff other than the vaccine administrator.
For retention: After vaccination, field health worker/designee will contact participant every day till Day 7 by physical visit or by phone call. Follow-up reminder calls will be done very frequently as per discretion of study staff until 24 weeks for all participant to assess participant safety.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Participants age 6 months to 45 years
| Arm | Type | Receives |
|---|---|---|
| Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine) | Experimental | Biological: Test Vaccine Vi-DT Typhoid conjugateOne dose of Vi-DT (typhoid conjugate vaccine) Lot 1 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. |
| Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine) | Experimental | Biological: Test Vaccine Vi-DT Typhoid conjugateOne dose of Vi-DT (typhoid conjugate vaccine) Lot 2 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. |
| Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine) | Experimental | Biological: Test Vaccine Vi-DT Typhoid conjugateOne dose of Vi-DT (typhoid conjugate vaccine) Lot 3 will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. |
| Test group D: Typbar TCV | Active comparator | Biological: Control Vaccine Typbar TCV®One dose of Typbar TCV will be administrated intramuscularly at Enrollment visit (Day 0). MR for age group at 9-15 months. |
Who may qualify
- Ages
- 6 months to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Healthy participants 6 months to 45 years of age at enrollment
- Participants/Parents/LAR who have voluntarily given informed consent/assent
- Participants/Parents/LAR willing to follow the study procedures of the study and available for the entire duration of the study
Key exclusion criteria (18 listed)
- Child with a congenital abnormality
- Subject concomitantly enrolled or scheduled to be enrolled in another trial
- Known history of immune function disorders including immunodeficiency diseases (Known HIV infection or other immune function disorders)
- Chronic use of systemic steroids (>2 mg/kg/day or >20 mg/day prednisone equivalent for periods exceeding 10 days), cytotoxic or other immunosuppressive drugs
- Receipt of blood or blood-derived products in the past 3 months
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Test Vaccine Vi-DT Typhoid conjugateAlso: Vi-DT Typhoid conjugate vaccine* Manufacturer: SK Bioscience Co., Ltd. * Ingredient: Purified Vi-polysaccharide conjugated to diphtheria toxoid * Dose: 25 µg of Vi polysaccharide/0.5 mL, presented in 3 mL multi-dose glass vial | Biological | Test group A: Lot 1 Vi-DT (typhoid conjugate vaccine), Test group B: Lot 2 Vi-DT (typhoid conjugate vaccine), Test group C: Lot 3 Vi-DT (typhoid conjugate vaccine) |
| Control Vaccine Typbar TCV®Also: Typbar TCV®* Manufacturer: Bharat Biotech * Ingredient: Purified Vi capsular polysaccharide of Salmonella Ty2 conjugated to tetanus toxoid protein * Dose: 0.5 ml | Biological | Test group D: Typbar TCV |
Primary outcome
Seroconversion rate1
Time frame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)
Defined as a 4-fold increase of serum anti-Vi IgG antibody titer
Geometric Mean Titers (GMT)1
Time frame: 4 weeks after vaccination of Vi-DT
Measurement of the Geometric Mean Titers (GMT) following 4 weeks after vaccination of three lots of Vi-DT
6 secondary outcomes
Geometric Mean Titers (GMT) 2
Time frame: 4 weeks and 24 weeks after vaccination of Vi-DT(pooled)/ Typbar TCV®
Seroconversion rate 2
Time frame: 24 weeks (168 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0).
Seroconversion rate 3
Time frame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)
Seroconversion rate 4
Time frame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)
Seroconversion rate 5
Time frame: 4 weeks (28 days) after vaccination of MR compared to baseline (D0)
Safety endpoints for solicited adverse events (reactogenicity)
Time frame: 7days after vaccination of Vi-DT(pooled)/ Typbar TCV®
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2020.
- Derived from this study: PubMed 34942090Kumar Rai G, Saluja T, Chaudhary S, Tamrakar D, Kanodia P, Giri BR, Shrestha R, Uranw S, Kim DR, Yang JS, Park IY, Kyung SE, Vemula S, Reddy E J, Kim B, Gupta BP, Jo SK, Ryu JH, Park HK, Shin JH, Lee Y, Kim H, Kim JH, Mojares ZR, Wartel TA, Sahastrabuddhe S. Safety and immunogenicity of the Vi-DT typhoid conjugate vaccine in healthy volunteers in Nepal: an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial. Lancet Infect Dis. 2022 Apr;22(4):529-540. doi: 10.1016/S1473-3099(21)00455-2. Epub 2021 Dec 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ganesh Kumar Rai, MD principal investigator
Kanti Children's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Test Vaccine Vi-DT Typhoid conjugate in people with Typhoid, run by International Vaccine Institute at 4 sites in Nepal.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Nepal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Seroconversion rate1 (time frame: 4 weeks (28 days) after vaccination of Vi-DT(pooled)/ Typbar TCV® compared to baseline (D0)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03933098, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2020.