Active Ingredient vaccine
EARLY PHASE CLINICAL DEVELOPMENT PLAN
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TABLE OF CONTENTS
Table of contents
2
Abbreviations
3
1.
BACKGROUND AND RATIONALE
5
1.1.
Epidemiology and medical environment
5
1.2.
Targets of the vaccine
5
1.3.
Status of competition
5
1.4.
Scientific Rationale for vaccine development
5
2.
MEDICAL STRATEGY
7
2.1.
Strategy for phase I/IIa
7
2.2.
Foreseen strategy for further clinical development
7
3.
OUTLINE OF MAIN PIVOTAL CLINICAL TRIALS §
8
4.
ANALYTIC DEVELOPMENT PLAN
8
4.1.
Safety and reactogenicity
8
4.2.
Immunogenicity
9
4.3.
.4.4. Efficacy and effectiveness
9
5.
CLINICAL DEVELOPMENT FLOW-CHART
10
6.
SUMMARY OF PIVOTAL STUDIES
10
7.
LIST OF EXPERTS IN THE FIELD
11
8.
BIBLIOGRAPHY
12
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ABBREVIATIONS
CDP
cGMP
CT
CTA
CTP
Clinical Development Plan
Current Good Manufacturing Practice
Clinical Trial
Clinical Trial Application
Clinical Trial Protocol
DSMB
ELISA
Data Safety Monitoring Board
Enzyme-Linked ImmunoSorbent Assay
EPI
EVI
GIA
Expanded Programme of Immunization
European Vaccine Initiative
Growth Inhibition Assay
GMP
Good Manufacturing Practice
IB
ICH
Investigator Brochure
International Conference on Harmonisation
SAC
Scientific Advisory Committee
WHO
World Health Organization
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GENERAL INFORMATION
MISSION
To be validated with Scientists and Investigators.
Clearly state what are the intended aims of the product in terms of targets (age, countries, risk groups...), expected
performances of the vaccine and the major criteria for a Go / No Go decision
PRODUCT CHARACTERISTICS
Antigens, adjuvants, route of administration
EVI PROJECT TEAM
Project Team Leader/Coordinator:
Medical
Production
Medical Expert:
Clinical Monitor:
Statistics/Epidemiol
ogy responsible:
Principal Biological
Evaluator:
Data manager:
Product Manager
Inventor:
Pharmacotoxicology
responsible:
Stability studies
responsible:
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1.
BACKGROUND AND RATIONALE
(maximum 10 pages)
1.1.
Epidemiology and medical environment
known and unknown
which information is lacking?
are epidemiological studies needed for the development of the vaccine?
What is (are ) the correlate(s) of protection or immunity in target populations?
Are certain immune responses correlated with better clinical outcome?
Are there genetic (haplotype) differences in populations that do better that others (immunologically and clinically)?
1.2.
Targets of the vaccine
age, geographical zones, special risk groups, expected performance of the vaccine
1.3.
Status of competition
Current vaccines and other products available (justification of this development)
1.4.
Scientific Rationale for vaccine development
1.4.1.
Antigen choice
( stage specific or multi stage, single or multiple antigens)
Stage specific----simple but lower chance of success ?
Multi stage---------complex but greater chance of success?
Do humans naturally respond to this antigen ?
What are the theoretical reasons why an immune response to this antigen would be detrimental to the
parasite.
Are there in-vivo or in vitro tests that support this?
What would the investigators consider the best proof of concept test that they could design?
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1.4.2.
The choice of vector/formulation/antigen presentation system
Do we know what type of immune response we wish to induce?
Is an antigen delivery system known that achieves the required response?
Is this system validated (in animals? in man?) as a viable option for wide-spread use?
1.4.3.
Potential advantages and limitations
1.4.4.
Preclinical development
Correlates of protection/development of immunological tests for assessment of the quality of the immune response
Animal models
1.4.5.
Route of administration
Is there any data to support alternative routes of administration of interest for the antigen (IM, SC, ID, oral etc
…)
1.4.6.
Summary of clinical development to date
Results of previous studies.
1.4.7.
Vaccine production
How will the vaccine be produced ?
(Recombinant protein/synthetic peptide/live vector/DNA vaccine)
What expression system is required (prokaryotic,eukaryotic etc)
Is an adjuvant required
What reagents do we need to make to control our product and its immunogenicity
What assays do we need to develop, qualify and/or validate before we initiate clinical trials
Animal studies, including pharmacotoxicological studies
Stability studies
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Quality control studies : are the test already developed and is there any product characteristics already available ?
2.
MEDICAL STRATEGY
This important section should describe carefully the intended clinical development strategy which will result in a
clear decision to proceed to development with a well defined product and with reasonable probability of success.
2.1.
Strategy for phase I/IIa
Define the rationale for the phase I-IIa studies. If there is a pivotal study which would form the basis of a
Go/No Go decision define the hypothesis, objectives, main outcome measurements, study design, time lines and
clinical costs
2.2.
Foreseen strategy for further clinical development
Underline the main critical steps of future development with a special emphasise to critical issues that may make
the development of special difficulty.
How do you plan to prove efficacy or to bridge to a surrogate marker?
Comment on sample size for efficacy trials, on possible study sites, on the need for more epidemiological data.
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3.
OUTLINE OF MAIN PIVOTAL CLINICAL TRIALS §
Trial
Phase
#
Site
Objectives
(country)
# of
Duration
Budget
subjects
(months)
estimate (€)
Grand
0
Total
§ as an example may include two or more of the following:
1: consistency study
2. interaction with other vaccine
3. efficacy study
4. large scale safety study
5. safety and immunogenicity in special populations
4.
ANALYTIC DEVELOPMENT PLAN
The analytical development plan must be completed for the phase I/IIa studies. If possible, complete as much as
can be projected for the rest of the phases to licensure. (Those studies, especially the efficacy study(ies), will be
completed in detail for the Full Clinical Development Plan).
4.1.
Safety and reactogenicity
4.1.1.
Safety
(documentation on the incidence of rare, serious unexpected adverse reactions)
Total number of adults ( > 15 years)
Total number of children (2 to 15 years old)
Total number of infants (0 to 2 years; can be more precise)
0
Grand total
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4.1.2.
Reactogenicity
indicate in this table all studies that will contribute to the documentation of reactogenicity (systemic and local usual
adverse reactions)
Study #
Site
Objectives and Design
# of subjects
Grand Total
4.2.
0
Immunogenicity
4.2.1.
Justification of final formulation
(This table should indicate phase I and II, dose response, and adjuvant studies that will contribute to the final
formulation)
Study #
Site
Objectives and Design
# of
Assay(s) to be used
subjects
Total
0
4.2.2.
Other clinical research studies
specific immunogenicity studies (such as ADCI, CMI, ... etc) and other studies that will contribute to a
Go/No Go decision
Study #
Site
Total
4.3.
# of sujects
objective and design
0
Efficacy and effectiveness
indicate here what information on efficacy might be obtained during early clinical research phases ( such as challenge
studies or natural exposure
Study #
Site
Design
# of sbjects
End point
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Study #
Site
Design
# of sbjects
Total
5.
End point
0
CLINICAL DEVELOPMENT FLOW-CHART
This flow diagram (decision tree) should indicate:

Pivotal studies

Go / no Go decisions
 Links between studies
It should cover all clinical development through licensure
As many points may be still uncertain you can group several studies under a single heading (for example: studies
dose ranging, schedule of immunisation, interactions may be summarized under a single " phase II optimisation
studies" heading
6.
SUMMARY OF PIVOTAL STUDIES
The title and the trial number of each pivotal study must be stated below. The trial synopsis will have to be
attached as appendix.
( the number of lines for each topic is not limited: the summary should contain enough information to allow writting
the full protocol)
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7.
LIST OF EXPERTS IN THE FIELD
For each expert please indicate:
Name
Institution
Adress
Field of expertise (such as
epidemiology, case definition,
immunogenicity, study design ...etc)
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8.
BIBLIOGRAPHY
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