Pertussis Clinical Trial
Official title:
A Phase II Randomized, Observer-blind Controlled Pilot Study to Compare the Safety and Immunogenicity of Acellular Pertussis Vaccines Including Chemically or Genetically-detoxified Pertussis Toxin in Adolescents Aged 11-15 Years Previously Immunized With Acellular Pertussis Vaccines
This is a phase II, randomized double-center, and observer-blind controlled pilot vaccine
trial in 11 to 15 years old healthy subjects to assess the immunogenicity of the genetically
detoxified pertussis toxin (rPT) included in a novel acellular pertussis vaccine (Pertagen®)
manufactured by BioNet-Asia when delivered by the intramuscular route to adolescents
previously primed and boosted with chemically-detoxified PT, along with Td-pur® and in
comparison with that of Boostrix® dTpa.
At Day 0, eligible volunteers will undergo a venous bleed for the determination of baseline
values and enter the randomization scheme, being allocated to one of two groups: A
(Pertagen® + Td-pur®), B (Boostrix® dTpa).
Randomized participants will receive one dose of Pertagen® and Td-pur® (Group A) or 1 dose
of Boostrix® dTpa (Group B) by intramuscular injection in the deltoid. All subjects will be
observed in the Plateforme de Recherché Pédiatrique for 30 minutes after immunization.
Post-immunization local and systemic reactions will be followed up for 7 days after
immunization. Adverse events will be followed for 28 days after immunization.
At Day 28, a second visit (study end visit) will take place for safety evaluation and blood
draw for immunogenicity evaluation.
Blood draws performed on Day 0 (Baseline) and Day 28 will be used to evaluate immune
response to study vaccines.
The primary statistical analysis will be performed with visit 2 (Day 28) data to compare the
immunogenicity and safety of one dose of Pertagen®, given simultaneously with Td-pur®, to
those elicited by Boostrix® dTpa.
A significant increase of pertussis incidence is reported in a growing number of countries.
This resurgence is considered as resulting from the limited durability of aP-vaccine-induced
immunity and is associated with increased mortality in young infants and morbidity at all
age groups. As the pertussis immunity acquired through immunization or infection is
short-lived, its maintenance or reactivation requires repeat boosting at regular time
points. Thus, novel strategies capable of reactivating pertussis immunity in older children,
adolescents or adults, including pregnant women, are needed.
A puzzling observation is that the efficacy of current acellular pertussis vaccines (which
contain chemically-detoxified pertussis toxoid (PT)) is higher in infants and children than
adolescents, in whom vaccine efficacy is limited and rapidly wanes. This may derive - at
least in part - from priming and repeat immunizations with acellular vaccines containing
chemically-detoxified PT and thus induction of antibodies specific of the
chemically-detoxified PT but unable to efficiently recognize the native PT expressed by B.
pertussis.
The development of optimized acellular pertussis vaccines should thus include antigens with
a similar immunogenicity profile as native PT but deprived of its toxic properties. This is
best achieved through the genetic rather than chemical detoxification of PT, which results
in both nontoxic and immunogenic PT.
Clinical studies have shown the good tolerability profile and the superior immunogenicity
profile of acellular pertussis vaccines including genetically-detoxified PT (rPT) in adults
and adolescents previously primed with whole-cell pertussis (wP) vaccines. As whole-cell
vaccines express native PT, whether the superior immunogenicity of rPT will be observed in
adolescents/adults previously primed with acellular pertussis vaccines containing
chemically-detoxified PT is of key importance.
This is a phase II randomized, observer-blind controlled study to compare the safety and
immunogenicity of acellular pertussis vaccines including chemically or
genetically-detoxified pertussis toxin in adolescents aged 11-15 years. The primary
objective is to assess the immunogenicity of the genetically detoxified pertussis toxin
(rPT) included in a novel acellular pertussis vaccine (Pertagen®) when delivered by the
intramuscular route to adolescents previously primed and boosted with chemically-detoxified
PT, along with Td-pur® and in comparison with that of Boostrix® dTpa. The secondary
objectives are (1) to assess safety of Pertagen® when administered with Td-pur® to
adolescents as compared to Boostrix® dTpa and (2) to assess the humoral responses elicited
by Pertagen® when administered with Td-pur® as compared to Boostrix® dTpa.
In this study, exploratory immunological measures will also be performed (pending sufficient
or additional funding). These are anticipated to include:
- The assessment of antibody titers to specific neutralizing and non-neutralizing
epitopes of PT, by competitive ELISA, before and after (Day 28) boosting with Pertagen®
and Boostrix® dTpa.
- To assess cellular responses to PT before and after boosting with Pertagen® and
Boostrix® dTpa.
- To assess the frequency and phenotype of PT-specific memory B cell responses (as
compared to tetanus toxoid) before and after boosting with Pertagen® or Boostrix® dTpa
(i.e. at Day 0 and Day 28).
- To characterize changes in cellular responses following boosting with Pertagen® or
Boostrix® dTpa
Three vaccines will be used in the study. The BioNet-Asia study vaccine (Pertagen®), Td-pur®
(Novartis/GSK) which will be concomitantly administered with the study vaccine, and the
control Boostrix® dTpa.
The investigational product Pertagen® will be manufactured, labeled, packaged and released
for clinical use by BioNet-Asia, in accordance with the requirements of Good Manufacturing
Practices.Both Td-pur® and Boostrix® dTpa vaccines used in this study are commercially
available in Switzerland and will be purchased for the study. One batch of each vaccine will
be used for the entire study.
All vaccines are presented in 0.5 mL pre-filled syringes to be administered by intramuscular
injection. The study vaccine Pertagen® and Boostrix® dTpa will be administered in the
non-dominant deltoid. If applicable, Td-pur® will be administered in the contralateral
deltoid.
At Day 0, eligible subjects will be randomized in a 1:1 ratio into one of the following
vaccine groups:
Group 1 Pertagen® and Td-pur 30 volunteers Group 2 Boostrix® dTpa 30 volunteers
A randomization list containing subject numbers and vaccine group assignments will be
established and provided to the clinical investigators. Each participant will be immunized
according to the vaccine group assignment. At study site, the Principal investigator will
designate the blinded and unblinded teams in order to keep the observer-blind design of the
study.
The unblinded personal will be responsible for study vaccine preparation, handling, storage
and accountability, and immunization.
The blinded team will be responsible for assessing adverse events. The laboratory staff
performing the immunological assays will also be blinded. After vaccination, volunteers will
be observed for 30 minutes at study site for any immediate post-immunization reactions.
Reactogenicity and safety will be assessed during study visits at the clinical trial unit
(CTU) on Day 0 and Day 28 after immunization. At Day 0 (Visit 1, vaccination day), a Diary
Card will be distributed to study volunteer to record post-immunization local and systemic
reactions and adverse events. At Day 28 (Visit 2), investigator will reconcile and
transcribe the Diary Card information in the CRF. Post-immunization local and systemic
reactions will be collected and monitored for 7 days after vaccination. All adverse events,
including SAEs, will be collected and monitored for 28 days after vaccination (until Visit
2).
Study participants will be contacted by phone at Day 7 to confirm that adverse reactions
have subsided. Should this not be the case, an unscheduled visit will be considered as
appropriate.
All AEs and SAEs occurring within the 28 days following treatment and observed by the
Investigator or reported by the volunteer, whether or not attributed to study intervention,
will be recorded in the CRF. All AEs that result in a volunteer's withdrawal from the study
will be followed up until a satisfactory resolution occurs, or until a non-study related
causality is assigned (if the volunteer consents to this).
Sample size calculation This is a phase II randomized, observer-blind controlled pilot study
to compare the safety and immunogenicity of acellular pertussis vaccines including
chemically or genetically-detoxified pertussis toxin in adolescents previously immunized
with acellular vaccines. The sample size for this study is based on clinical and practical
considerations and not on a formal statistical power calculation. Where applicable, 2-sided
test at the 5% significance level will be utilized with no multiplicity adjustment. P-values
will be considered exploratory only. Sixty volunteers will be randomized in total, with 30
in each group.
Safety analysis The safety analysis will include all randomized subjects who have received a
dose of study vaccine.
The overall percentage of subjects with at least one spontaneously reported adverse event,
with date of onset up to 28 days after vaccination will be tabulated with exact 95%
confidence intervals, by type of adverse event; by severity; and by causality. They will be
displayed by vaccine group as both frequencies and percentages on the ITT data set.
All reported adverse events that start post-vaccination will be tabulated. If a given
disease is already reported as ongoing at the first visit on the medical history pages, it
will be counted and tabulated as a vaccine emergent adverse event only if it worsens after
the immunization with the study vaccine.
Serious adverse events and discontinuation due to adverse event(s) will be described in
detail by vaccine group.
Immunogenicity analyses The primary immunogenicity endpoint will assess the immune response
to Pertagen® - as compared to Boostrix® dTpa - by measuring the Day 28 geometric mean
concentration (GMC) of neutralizing antibodies to PT.
The other immunogenicity end-points include:
- GMCs of PT, FHA, tetanus and diphtheria-toxoid specific IgG antibodies measured by
ELISA
- Seroresponse rates of PT, FHA, tetanus and diphtheria-toxoid specific IgG antibodies
measured by ELISA
- Reverse cumulative distribution curves of PT neutralizing antibodies, and of PT, FHA,
tetanus and diphtheria-toxoid IgG antibodies
- To compare PT-specific responses elicited by Pertagen® in adolescents previously
immunized (this study) or not (BioNet Phase II/III TDA202) by acellular pertussis
vaccines The following descriptive statistics will be provided for each variable:
number of subjects, percentages, mean, geometric mean, standard deviation, median,
minimum, maximum, and range.
Quality Control and Quality Assurance Procedure Approved site-specific SOPs will be used at
clinical and laboratory sites. Monitoring will be performed according to ICH Good Clinical
Practice (GCP) by the Centre de Recherche Clinique (CRC) of the University Hospital of
Geneva. Following a Monitoring Plan and written SOPs, the monitors will verify that the
clinical trial is conducted and data are generated, documented and reported in compliance
with the protocol, GCP and the applicable regulatory requirements. The CTU will provide
direct access to all trial-related source data, documents and reports for the purpose of
monitoring and inspection by local and regulatory authorities.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Not yet recruiting |
NCT04056728 -
A Phase IV Study to Assess the Safety of EupentaTM Inj
|
Phase 4 | |
Completed |
NCT02453048 -
Study of BPZE1 (High Dose) Nasal Live Attenuated B. Pertussis Vaccine
|
Phase 1 | |
Completed |
NCT02526394 -
Pertussis and Meningitis C Concomitant Vaccination in Adolescents
|
Phase 4 | |
Completed |
NCT01917357 -
A Comparison of the Immunogenicity and Safety of Quinvaxem in Mono-dose Vials and Uniject
|
Phase 3 | |
Completed |
NCT01689324 -
Study of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine (ADACEL®) as a Booster in Adolescents
|
Phase 1/Phase 2 | |
Completed |
NCT01214889 -
Study of PENTAXIM™ Vaccine Versus TETRAXIM™ Vaccine Given With ACTHIB™ Vaccine in South Korean Infants.
|
Phase 3 | |
Completed |
NCT00804284 -
Database Surveillance Safety Study of PENTACEL® Vaccine
|
N/A | |
Completed |
NCT00514709 -
Immunogenicity Study of Antibody Persistence and Booster Effect of DTaP-HB PRP~T Combined Vaccine in Filipino Infants
|
Phase 3 | |
Completed |
NCT00534833 -
Immunogenicity Study of Antibody Persistence and Booster Effect of DTaP-HB-PRP~T Combined Vaccine or Tritanrix-HepB/Hib™
|
Phase 3 | |
Completed |
NCT00524732 -
Assessment of the Reactogenicity of ADACEL® (TdcP Vaccine) in Children and Adolescents 7 to 19 Years of Age
|
N/A | |
Completed |
NCT00772369 -
Retrospective Survey of Safety of Fourth Dose Pentacel® in Children
|
Phase 4 | |
Completed |
NCT01457495 -
Immunogenicity and Safety of DTPa-HBV-IPV/Hib Compared to DTPa-IPV/Hib and HBV Administered Concomitantly
|
Phase 2 | |
Completed |
NCT01267058 -
Booster Study of Combined Diphtheria-tetanus-acellular Pertussis Vaccine in Healthy Adults
|
Phase 3 | |
Completed |
NCT00004800 -
Phase III Randomized, Double-Blind, Placebo-Controlled Study of Acellular and Whole-Cell Pertussis Vaccines
|
Phase 3 | |
Completed |
NCT02858440 -
A Study to Assess the Immunogenicity and Safety of GSK Biologicals' Infanrix-IPV/Hib Vaccine Administered as a Three-dose Vaccination Course at 3, 4.5 and 6 Months of Age and a Booster Dose at 18 Months of Age in Healthy Infants in Russia
|
Phase 3 | |
Recruiting |
NCT04023929 -
Sources of COmplement in Meningococcal and Pertussis Serum Bactericidal Antibody Assays
|
||
Completed |
NCT03541499 -
Safety and Immunogenicity of Intranasal BPZE1 Vaccination in Healthy Adults
|
Phase 2 | |
Completed |
NCT02587520 -
Study of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine Adsorbed in Healthy Subjects
|
Phase 1/Phase 2 | |
Completed |
NCT04589312 -
Maternal Pertussis Wholecell Responses
|
Phase 2 | |
Completed |
NCT02274285 -
DTaP-IPV/Hib Vaccine Primary & Booster Vaccinations Versus Co-administration of DTaP-IPV and Hib Vaccine in Japanese Infants
|
Phase 3 |