Typhoid FeverPhase 2NCT01229176

Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants

A Phase 2 study testing Vi-CRM197 vaccine, Vi Polysaccharide (PS) vaccine and Pneumococcal conjugate vaccine in people with Typhoid Fever, run by Novartis at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This phase 2 trial is aimed to obtain information on the safety and immunogenicity of the Vi-CRM197 in subjects from various age groups in India and Pakistan where Typhoid Fever is highly endemic and an efficacious vaccine against this disease is very much needed. Read more about this study

Who is it for?: Ages 6 weeks to 45 yearsHealthy volunteers can take part
Conditions the study is for: Typhoid Fever
What is being tested?: Vi-CRM197 vaccine, Vi Polysaccharide (PS) vaccine and Pneumococcal conjugate vaccine
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 200 participants
Where: 2 sitesin 2 countries
Study dates: Mar 2011to Jun 2012
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 weeks to 45 years
All sexes
Healthy volunteers accepted
Child, Adult

Main eligibility criteria:

Subjects belonging to 4 age groups will be enrolled into the trial: adults (18 to 45 years of age), children (24 to 59 months of age), older infants (9 to 12 months of age at enrollment) and infants (6 weeks of age at enrolment).
Written informed consent will be obtained by the all subjects or their parents/ guardians (depending on the age group) before enrollment into the trial.
Only females with a negative pregnancy test and willing to participate in family planning consultations (organized by the site study team) will be allowed to participate to the trial.
Infants who have been vaccinated with 1 dose of BCG, HBV and OPV at birth can be enrolled into the trial, while infants who have received DTwP+HBV+Hib or OPV due at 6 weeks of age as per local EPI schedule cannot be enrolled into the trial.

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

India1 site

K.E.M. Hospital Research Centre
Pune, Maharashtra, 411011

Other trials in India

Pakistan1 site

The Aga Khan University Hospital
Karachi, 74800

Other trials in Pakistan

About this study

Official title: A Phase 2a, Randomized, Controlled, Observer Blind, Age De-Escalation, Multicenter and Multinational Study of the Safety, Reactogenicity and Immunogenicity of the NVGH Glycoconjugate Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants

Conditions: Typhoid Fever
Being tested: Vi-CRM197 vaccine, Vi Polysaccharide (PS) vaccine, Pneumococcal conjugate vaccine
Medical subject headings: Typhoid Fever

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Vi-CRM197 vaccineBiological
Vi Polysaccharide (PS) vaccineBiological
Also called Typherix
Pneumococcal conjugate vaccineBiological
Also called Prevenar 13

Study groups in NCT01229176
Study group	Role	What they receive
Vi-CRM, Adults	Experimental	Adults (18 to 45 years) receiving 1 dose of NVGH Vi-CRM197 vaccine Receives: Biological: Vi-CRM197 vaccine
Vi-PS, Adults	Active comparator	Adults (18 to 45 years) receiving 1 dose of licensed Vi Polysaccharide vaccine Receives: Biological: Vi Polysaccharide (PS) vaccine
Vi-CRM, Children	Experimental	Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Receives: Biological: Vi-CRM197 vaccine
Vi-PS, Children	Active comparator	Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine Receives: Biological: Vi Polysaccharide (PS) vaccine; Biological: Pneumococcal conjugate vaccine
Vi-CRM, Older infants	Experimental	Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Receives: Biological: Vi-CRM197 vaccine
PNC13, Older infants	Active comparator	Older Infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine Receives: Biological: Pneumococcal conjugate vaccine
Vi-CRM, Infants	Experimental	Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine Receives: Biological: Vi-CRM197 vaccine
PNC13, Infants	Active comparator	Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine Receives: Biological: Pneumococcal conjugate vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer
Measured: At 28 days after last vaccination as compared to baseline
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer
Measured: At 6 months after last vaccination as compared to baseline
Anti-Vi ELISA Geometric Mean Concentration (GMC)
Measured: At 28 days after last vaccination
Anti-Vi ELISA GMC
Measured: At 6 months after last vaccination

Secondary outcomes (1)

Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination
Solicited local reactions were: Adults, children, older infants, infants: erythema, induration and pain/tenderness at the injection site.
Solicited systemic reactions were: Adults: chills, malaise, myalgia, arthralgia, headache, fatigue, rash and fever.
Children, older infants and infants: lethargy, irritability, vomiting, diarrhoea, loss of appetite, rash and fever (and persistent crying in infants).
Measured: During the 7-day follow-up period after vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2011Jun 2012

First posted27 Oct 2010 (estimated)
Study startMar 2011
Primary completionJun 2012
Study completionJun 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Typhoid FeverStudies 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 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Participant
Enrolment: 200 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01229176
Sponsor's protocol ID: H01_02TP
Status last verified: Apr 2014
First submitted: 25 Oct 2010
Last updated: 1 May 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Bhutta ZA, Capeding MR, Bavdekar A, Marchetti E, Ariff S, Soofi SB, Anemona A, Habib MA, Alberto E, Juvekar S, Khan RM, Marhaba R, Ali N, Malubay N, Kawade A, Saul A, Martin LB, Podda A. Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials. Lancet Infect Dis. 2014 Feb;14(2):119-29. doi: 10.1016/S1473-3099(13)70241-X. Epub 2013 Nov 28.
PubMed 24290843

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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The Effects of Iron Treatment on Vaccine Immunogenicity in Kenyan Infants With Iron Deficiency
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Curcumin Extract Added to Ciprofloxacin for Typhoid Carriers Among Food Handlers of the Free Nutritious Meal Program
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RecruitingPhase 4
Opportunistic Pneumococcal Immunisation Trial in MALnutrition
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Active, not recruitingPhase 3
Clinical Efficacy of Typhoid Conjugate Vaccine (Vi-TCV) Among Children Age 9 Months Through 12 Years in Blantyre, Malawi
Typhoid
RecruitingPhase 4
CVD 38000: Study of Responses to Vaccination With Typhoid and/or Cholera
Typhoid and/or Cholera Vaccination

All Typhoid Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 1 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2a, Randomized, Controlled, Observer Blind, Age De-Escalation, Multicenter and Multinational Study of the Safety, Reactogenicity and Immunogenicity of the NVGH Glycoconjugate Vaccine Against S. Typhi in Adults, Children, Older Infants and Infants
ClinicalTrials.gov ID: NCT01229176
Acronym / sponsor ID: H01_02TP
Conditions: Typhoid Fever
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 200 participants (actual)
Lead sponsor: NovartisIndustry (pharma, biotech, devices)
Study start: Mar 2011
Primary completion: Jun 2012 (actual)
Study completion: Jun 2012 (actual)
First posted: 27 Oct 2010 (estimated)
Results: Posted 10 Apr 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Single blind (participant)
Number of arms: 8

Arm	Type	Receives
Vi-CRM, Adults	Experimental	Biological: Vi-CRM197 vaccineAdults (18 to 45 years) receiving 1 dose of NVGH Vi-CRM197 vaccine
Vi-PS, Adults	Active comparator	Biological: Vi Polysaccharide (PS) vaccineAdults (18 to 45 years) receiving 1 dose of licensed Vi Polysaccharide vaccine
Vi-CRM, Children	Experimental	Biological: Vi-CRM197 vaccineChildren (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Vi-PS, Children	Active comparator	Biological: Vi Polysaccharide (PS) vaccine, Biological: Pneumococcal conjugate vaccineChildren (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine
Vi-CRM, Older infants	Experimental	Biological: Vi-CRM197 vaccineOlder Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
PNC13, Older infants	Active comparator	Biological: Pneumococcal conjugate vaccineOlder Infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine
Vi-CRM, Infants	Experimental	Biological: Vi-CRM197 vaccineInfants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine
PNC13, Infants	Active comparator	Biological: Pneumococcal conjugate vaccineInfants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine

Who may qualify

Ages: 6 weeks to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

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
Vi-CRM197 vaccine	Biological	Vi-CRM, Adults, Vi-CRM, Children, Vi-CRM, Infants, Vi-CRM, Older infants
Vi Polysaccharide (PS) vaccineAlso: Typherix	Biological	Vi-PS, Adults, Vi-PS, Children
Pneumococcal conjugate vaccineAlso: Prevenar 13	Biological	PNC13, Infants, PNC13, Older infants, Vi-PS, Children

Primary outcome

Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer
Time frame: At 28 days after last vaccination as compared to baseline
Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer
Time frame: At 6 months after last vaccination as compared to baseline
Anti-Vi ELISA Geometric Mean Concentration (GMC)
Time frame: At 28 days after last vaccination
Anti-Vi ELISA GMC
Time frame: At 6 months after last vaccination

1 secondary outcome

Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination
Time frame: During the 7-day follow-up period after vaccination

Results and safety

Results posted to the registry on 10 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vi-CRM, Adults	40	40
Vi-PS, Adults	40	37
Vi-CRM, Children	20	20
Vi-PS, Children	20	19
Vi-CRM, Older Infants	20	18
PNC13, Older Infants	20	18
Vi-CRM, Infants	20	20
PNC13, Infants	20	17

Primary outcome: Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer

Time frame: At 28 days after last vaccination as compared to baseline. Number (95% Confidence Interval). Unit: percentage of subjects

Measure	Vi-CRM, Adults n = 40	Vi-PS, Adults n = 40	Vi-CRM, Children n = 19	Vi-PS, Children n = 19	Vi-CRM, Older Infants n = 20	PNC13, Older Infants n = 17	Vi-CRM, Infants n = 20	PNC13, Infants n = 17
Value	100 (91 to 100)	85 (70 to 94)	100 (82 to 100)	89 (67 to 99)	95 (75 to 100)	0 (0 to 20)	85 (62 to 97)	6 (0 to 29)

Population analysed: Intention-to-treat analysis set, which included all participants who received the vaccination, those in whom at least one post-vaccination blood sample was collected, and those for whom at least one ELISA result was available.

Primary outcome: Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer

Time frame: At 6 months after last vaccination as compared to baseline. Number (95% Confidence Interval). Unit: percentage of subjects

Measure	Vi-CRM, Adults n = 40	Vi-PS, Adults n = 37	Vi-CRM, Children n = 20	Vi-PS, Children n = 19	Vi-CRM, Older Infants n = 18	PNC13, Older Infants n = 18	Vi-CRM, Infants n = 20	PNC13, Infants n = 17
Value	90 (76 to 97)	81 (65 to 92)	95 (75 to 100)	68 (43 to 87)	89 (65 to 99)	6 (0 to 27)	25 (9 to 49)	0 (0 to 20)

Population analysed: Intention-to-treat analysis set

Primary outcome: Anti-Vi ELISA Geometric Mean Concentration (GMC)

Time frame: At 28 days after last vaccination. Geometric mean (95% Confidence Interval). Unit: ELISA Units/mL

Measure	Vi-CRM, Adults n = 40	Vi-PS, Adults n = 40	Vi-CRM, Children n = 19	Vi-PS, Children n = 19	Vi-CRM, Older Infants n = 20	PNC13, Older Infants n = 17	Vi-CRM, Infants n = 20	PNC13, Infants n = 17
Value	153 (105 to 224)	44 (30 to 65)	136 (91 to 202)	53 (36 to 79)	109 (80 to 148)	1.43 (1.03 to 2)	23 (17 to 32)	2.33 (1.63 to 3.32)

Population analysed: Intention-to-treat analysis set

Primary outcome: Anti-Vi ELISA GMC

Time frame: At 6 months after last vaccination. Geometric mean (95% Confidence Interval). Unit: ELISA Units/mL

Measure	Vi-CRM, Adults n = 40	Vi-PS, Adults n = 37	Vi-CRM, Children n = 20	Vi-PS, Children n = 19	Vi-CRM, Older Infants n = 18	PNC13, Older Infants n = 18	Vi-CRM, Infants n = 20	PNC13, Infants n = 17
Value	59 (40 to 87)	36 (24 to 53)	23 (15 to 34)	25 (17 to 38)	22 (14 to 33)	3.12 (2.08 to 4.68)	3.76 (2.77 to 5.08)	1.41 (1.02 to 1.96)

Population analysed: Intention-to-treat analysis set

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Solicited Adverse Events (AEs) were collected during 7-day follow period after each vaccination. Serious AEs were collected throughout the study period. Unsolicited AEs were collected collected during 28-day follow period after each vaccination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vi-CRM, Adults	0 of 40 (0%)	24 of 40 (60%)	Not reported
Vi-PS, Adults	0 of 40 (0%)	29 of 40 (72.5%)	Not reported
Vi-CRM, Children	2 of 20 (10%)	19 of 20 (95%)	Not reported
Vi-PS, Children	1 of 20 (5%)	17 of 20 (85%)	Not reported
Vi-CRM, Older Infants	4 of 20 (20%)	18 of 20 (90%)	Not reported
PNC13, Older Infants	5 of 20 (25%)	20 of 20 (100%)	Not reported
Vi-CRM, Infants	5 of 20 (25%)	20 of 20 (100%)	Not reported
PNC13, Infants	3 of 19 (15.8%)	19 of 19 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 24290843Bhutta ZA, Capeding MR, Bavdekar A, Marchetti E, Ariff S, Soofi SB, Anemona A, Habib MA, Alberto E, Juvekar S, Khan RM, Marhaba R, Ali N, Malubay N, Kawade A, Saul A, Martin LB, Podda A. Immunogenicity and safety of the Vi-CRM197 conjugate vaccine against typhoid fever in adults, children, and infants in south and southeast Asia: results from two randomised, observer-blind, age de-escalation, phase 2 trials. Lancet Infect Dis. 2014 Feb;14(2):119-29. doi: 10.1016/S1473-3099(13)70241-X. Epub 2013 Nov 28.

Related trials for Typhoid Fever

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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.

NVGH study director

Novartis

2 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vi-CRM197 vaccine, Vi Polysaccharide (PS) vaccine and Pneumococcal conjugate vaccine in people with Typhoid Fever, run by Novartis at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: finished, as of the sponsor's last update on 1 May 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in India, Pakistan. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer (time frame: At 28 days after last vaccination as compared to baseline). The study lists 4 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 NCT01229176, 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 1 May 2014.