Streptococcal InfectionsPhase 2NCT01412801

Magnitude of the Antibody Response to and Safety of a GBS Trivalent Vaccine in HIV Positive and HIV Negative Pregnant Women and Their Offsprings

A Phase 2 study testing Group B streptococcus vaccine in people with Streptococcal Infections and Gram-Positive Bacterial Infections, run by Novartis Vaccines 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

The study compared the magnitude of the antibody response and safety of a GBS Trivalent Vaccine in HIV positive and HIV negative pregnant women and their offspring. In addition the study investigated the maternal to fetal transfer of antibodies induced by the investigational vaccine. Read more about this study

Who is it for?: Ages 18 to 40 years, women only
Conditions the study is for: Streptococcal Infections, Gram-Positive Bacterial Infections, Bacterial Infections
What is being tested?: Group B streptococcus vaccine
Type of treatment: Vaccines
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 270 participants
Where: 2 sitesin 2 countries
Study dates: Sep 2011to Dec 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 18 to 40 years
Women only
No healthy volunteers
Adult

Who may be able to join

Pregnant women 18-40 years of age between 24-35 weeks gestation
Women who were HIVneg or HIVpos with WHO stage I or II disease and with CD4+ counts > 50 cells/µL

Who cannot join

Women who had CD4+ count ≤ 50 cells/µL
Women who were HIVpos with WHO stage III or IV disease, history of severe allergic reactions after previous vaccinations

Trial locations and contacts

2 sites in 2 countries.

Country

City, postcode or hospital

2 sites in 2 countries

Malawi1 site

Limbe Health Center
Blantyre

Other trials in Malawi

South Africa1 site

Chris Hani Baragwanath Hospital
Bertsham, 2013

Other trials in South Africa

About this study

Official title: A Phase II Open-Label, Multi-Center Study of a Group B Streptococcus Vaccine in HIV Positive and HIV Negative Pregnant Women

Conditions: Streptococcal Infections, Gram-Positive Bacterial Infections, Bacterial Infections
Being tested: Group B streptococcus vaccine
Keywords: Group B streptococcus, GBS, Vaccine, Prevention of group B streptococcus infection
Medical subject headings: Streptococcal Infections, Gram-Positive Bacterial Infections, Bacterial Infections

What participants receive

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

Group B streptococcus vaccineBiological
Subjects receive one dose of 5 μg of each of the 3 glycoconjugates present in the Group B streptococcus vaccine.

Study groups in NCT01412801
Study group	Role	What they receive
HIVneg	Experimental	HIV-antibody negative maternal subjects at 24 to 35 weeks gestation received one dose of Group B streptococcus vaccine. Receives: Biological: Group B streptococcus vaccine
HIVposCD4HIGH	Experimental	HIV-antibody positive maternal subjects at 24 to 35 weeks gestation with CD4+ count >350 cells/µL received one dose of Group B streptococcus vaccine. Receives: Biological: Group B streptococcus vaccine
HIVposCD4LOW	Experimental	HIV-antibody positive maternal subjects at 24 to 35 weeks gestation with CD4+ count ≤350 cells/µL but > 50 cells/µL received one dose of Group B streptococcus vaccine Receives: Biological: Group B streptococcus vaccine

What is being measured

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

Geometric Mean Concentrations (GMCs) of Antibodies in Maternal Subjects and Infants at Delivery/Birth
GMCs of Group B Streptococcus (GBS)-specific Abs against serotypes Ia, Ib and III in mothers and in infants at delivery/birth are presented.
Measured: Day of delivery/birth
Geometric Mean Antibody Transfer Ratio Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL), for GBS Serotypes Ia, Ib and III at Delivery/Birth.
The Geometric mean transfer ratio of GBS-specific Ab against serotypes Ia, Ib and III at delivery is calculated as the geometric mean of the pairwise ratios between the antibody concentrations from infant at birth and to maternal serum concentration at delivery.
Measured: Day of delivery/birth

Secondary outcomes (6)

Vaccine Induced Maternal Serotype Specific GBS Antibody Levels for GBS Serotypes Ia, Ib and III at Day 1, 15, 31 and at Delivery
Immunogenicity was measured as Geometric Mean Concentration of Antibody levels for GBS Serotypes Ia, Ib and III after receiving one dose of GBS Trivalent Vaccine.
Measured: Day 1, 15, 31 and at Delivery
Percentages of Maternal Subjects With The Enzyme-linked Immunosorbent Assay (ELISA) Antibody Levels for GBS Serotypes Ia, Ib and III Above a Specific Threshold at Delivery
Immunogenicity was measured in terms of the percentages of maternal subjects with ELISA Antibody Levels for GBS Serotypes Ia, Ib and III Above a Specific Threshold after receiving one dose of GBS Trivalent Vaccine.Threshold values of 0.1, 0.2, 0.5, 1, 2, 3, 5, and 8 μg/mL were used for serum concentrations for maternal subjects.
Measured: Day of Delivery
Percentages of Subjects With Solicited Local Adverse Events (AEs)
Safety was assessed in terms of the number of subjects with solicited local AEs after receiving one dose of the GBS Trivalent Vaccine
Measured: From 6 Hours to Day 7 After Each Vaccination, for up to 24 weeks
Percentages of Subjects With Solicited Systemic AEs
Safety was assessed in terms of the number of subjects with solicited systemic AEs after receiving one dose of the GBS Trivalent Vaccine
Measured: From 6 Hours to Day 7 After Each Vaccination, for up to 24 weeks
Percentages of Subjects Who Experienced Unsolicited Adverse Events
Safety was assessed in terms of the number of subjects who experienced Unsolicited Adverse Events after receiving one dose of the GBS Trivalent Vaccine
Measured: Day 1 to Study Termination, for up to 24 weeks
Percentages of Infants Who Experienced Unsolicited Adverse Events
Safety in Infants was assessed in terms of the number of subjects who experienced Unsolicited Adverse Events since birth to study termination
Measured: Birth to Study Termination, for up to 24 weeks

Timeline

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

Sep 2011Dec 2012

First posted9 Aug 2011 (estimated)
Study startSep 2011
Primary completionOct 2012
Study completionDec 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 Streptococcal InfectionsStudies 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 270 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01412801
Sponsor's protocol ID: V98_05
Status last verified: Sep 2014
First submitted: 8 Aug 2011
Last updated: 12 Sep 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, Mboizi R, Koen A, Jose L, Olugbosi M, Wittke F, Slobod K, Dull PM. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis. 2016 May;16(5):546-555. doi: 10.1016/S1473-3099(15)00484-3. Epub 2016 Feb 8.
PubMed 26869376

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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All Streptococcal Infections trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Open-Label, Multi-Center Study of a Group B Streptococcus Vaccine in HIV Positive and HIV Negative Pregnant Women
ClinicalTrials.gov ID: NCT01412801
Acronym / sponsor ID: V98_05
Conditions: Streptococcal Infections, Gram-Positive Bacterial Infections, Bacterial Infections
Keywords: Group B streptococcus, GBS, Vaccine, Prevention of group B streptococcus infection
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 270 participants (actual)
Lead sponsor: Novartis VaccinesIndustry (pharma, biotech, devices)
Study start: Sep 2011
Primary completion: Oct 2012 (actual)
Study completion: Dec 2012 (actual)
First posted: 9 Aug 2011 (estimated)
Results: Posted 12 Sep 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: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
HIVneg	Experimental	Biological: Group B streptococcus vaccineHIV-antibody negative maternal subjects at 24 to 35 weeks gestation received one dose of Group B streptococcus vaccine.
HIVposCD4HIGH	Experimental	Biological: Group B streptococcus vaccineHIV-antibody positive maternal subjects at 24 to 35 weeks gestation with CD4+ count >350 cells/µL received one dose of Group B streptococcus vaccine.
HIVposCD4LOW	Experimental	Biological: Group B streptococcus vaccineHIV-antibody positive maternal subjects at 24 to 35 weeks gestation with CD4+ count ≤350 cells/µL but > 50 cells/µL received one dose of Group B streptococcus vaccine

Who may qualify

Ages: 18 to 40 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (2 listed)

Pregnant women 18-40 years of age between 24-35 weeks gestation
Women who were HIVneg or HIVpos with WHO stage I or II disease and with CD4+ counts > 50 cells/µL

Key exclusion criteria (2 listed)

Women who had CD4+ count ≤ 50 cells/µL
Women who were HIVpos with WHO stage III or IV disease, history of severe allergic reactions after previous vaccinations

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
Group B streptococcus vaccineSubjects receive one dose of 5 μg of each of the 3 glycoconjugates present in the Group B streptococcus vaccine.	Biological	HIVneg, HIVposCD4HIGH, HIVposCD4LOW

Primary outcome

Geometric Mean Concentrations (GMCs) of Antibodies in Maternal Subjects and Infants at Delivery/Birth
Time frame: Day of delivery/birth
GMCs of Group B Streptococcus (GBS)-specific Abs against serotypes Ia, Ib and III in mothers and in infants at delivery/birth are presented.
Geometric Mean Antibody Transfer Ratio Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL), for GBS Serotypes Ia, Ib and III at Delivery/Birth.
Time frame: Day of delivery/birth
The Geometric mean transfer ratio of GBS-specific Ab against serotypes Ia, Ib and III at delivery is calculated as the geometric mean of the pairwise ratios between the antibody concentrations from infant at birth and to maternal serum concentration at delivery.

6 secondary outcomes

Vaccine Induced Maternal Serotype Specific GBS Antibody Levels for GBS Serotypes Ia, Ib and III at Day 1, 15, 31 and at Delivery
Time frame: Day 1, 15, 31 and at Delivery
Percentages of Maternal Subjects With The Enzyme-linked Immunosorbent Assay (ELISA) Antibody Levels for GBS Serotypes Ia, Ib and III Above a Specific Threshold at Delivery
Time frame: Day of Delivery
Percentages of Subjects With Solicited Local Adverse Events (AEs)
Time frame: From 6 Hours to Day 7 After Each Vaccination, for up to 24 weeks
Percentages of Subjects With Solicited Systemic AEs
Time frame: From 6 Hours to Day 7 After Each Vaccination, for up to 24 weeks
Percentages of Subjects Who Experienced Unsolicited Adverse Events
Time frame: Day 1 to Study Termination, for up to 24 weeks
Percentages of Infants Who Experienced Unsolicited Adverse Events
Time frame: Birth to Study Termination, for up to 24 weeks

Results and safety

Results posted to the registry on 12 Sep 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
HIVposCD4LOW_Maternal	91	87
HIVposCD4HIGH_Maternal	89	84
HIVneg_Maternal	90	83
HIVposCD4LOW(Infants)	91	87
HIVposCD4HIGH(Infants)	88	85
HIVneg(Infants)	87	84

Primary outcome: Geometric Mean Concentrations (GMCs) of Antibodies in Maternal Subjects and Infants at Delivery/Birth

Time frame: Day of delivery/birth. Geometric mean (95% Confidence Interval). Unit: μg/mL

Measure	HIVposCD4LOW_Maternal n = 83	HIVposCD4HIGH_Maternal n = 81	HIVneg_Maternal n = 83	HIVposCD4LOW(Infants) n = 83	HIVposCD4HIGH(Infants) n = 81	HIVneg(Infants) n = 83
GBS serotypes Ia (83, 81, 83, 79, 81, 83)	2.07 (1.44 to 2.98)	2.31 (1.6 to 3.34)	3.98 (2.75 to 5.74)	1.01 (0.66 to 1.56)	1.22 (0.8 to 1.87)	3.91 (2.56 to 5.96)
GBS serotypes Ib(74, 80, 82, 44, 56, 57)	1.84 (1.22 to 2.77)	2.4 (1.64 to 3.52)	4.08 (2.85 to 5.83)	1.31 (0.78 to 2.19)	1.62 (1.03 to 2.56)	2.67 (1.7 to 4.2)
GBS serotypes III (83, 72, 82, 54, 51, 66)	1.07 (0.71 to 1.6)	1.03 (0.69 to 1.53)	3.61 (2.51 to 5.18)	0.6 (0.36 to 0.99)	0.52 (0.31 to 0.88)	3.88 (2.47 to 6.1)

Population analysed: Full Analysis Set (FAS)-Maternal and Infant Subjects: Maternal subjects provided at least one evaluable serum sample result at delivery; infant subjects provided at least one evaluable sample result at birth (from cord blood, or peripheral blood within 72 hours when cord blood was unavailable).

Primary outcome: Geometric Mean Antibody Transfer Ratio Between Infant Antibody Level (μg/mL) and Maternal Antibody Level (μg/mL), for GBS Serotypes Ia, Ib and III at Delivery/Birth.

Time frame: Day of delivery/birth. Geometric mean (95% Confidence Interval). Unit: Ratios

Measure	HIVposCD4LOW n = 79	HIVposCD4HIGH n = 79	HIVneg n = 83
Serotype Ia	0.58 (0.49 to 0.69)	0.6 (0.51 to 0.72)	0.72 (0.61 to 0.85)
Serotype Ib (41,54,57)	0.51 (0.38 to 0.69)	0.64 (0.5 to 0.83)	0.49 (0.38 to 0.63)
Serotype III (53,44,66)	0.6 (0.44 to 0.82)	0.51 (0.36 to 0.72)	0.56 (0.43 to 0.75)

HIVposCD4LOW vs HIVposCD4HIGH: Vaccine Group Ratios (Serotype Ia): 0.96 (98.4% CI 0.71 to 1.3)
HIVposCD4LOW vs HIVneg: Vaccine Group ratios (Serotype Ia): 0.81 (98.4% CI 0.6 to 1.09)
HIVposCD4HIGH vs HIVneg: Vaccine Group ratios (Serotype Ia): 0.84 (98.4% CI 0.63 to 1.14)

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Throughout the study period, for up to 24 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
HIVposCD4LOW (Infants)	17 of 91 (18.7%)	13 of 91 (14.3%)	Not reported
HIVposCD4HIGH (Infants)	16 of 88 (18.2%)	11 of 88 (12.5%)	Not reported
HIVneg (Infants)	16 of 87 (18.4%)	7 of 87 (8%)	Not reported
Total (Infants)	49 of 266 (18.4%)	31 of 266 (11.7%)	Not reported
HIVposCD4LOW_Maternal Subjects	25 of 90 (27.8%)	55 of 90 (61.1%)	Not reported
HIVposCD4HIGH_Maternal Subjects	28 of 89 (31.5%)	68 of 89 (76.4%)	Not reported
HIVneg_Maternal Subjects	29 of 90 (32.2%)	71 of 90 (78.9%)	Not reported
Total Maternal Subjects	82 of 269 (30.5%)	194 of 269 (72.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26869376Heyderman RS, Madhi SA, French N, Cutland C, Ngwira B, Kayambo D, Mboizi R, Koen A, Jose L, Olugbosi M, Wittke F, Slobod K, Dull PM. Group B streptococcus vaccination in pregnant women with or without HIV in Africa: a non-randomised phase 2, open-label, multicentre trial. Lancet Infect Dis. 2016 May;16(5):546-555. doi: 10.1016/S1473-3099(15)00484-3. Epub 2016 Feb 8.

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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.

Novartis Vaccines study chair

Novartis Vaccines

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 Group B streptococcus vaccine in people with Streptococcal Infections and Gram-Positive Bacterial Infections, run by Novartis Vaccines 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?

The sponsor lists 2 inclusion and 2 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: finished, as of the sponsor's last update on 12 Sep 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 Malawi, South Africa. 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 12 Sep 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?

Geometric Mean Concentrations (GMCs) of Antibodies in Maternal Subjects and Infants at Delivery/Birth (time frame: Day of delivery/birth). 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 NCT01412801, 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 12 Sep 2014.