Clinical Trials Register

Summary
EudraCT Number:	2010-023873-20
Sponsor's Protocol Code Number:	B1971009(6108A1-3001)
National Competent Authority:	Finland - Fimea
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-09-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Finland - Fimea

A.2

EudraCT number

2010-023873-20

A.3

Full title of the trial

A PHASE 3, RANDOMIZED, ACTIVE-CONTROLLED, OBSERVER-BLINDED TRIAL TO ASSESS THE LOT CONSISTENCY, SAFETY, TOLERABILITY, AND IMMUNOGENICITY OF A MENINGOCOCCAL SEROGROUP B BIVALENT RLP2086 VACCINE IN HEALTHY SUBJECTS AGED ≥10 TO <19 YEARS

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical trial to determine if the investigational MnB vaccine works the same every time a batch (or lot) of the vaccine is made

A.4.1

Sponsor's protocol code number

B1971009(6108A1-3001)

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc, 235 East 42nd Street, New York, NY 10017
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Pfizer Inc, 235 East 42nd Street, New York, NY 10017
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Pfizer Inc
B.5.2	Functional name of contact point	Clinical Trials.gov Call Centre
B.5.3	Address:
B.5.3.1	Street Address	235 E 42nd Street
B.5.3.2	Town/ city	New York
B.5.3.3	Post code	NY 10017
B.5.3.4	Country	United States
B.5.4	Telephone number	+18007181021
B.5.5	Fax number	+13037391119
B.5.6	E-mail	ClinicalTrials.govCallCentre@pfizer.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	MnB rLP2086 Vaccine
D.3.2	Product code	MnB rLP2086 (PF-05212366)
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MnB rLP2086 Subfamily A
D.3.9.1	CAS number	N/a
D.3.9.2	Current sponsor code	N/a
D.3.9.3	Other descriptive name	N/a
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MnB rLP2086 Subfamily B
D.3.9.1	CAS number	N/a
D.3.9.2	Current sponsor code	N/a
D.3.9.3	Other descriptive name	N/a
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	120
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Sterile saline solution (0.9%)
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	n/a
D.3.9.1	CAS number	n/a
D.3.9.2	Current sponsor code	n/a
D.3.9.3	Other descriptive name	n/a
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.9%
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	Sterile saline solution for injection (0.9% sodium chloride) supplied as a 0.5-mL dose.
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Havrix Junior Monodose Vaccine
D.2.1.1.2	Name of the Marketing Authorisation holder	SmithKline Beecham Plc
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/a
D.3.9.1	CAS number	N/a
D.3.9.2	Current sponsor code	N/a
D.3.9.3	Other descriptive name	N/a
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit/ml enzyme-linked immunosorbent assay unit/millitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	720
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 4
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Havrix Monodose Vaccine
D.2.1.1.2	Name of the Marketing Authorisation holder	SmithKline Beecham Plc
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	N/a
D.3.9.1	CAS number	N/a
D.3.9.2	Current sponsor code	N/a
D.3.9.3	Other descriptive name	N/a
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit/ml enzyme-linked immunosorbent assay unit/millitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1440
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

BACTERIAL MENINGITIS.

E.1.1.1

Medical condition in easily understood language

BACTERIAL MENINGITIS.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10004049
E.1.2	Term	Bacterial meningitis
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Primary:
 To assess the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 4 primary MnB test strains, 2 expressing an LP2086 subfamily A protein and 2 expressing an LP2086 subfamily B protein, measured 1 month after the third vaccination with bivalent rLP2086 vaccine.
 To demonstrate that the immune responses induced by 3 lots of bivalent rLP2086 vaccine are equivalent as measured by hSBA performed with 2 primary MnB test strains, 1 expressing an LP2086 subfamily A protein and 1 expressing an LP2086 subfamily B protein, 1 month after the third vaccination with bivalent rLP2086 vaccine.
Primary Safety:
 To evaluate the safety profile of bivalent rLP2086 vaccine compared to a control (HAV/saline), as measured by local reactions, systemic events, AEs, SAEs, newly diagnosed chronic medical conditions, medically attended AEs, and immediate AEs.

E.2.2

Secondary objectives of the trial

 To describe the immune response as measured by hSBA performed with 10 secondary MnB test strains expressing LP2086 subfamily A or B proteins, measured 1 month after the third vaccination with bivalent rLP2086 vaccine.
 To describe the immune response as measured by hSBA performed with 4 primary MnB test strains, 2 expressing a LP2086 subfamily A protein and 2 expressing a LP2086 subfamily B protein, measured 1 month after the second vaccination with bivalent rLP2086 vaccine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator’s study team before subjects are included in the study. Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Evidence of a personally signed and dated informed consent document indicating that the subject (and/or parent/legally authorized representative) has been informed of all pertinent aspects of the study.
2. Parent/legally authorized representative and/or subjects who are willing and able to comply with scheduled visits, laboratory tests, and other study procedures.
3. Male or female subject aged ≥10 and <19 years at the time of enrollment.
4. Available for the entire study period and can be reached by telephone.
5. Healthy subject as determined by medical history, physical examination, and judgment of the investigator.
6. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study (through the follow-up telephone contact at month 12). A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active. Refer to Section Protocol 4.5 for further information.
7. Negative urine pregnancy test for all female subjects.

E.4

Principal exclusion criteria

Subjects presenting with any of the following will not be included in the study:
1. Previous vaccination with any meningococcal serogroup B vaccine.
2. A previous anaphylactic reaction to any vaccine or vaccine-related component.
3. Subjects who have received prior HAV vaccination.
4. Contraindication to vaccination with any HAV vaccine.
5. Subjects who are scheduled to receive 1 or more doses of an HPV vaccine as part of a 3-dose series during the period between Visit 1 and 28 days after the second vaccination.
6. Subjects receiving any allergen immunotherapy with a nonlicensed product or receiving allergen immunotherapy with a licensed product and are not on stable maintenance doses.
7. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.
8. A known or suspected defect of the immune system that would prevent an immune response to the vaccine, such as subjects with congenital or acquired defects in B cell function, those receiving chronic systemic (oral, intravenous, or intramuscular) corticosteroid therapy, or those receiving immunosuppressive therapy. Subjects in the United States with terminal complement deficiency are excluded from participation in this study. Please refer to the SRM for additional details.
9. History of microbiologically proven disease caused by Neisseria meningitidis or Neisseria gonorrhoeae.
10. Significant neurological disorder or history of seizure (excluding simple febrile seizure).
11. Receipt of any blood products, including immunoglobulin within 6 months before the first study vaccination.
12. Current chronic use of systemic antibiotics.
13. Current participation in another investigational study. Participation in purely observational studies is acceptable.
14. Received any investigational vaccines, drugs, or devices within 28 days before administration of the first study vaccination.
15. Any neuroinflammatory or autoimmune condition, including, but not limited to, transverse myelitis, uveitis, optic neuritis, and multiple sclerosis.
16. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
17. Subjects who are investigational site staff members or relatives of those site staff members, or subjects who are Pfizer employees directly involved in the conduct of the trial.
18. Subject is pregnant or breastfeeding.

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoints
Five (5) coprimary endpoints are defined for the primary immunogenicity objective based upon results for group 1 subjects in hSBAs performed with each of the 4 primary test strains: PMB80 (A22), PMB2001 (A56), PMB2948 (B24), PMB2707 (B44).
 One (1) of the 5 coprimary endpoints is the composite endpoint defined as the proportion of subjects achieving an hSBA titer ≥ lower limit of quantitation (LLOQ) for all 4 primary test strains combined, 1 month after the third vaccination with bivalent rLP2086 vaccine.
 Four (4) of the coprimary endpoints are defined as the proportion of subjects achieving at least a 4-fold increase in hSBA titer from baseline to 1 month after the third vaccination with bivalent rLP2086 vaccine for each of the 4 primary test strains.
 For subjects with a baseline hSBA titer below the limit of detection (LOD or an hSBA titer of < 1:4), a 4-fold response is defined as an hSBA titer of ≥1:16 or the LLOQ (whichever titer is higher).
 For subjects with a baseline hSBA titer of ≥ LOD (ie, hSBA titer of ≥1:4) and < lower limit of quantitation (LLOQ), a 4-fold response is defined as an hSBA titer ≥4 times the LLOQ.
 For subjects with a baseline hSBA titer of ≥ LLOQ, a 4-fold response is defined as an hSBA titer of ≥4 times the baseline titer.
 The endpoints for the lot consistency objective are hSBA geometric mean titers (GMTs) for each of the 2 primary test strains PMB80 (A22) and PMB2948 (B24) measured 1 month after the third vaccination with bivalent rLP2086 vaccine in group 1, group 2, and group 3.

Safety Endpoints
 Percentage of subjects reporting local reactions (pain, redness and swelling) and by severity after each vaccination visit.
 Percentage of subjects reporting systemic events (fever, vomiting, diarrhea, headache, fatigue, chills, muscle pain other than muscle pain at any injection site, and joint pain) and by severity after each vaccination visit.
 Percentage of subjects reporting the use of antipyretic medication after each vaccination visit.
 Percentage of subjects with at least 1 SAE during the following time periods:
 30 Days after each vaccination.
 30 Days after any vaccination.
 During the vaccination phase (from the first study vaccination [Visit 1] through 1 month after the last study vaccination [Visit 5]).
 During the follow-up phase (from 1 month after the last study vaccination [Visit 5] through 6 months after the third study vaccination [Visit 6]).
 Throughout the study period (from the first study vaccination [Visit 1] through 6 months after the third study vaccination [Visit 6]).
 Percentage of subjects with at least 1 medically attended AE occurring during the following time periods:
 30 Days after each vaccination.
 30 Days after any vaccination.
 During the vaccination phase (from the first study vaccination [Visit 1] through 1 month after the last study vaccination [Visit 5]).
 During the follow-up phase (from 1 month after the last study vaccination [Visit 5] through 6 months after the third study vaccination [Visit 6]).
 Throughout the study period (from the first study vaccination [Visit 1] through 6 months after the third study vaccination [Visit 6]).
 Percentage of subjects with at least 1 newly-diagnosed chronic medical condition occurring during the following time periods:
 30 Days after each vaccination.
 30 Days after any vaccination.
 During the vaccination phase (from the first study vaccination [Visit 1] through 1 month after the last study vaccination [Visit 5]).
 During the follow-up phase (from 1 month after the last study vaccination [Visit 5] through 6 months after the third study vaccination [Visit 6]).
 Throughout the study period (from the first study vaccination [Visit 1] through 6 months after the third study vaccination [Visit 6]).
 Percentage of subjects who develop at least 1 AE occurring during the following time periods:
 30 Days after each vaccination.
 30 Days after any vaccination.
 During the vaccination phase (from the first study vaccination [Visit 1] through 1 month after the last study vaccination [Visit 5]).
 Percentage of subjects reporting at least 1 immediate AE after each vaccination.
 Subject days missing school or work due to AEs during the vaccination phase (Visit 1 though Visit 5).

E.5.1.1

Timepoint(s) of evaluation of this end point

No interim analysis is planned for this study. Only one final analysis will be performed on the final locked study database and will include all of the immunogenicity and safety analysis results related to the primary and secondary objectives

E.5.2

Secondary end point(s)

The secondary strain immunogenicity objective is based on hSBA results from subjects in group 1 using 10 test strains expressing the following variants: A29, A06, A12, A07, A15, A19, B16, B09, B03, B15. Three (3) subsets of study subjects will be selected for this analysis. Each subset will be used to assess the response to 3 or 4 of the 10 secondary test strains in addition to the 4 primary test strains.
The secondary immunogenicity endpoints for the subsets tested with the secondary hSBA test strains are:
 Proportions of subjects with hSBA titers ≥ LLOQ for each of the test strains at baseline and 1 month after the third vaccination with bivalent rLP2086 vaccine.
 Proportions of subjects with hSBA titers ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the test strains at baseline and 1 month after the third vaccination with bivalent rLP2086 vaccine.
 hSBA geometric mean titers (GMTs) for each of the test strains at baseline and 1 month after the third vaccination with bivalent rLP2086 vaccine.

For group 1 subjects, additional secondary immunogenicity endpoints will include:
 Proportion of subjects with a composite hSBA response, defined as subjects with an hSBA titer of ≥ LLOQ for all 4 primary test strains, at baseline.
 Proportion of subjects achieving a composite hSBA response, defined as subjects achieving an hSBA titer of ≥ LLOQ for all 4 primary test strains, at 1 month after the second vaccination with bivalent rLP2086 vaccine.

For subjects in groups 1, 2, and 3, additional secondary immunogenicity endpoints will include:
 Proportion of subjects achieving at least a 4-fold increase in hSBA titer from baseline to 1 month after the second vaccination with bivalent rLP2086 vaccine for each of the 4 primary test strains (group 1) and from baseline to 1 month after the second and third vaccinations with bivalent rLP2086 vaccine for PMB80 (A22) and PMB2948 (B24) (group 2 and group 3), using the following definition:
 For subjects with a baseline hSBA titer below the limit of detection (LOD or an hSBA titer of <1:4), a 4-fold response is defined as an hSBA titer of ≥1:16 or the LLOQ (whichever titer is higher).
 For subjects with a baseline hSBA titer of ≥ LOD (ie, hSBA titer of ≥1:4) and < lower limit of quantitation (LLOQ), a 4-fold response is defined as an hSBA titer of ≥4 times the LLOQ.
 For subjects with a baseline hSBA titer of ≥ LLOQ, a 4-fold response is defined as an hSBA titer of ≥4 times the baseline titer.
 hSBA geometric mean titers (GMTs) for each of the 4 primary test strains (group 1) and for PMB80 (A22) and PMB2948 (B24) (group 2 and group 3), at baseline and 1 month after the second vaccination with bivalent rLP2086 vaccine.
 Proportions of subjects achieving hSBA titers of ≥LLOQ, ≥1:4, ≥1:8, ≥1:16, ≥1:32, ≥1:64, and ≥1:128 for each of the 4 primary test strains (group 1) and for PMB80 (A22) and PMB2948 (B24) (group 2 and group 3), at baseline, 1 month after the second, and 1 month after the third vaccination with bivalent rLP2086 vaccine.
 Proportion of subjects achieving at least a 3-fold increase in hSBA titer from baseline to 1 month after the third vaccination with bivalent rLP2086 vaccine for each of the 4 primary test strains (group 1) and for PMB80 (A22) and PMB2948 (B24) (group 2 and group 3), using the following definition:
 For subjects with a baseline hSBA titer below the limit of detection (LOD or a hSBA titer of <1:4), a response is defined as an hSBA titer ≥1:16 or the LLOQ (whichever titer is higher).
 For subjects with a baseline hSBA titer of ≥ LOD (ie, hSBA titer of ≥1:4) and < lower limit of quantitation (LLOQ), a 3-fold response is defined as an hSBA titer of ≥3 times LLOQ.
 For subjects with a baseline hSBA titer of ≥ LLOQ, a 3-fold response is defined as an hSBA titer of ≥3 times baseline hSBA titer.
 Proportion of subjects achieving at least a 2-fold increase from baseline to 1 month after the third vaccination with bivalent rLP2086 vaccine for each of the 4 primary test strains (group 1) and for PMB80 (A22) and PMB2948 (B24) (group 2 and group 3), using the following definition:
 For subjects with a baseline hSBA titer below the limit of detection (LOD or an hSBA titer of <1:4), a response is defined as an hSBA titer of ≥1:16 or the LLOQ (whichever titer is higher).
 For subjects with a baseline hSBA titer of ≥ LOD (ie, hSBA titer of ≥1:4) and < lower limit of quantitation (LLOQ), a 2-fold response is defined as an hSBA titer of ≥2 times LLOQ.
 For subjects with a baseline hSBA titer of ≥ LLOQ, a 2-fold response is defined as an hSBA titer of ≥2 times baseline hSBA titer.

E.5.2.1

Timepoint(s) of evaluation of this end point

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

CONSISTENCY, TOLERABILITY & IMMUNOGENICITY

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

Czech Republic

Finland

Germany

Italy

Poland

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

End of Trial in a Member State:
End of Trial in a Member State of the European Union is defined as the time at which it is deemed that sufficient subjects have been recruited and completed the study as stated in the regulatory application (ie, Clinical Trial Application (CTA)) and ethics application in the Member State.

End of Trial in all Participating Countries:
The end of the clinical phase of the study will be the last telephone contact (Visit 6) to the last subject.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

3510

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

3420

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

All male and female subjects must agree to practice a form of effective contraception.

F.4 Planned number of subjects to be included

F.4.1

In the member state

464

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1589

F.4.2.2

In the whole clinical trial

3600

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-04-14

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