Clinical Trials Register

Summary
EudraCT Number:	2013-002145-11
Sponsor's Protocol Code Number:	B1971015(6108A1-2005)
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2013-05-23
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2013-002145-11

A.3

Full title of the trial

A Phase 2, Randomized, Active-controlled, observer-blindED Trial, to Assess the Safety, Tolerability, and Immunogenicity of MCV4, TDAP Vaccine and bivalent RLP2086 Vaccine When Administered Concomitantly in Healthy Subjects Aged ≥10 to <13 Years

A.3.1

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

A clinical study evaluating the safety, tolerability, and immune response to MCV4 and TDAP vaccine given together with Bivalent RLP2086 vaccine in healthy subjects ≥ 10 to < 13 years of age.

A.4.1

Sponsor's protocol code number

B1971015(6108A1-2005)

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/013/2013

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Pfizer Inc
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
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 Center
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	NY10017
B.5.3.4	Country	United States
B.5.4	Telephone number	0018007181021
B.5.5	Fax number	0013037391119
B.5.6	E-mail	ClinicalTrials.govCallCenter@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	Neisseria meningitidis Serogroup B Bivalent Recombinant Lipoprotein
D.3.2	Product code	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.3.11 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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Suspension for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MnB) in adolescents and young adults, aged 10 through 25 years.

E.1.1.1

Medical condition in easily understood language

Prevent invasive disease caused by Neisseria meningitidis serogroup B

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
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

demonstrate immune response(based on geometric mean titer GMT)induced by MCV4 and Tdap vaccines given with bivalent rLP2086 vaccine(Group1)is noninferior to immune response induced by MCV4 and Tdap vaccines alone(Group2)when measured 1month after first vaccination(Visit2)in both groups. Immune response to all components of MCV4 and Tdap vaccines will be assessed.
demonstrate immune response (based on GMT)induced by bivalent rLP2086 vaccine,as measured by serum bactericidal assay using human complement(hSBA)performed with 2MnB strains, 1expressing LP2086 subfamily A and 1expressing LP2086 subfamily B proteins,given with MCV4 and Tdap vaccines(Group1)is noninferior to the immune response induced by bivalent rLP2086 vaccine alone(Group3),when measured 1month after the third vaccination(Visit6)with bivalent rLP2086 vaccine in both groups
evaluate safety profile of bivalent rLP2086 vaccine as measured by proportion of subjects reporting local reactions,systemic events,adverse events

E.2.2

Secondary objectives of the trial

To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 2 MnB strains, one expressing LP2086 subfamily A and one expressing LP2086 subfamily B proteins, measured 1 month after the third vaccination (Visit 6) with bivalent rLP2086 vaccine (Group 3).

To describe the immune response as measured by serum bactericidal assay using human complement (hSBA) performed with 2 MnB strains, one expressing LP2086 subfamily A and one expressing LP2086 subfamily B proteins, measured 1 month after the second vaccination (Visit 4) with bivalent rLP2086 vaccine (Group 3)

To describe the seroresponses to antigens contained in MCV4 and Tdap (Groups 1 and 2) when measured 1 month after vaccination with MCV4 and Tdap (Visit 2)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Evidence of a personally signed and dated informed consent document (ICD) indicating that the subject (and a legally authorized representative) has been informed of all pertinent aspects of the study.
2. Parent /legally authorized representative and 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 <13 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. Has received full series (5-dose series is preferred, 4-dose catch up series is allowed) of diphtheria, tetanus and pertussis (whole cell or acellular) vaccines per country specific recommendations applicable at the time of receipt.
7. Male and female subjects of childbearing potential must agree to use a highly effective method of contraception throughout the study (through the follow-up phone 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 4.5 for further information.
8. Negative urine pregnancy test for all female subjects.

E.4

Principal exclusion criteria

1. Previous vaccination with any meningococcal serogroup B vaccine.
2. Vaccination with any diphtheria, tetanus or pertussis vaccine within 5 years of the first study vaccination.
3. Previous vaccination with any MCV4 vaccine.
4. A previous anaphylactic reaction to any vaccine or vaccine-related component.
5. Contraindication to vaccination with MCV4 and/or Tdap vaccine.
6. Subjects receiving any allergen immunotherapy with a non-licensed 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 with terminal complement deficiency may not be included.
9. History of culture-proven disease caused by Neisseria meningitidis or Neisseria gonorrhoea.
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. Participation in other studies during study participation. Participation in purely observational studies is acceptable.
14. Received any investigational drugs, vaccines 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 who are Pfizer employees directly involved in the conduct of the trial or relatives of those Pfizer employees.
18. Subject is pregnant or breastfeeding.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoints for the co-primary objectives are:
The primary endpoints for the first co-primary objective are the geometric mean titers (GMTs) or geometric mean concentrations (GMCs) for each of the antibodies reactive with each of the 10 antigenic components in the marketed vaccines at visit 2, among subjects in Groups 1 and 2
The primary endpoints for the second co-primary objective are the hSBA GMTs for each of the 2 primary strains (PMB80 [A22] and PMB2948 [B24]) at visit 6, among subjects in Groups 1 and 3.

Primary Endpoints : GMs
Marketed Vaccine Components
Meningococcal serogroup A : GMT
Meningococcal serogroup C : GMT
Meningococcal serogroup Y : GMT
Meningococcal serogroup W-135 : GMT
Diphtheria : GMC
Tetanus : GMC
Pertussis toxoid (PT) : GMC
Pertussis filamentous hemagglutinin (FHA) : GMC
Pertussis pertactin (PRN) : GMC
Pertussis fimbriae types 2 and 3 (FIM) : GMC
rLP2086 Vaccine Strains
PMB80 (A22) : GMT
PMB2948 (B24) : GMT

All of the safety endpoints will be applied to each group.
• Proportion of subjects reporting local reactions (pain, redness and swelling) and by severity after each vaccination visit.
• Proportion 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.
• Proportion of subjects reporting the use of antipyretic medication after each vaccination visit.
• Proportion of subjects who develop at least one adverse event 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 6)]
• Proportion of subjects with at least one 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 6)]
• During the follow-up phase [from 1 month after the last study vaccination (Visit 6) through 6 months after the third study vaccination (Visit 7)]
• Throughout the study period [from the first study vaccination (Visit 1) through 6 months after the third study vaccination (Visit 7)].
• Proportion of subjects reporting at least one immediate adverse event after each vaccination.
• Proportion of subjects reporting at least one newly diagnosed major illness, during the follow-up phase [from 1 month after the last study vaccination (Visit 6) through 6 months after the third study vaccination (Visit 7)].

E.5.1.1

Timepoint(s) of evaluation of this end point

• One month post vaccination 1 and last vaccination for first and secondary co-primary immunogenicity endpoint

Safety Endpoints
Local Reactions, Systemic Events, Antipyretic Use
• 7days after each vaccination

AE’s
• 30 days after each/any vaccination
• During vaccination [from first through 1 month after last study vaccination ]
SAE’s
• 30 days after each/any vaccination
• During vaccination [from first through 1 month after last study vaccination ]
• During the follow-up [from 1 month after last through 6 months after third study vaccination ]
• Throughout study [from first through 6 months after third study vaccination
Immediate AE’s
• 30min after each vaccination
Newly Diagnosed Major Illness
• 1 month after last through 6 months after third study vaccination

E.5.2

Secondary end point(s)

• The seroresponse rate at visit 2 for each of the 10 marketed vaccine antigens in Group 1 and Group 2.
• For Tdap vaccine, the booster response is used, which is defined as at least 4-fold rise in antibody concentration if the pre-vaccination concentration is ≤ cutoff value and at least 2-fold rise in antibody concentration if the pre-vaccination concentration is > cutoff value. The cutoff values are described as below:

Table 1. Cutoff for Booster Response

Antigens : Cutoff
Tdap
Diphtheria : 0.1 IU/mL
Tetanus : 0.1 IU/mL
Pertussis toxoid (PT) : 0.9 EU/mL
Pertussis filamentous hemagglutinin (FHA) : 2.9 EU/mL
Pertussis pertactin (PRN) : 3.0 EU/mL
Pertussis fimbriae types 2 and 3 (FIM) : 10.6 EU/mL

• For MCV4, the seroconversion rate is used, which is defined as ≥4-fold rise on serum bactericidal assay using rabbit complement (rSBA) titers
• Proportion of subjects (Groups 1 and 2) who achieve an antibody level ≥1.0 IU/mL to tetanus and proportion of subjects (Groups 1 and 2) who achieve an antibody level ≥1.0 IU/mL to diphtheria toxoid
• hSBA titers as measured by GMTs for each of the 2 primary MnB test strains (PMB80 [A22] and PMB2948 [B24]) at each applicable blood sampling time point
• Proportion of subjects with hSBA titers ≥LLOQ, ≥1:4, ≥1:8, ≥1:16 , ≥1:32, ≥1:64, ≥1:128 at each blood draw visit, for each of the 2 primary strains (PMB80 [A22] and PMB2948 [B24])

E.5.2.1

Timepoint(s) of evaluation of this end point

• One month after vaccination 1.
• One month after vaccination 1.
• One month after vaccination 1.
• One month after first, second, and third vaccination.
• One month after first, second, and third vaccination

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

observer blinded

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

saline, MCV4 and Tdap

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

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

The end of the clinical phase of the study will be the telephone contact to the last subject. At this time, sites will be closed out, the institutional review board/independent ethics committee (IRB/IEC) will be informed, and no further Council for International Organizations of Medical Sciences (CIOMS) reports will be sent. For other purposes, the end of the study will be last serology sample assayed.

E.8.9 Initial estimate of the duration of the trial

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:

2625

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:

1750

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

875

F.1.2

Adults (18-64 years)

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

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

2625

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

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	United States

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