Tick-Borne Encephalitis (TBE) Seropersistence After First Booster and Response to a Second Booster in Children, Adolescents and Young Adults (Follow-Up to Study 700401)

• ClinicalTrials.gov Identifier: NCT00894686
• Recruitment Status: Completed
• First Posted: May 7, 2009
• Results First Posted: December 17, 2018
• Last Update Posted: December 17, 2018
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

The main purpose of this study is to assess the seropersistence of TBE virus antibodies in children, adolescents and young adults who received the first booster vaccination with either FSME-IMMUN 0.25 mL Junior or FSME-IMMUN 0.5 mL in precursor Study 700401.

Condition or disease	Intervention/treatment	Phase
Encephalitis, Tick-Borne	Biological: FSME-IMMUN 0.25 mL Junior (1.2 µg TBE antigen/0.25 mL) or FSME-IMMUN 0.5 mL (2.4µg TBE antigen/0.5 mL)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 179 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Open-label Phase Iv Study To Investigate The Seropersistence Of Tick-borne Encephalitis (Tbe) Virus Antibodies After The First Booster And The Response To A Second Booster Vaccination With Fsme-immun In Children, Adolescents And Young Adults (Follow-up To Study 700401)
• Actual Study Start Date: April 26, 2009
• Actual Primary Completion Date: May 10, 2017
• Actual Study Completion Date: May 10, 2017

Arms and Interventions

Arm

Intervention/treatment

Experimental: All subjects; Assessment of seropersistence of TBE antibodies at yearly intervals from approximately 3 years (38 months) to 10 years (118 months) after the first booster vaccination (in Study 700401), as well as antibody response to a second booster vaccination with either FSME-IMMUN 0.25 mL Junior or FSME-IMMUN 0.5 mL, depending on the subject´s age. Timing of the second booster vaccination will depend on the level of serum TBE antibodies detected at the defined assessment time points. Subjects who are not protected against TBE for an entire further season (NT titer <= 20 and/or ELISA value <=126 VIE U/mL) will be invited to receive the second booster vaccination at either the 40, 48, 60, 72, 84, 96, 108, or 120-month time point.

Biological: FSME-IMMUN 0.25 mL Junior (1.2 µg TBE antigen/0.25 mL) or FSME-IMMUN 0.5 mL (2.4µg TBE antigen/0.5 mL); Dosage form: solution/suspension; injectable. Dosage frequency: once. Mode of administration: intramuscular.

Outcome Measures

Primary Outcome Measures :

1. Seropositivity Rate Measured by Neutralization Test (NT) at 21-35 Days After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 21-35 days after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level greater than equal to (>=) 10 at 21-35 days after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent confidence interval (CI) was based upon the observed percentage of participants.
2. Seropositivity Rate Measured by Neutralization Test (NT) at 38 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 38 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 38 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent confidence interval (CI) was based upon the observed percentage of participants.
3. Seropositivity Rate Measured by Neutralization Test (NT) at 46 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 46 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 46 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
4. Seropositivity Rate Measured by Neutralization Test (NT) at 58 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 58 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 58 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
5. Seropositivity Rate Measured by Neutralization Test (NT) at 70 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 70 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 70 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
6. Seropositivity Rate Measured by Neutralization Test (NT) at 82 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 82 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 82 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
7. Seropositivity Rate Measured by Neutralization Test (NT) at 94 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 94 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 94 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
8. Seropositivity Rate Measured by Neutralization Test (NT) at 106 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 106 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 106 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
9. Seropositivity Rate Measured by Neutralization Test (NT) at 118 Months After the First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 118 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with NT level >=10 at 118 months after the first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
10. Seropositivity Rate Measured by Neutralization Test (NT) at 21-35 Days After the Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 [ Time Frame: 21-35 days after second TBE booster vaccination ]
    Seropositivity rate was reported as percentage of participants with NT level >=10 at 21-35 days after the second TBE booster vaccination. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.

Secondary Outcome Measures :

1. Seropositivity Rate Measured by Enzyme-Linked Immunosorbent Assay (ELISA) at Each Available Time Point After First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 21-35 days and 38, 46, 58, 70, 82, 94, 106, 118 months after first TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with ELISA level greater than (>) 126 vienna units per milliliter (VIE U/mL) at each blood sampling time point after first TBE booster vaccination in Study 700401. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
2. Seropositivity Rate Measured by Enzyme-Linked Immunosorbent Assay (ELISA) at 21-35 Days After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 [ Time Frame: 21-35 days after second TBE booster vaccination ]
   Seropositivity rate was reported as percentage of participants with ELISA level >126 VIE U/mL at 21-35 days after second TBE booster vaccination. Exact 2-sided 95 percent CI was based upon the observed percentage of participants.
3. Geometric Mean Concentration Measured by Enzyme-linked Immunosorbent Assay (ELISA) at Each Available Time-Point After First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 21-35 days and 38, 46, 58, 70, 82, 94, 106, 118 months after first TBE booster vaccination ]
   Antibody against TBE booster vaccination was measured as geometric mean concentration (GMC) by ELISA level at different time points after first booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the concentrations.
4. Geometric Mean Concentration Measured by Enzyme-linked Immunosorbent Assay (ELISA) at 21-35 Days After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 [ Time Frame: 21-35 days after second TBE booster vaccination ]
   Antibody against TBE booster vaccination was measured as GMC by ELISA level after the second booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the concentrations.
5. Geometric Mean Titer Measured by Neutralization Test (NT) Each Available Time-Point Blood Draw After First Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700401 [ Time Frame: 21-35 days and 38, 46, 58, 70, 82, 94, 106, 118 months after first TBE booster vaccination ]
   Antibody against TBE booster vaccination was measured as geometric mean titer (GMT) by NT level at different time points after first booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers.
6. Geometric Mean Titer Measured by Neutralization Test (NT) After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 [ Time Frame: 21-35 days after second TBE booster vaccination ]
   Antibody against TBE booster vaccination was measured as GMT by NT level after second booster vaccination. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers.
7. Geometric Mean Fold Rise (GMFR) in Antibody Concentrations After Second Tick-borne Encephalitis (TBE) Booster Vaccination as Compared to Before the Booster Vaccination as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) [ Time Frame: Before second booster vaccination (pre-vaccination), 21-35 days after second booster vaccination ]
   GMFR in antibody concentration from pre-booster (before second booster vaccination) to post-booster (21-35 days after TBE vaccination) was measured by ELISA. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers, concentrations or the fold rises.
8. Geometric Mean Fold Rise (GMFR) in Antibody Titer After Second Tick-borne Encephalitis (TBE) Booster Vaccination as Compared to Before the Booster Vaccination as Measured by Neutralization Test (NT) [ Time Frame: Before second booster vaccination (pre-vaccination), 21-35 days after second booster vaccination ]
   GMFR in antibody titers from pre-booster (before second booster vaccination) to post-booster (21-35 days after TBE vaccination) was measured by ELISA. CIs were computed by back transforming the CIs based on the Student t distribution for the mean logarithm of the titers, concentrations or the fold rises.
9. Number of Participants With Injection Site Reactions and Systemic Reactions After Second Tick-borne Encephalitis (TBE) Booster Vaccination in Study 700802 [ Time Frame: From second booster vaccination up to 21-35 days after the vaccination ]
   Injection site reactions included swelling, induration, redness, injection site pain, tenderness, ecchymosis and hematoma. Systemic reaction included headache, nausea, vomiting, muscle pain, joint pain, swelling of the lymph nodes, malaise and fatigue. Participants with any injection site reaction and systemic reaction after second TBE booster vaccination in Study 700802 were reported in this outcome measure.

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

Subjects who participated in precursor Study 700401 and meet ALL of the following criteria are eligible for participation in this study:

• Subject / parent(s) / legal guardian(s) provide(s) written informed consent (according to national law);
• Subject provides written assent to the study according to age and capacity of understanding;
• Subject received the first booster vaccination with either FSME-IMMUN 0.25 ml Junior or FSME-IMMUN 0.5 ml during the course of precursor Study 700401;
• Blood was drawn after the first booster vaccination in precursor Study 700401;
• Subject / parent(s) / legal guardian(s) understand(s) the nature of the study and is / are willing to comply with the requirements of the protocol (e.g. return for follow-up visits, completion of the Subject Diary).

Exclusion Criteria:

Subjects who participated in precursor Study 700401 and meet ANY of the following criteria are not eligible for participation in this study:

• Subject received any TBE vaccination since his / her first booster vaccination in precursor Study 700401;
• Subject has a history of infection with or vaccination against other flaviviruses (e.g. Dengue fever, yellow fever, Japanese B encephalitis) since his / her first booster vaccination in precursor Study 700401;
• Subject is known to be HIV positive since his / her first booster vaccination in precursor Study 700401 (a special HIV test is not required for the purpose of the study);
• Subject received a blood product or immunoglobulins within 90 days before any blood draw or in the period between the blood draw and the booster vaccination (as applicable);
• Subject has a known or suspected problem with drug or alcohol abuse (> 4 liters of wine/week or equivalent level of other alcoholic beverages);
• Subject / parent(s) / legal guardian(s) is / are in a dependent relationship with the study investigator or with a study team member. Dependent relationship includes close relatives (i.e., children or grandchildren, partner / spouse, siblings) as well as employees of the investigator or the site conducting the study.

Contacts and Locations

Locations

Austria

Grieskirchnerstr.17

Oberösterreich, Austria

Untergraben 2

Oberösterreich, Austria

Germany

Dr. Ulrich Behre

Baden-Württemberg, Germany

Poland

Niepubliczny Zakład Opieki Zdrowotnej Ośrodek Zdrowia w Lipsku

Zamosc, Poland

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer
• Study Director: Eva-Maria Pöllabauer, MD; Baxter Healthcare Corporation

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] June 25, 2015

Statistical Analysis Plan  [PDF] April 25, 2017

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Poellabauer E, Angermayr R, Behre U, Zhang P, Harper L, Schmitt HJ, Erber W. Seropersistence and booster response following vaccination with FSME-IMMUN in children, adolescents, and young adults. Vaccine. 2019 May 27;37(24):3241-3250. doi: 10.1016/j.vaccine.2019.03.032. Epub 2019 Mar 27.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00894686
• Other Study ID Numbers: 700802; B9371021 ( Other Identifier: Alias Study Number ); 2009-009324-36 ( EudraCT Number )
• First Posted: May 7, 2009
• Results First Posted: December 17, 2018
• Last Update Posted: December 17, 2018
• Last Verified: May 2018

Additional relevant MeSH terms:

Encephalitis, Tick-Borne; Encephalitis; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Tick-Borne Diseases; Virus Diseases; RNA Virus Infections; Flavivirus Infections; Flaviviridae Infections