Vaccination Response in Tecfidera-Treated Versus Interfer... | NCT02097849

NCT02097849

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Non-Pegylated IFN Treated Plus Vaccinations	Active Comparator	Participants on a stable approved dose of a non pegylated IFN for ≥3 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL	Biological: tetanus diphtheria toxoids vaccine Biological: 23-valent pneumococcal polysaccharide vaccine Biological: meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent) Drug: non-pegylated interferon
Tecfidera Treated Plus Vaccinations	Experimental	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥6 months will receive 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL PPSV23 0.5 mL MCV4 0.5 mL	Drug: dimethyl fumarate Biological: tetanus diphtheria toxoids vaccine Biological: 23-valent pneumococcal polysaccharide vaccine Biological: meningococcal polysaccharide diphtheria conjugate vaccine (quadrivalent)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
dimethyl fumarate	Drug	Throughout the study participants will remain on their existing, stable dosing regimen of Tecfidera.	Tecfidera Treated Plus Vaccinations

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Tetanus Responders (≥ 2-Fold Rise) at Day 28 Compared to Prevaccination Level	Percentage of participants with a ≥ 2-fold rise in anti-tetanus serum immunoglobulin G (IgG) levels (responders) from prevaccination to 4 weeks after Td vaccination.	Up to Week 4 (Day 28) postvaccination

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level	Percentage of participants with a ≥ 4-fold rise in anti-tetanus serum IgG levels (responders) from prevaccination to 4 weeks after Td vaccination.	Up to Week 4 (Day 28) postvaccination
Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Medical Director	Biogen	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Research Site		Gilbert	Arizona	85234	United States
Research Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
29159204	Derived	von Hehn C, Howard J, Liu S, Meka V, Pultz J, Mehta D, Prada C, Ray S, Edwards MR, Sheikh SI. Immune response to vaccines is maintained in patients treated with dimethyl fumarate. Neurol Neuroimmunol Neuroinflamm. 2017 Nov 15;5(1):e409. doi: 10.1212/NXI.0000000000000409. eCollection 2018 Jan.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
FG001	Tecfidera Treated Plus Vaccinations

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

DMF
BG00012
Tecfidera

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
BG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	OG00073(54 to 87) OG00168(51 to 82)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Clopper-Pearson Exact		0.692		Difference in proportion	-0.04			2-Sided	95	-0.27	0.19					Superiority or Other

Secondary

Percentage of Tetanus Responders (≥ 4-Fold Rise) at Day 28 Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-tetanus serum IgG levels (responders) from prevaccination to 4 weeks after Td vaccination.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Percentage of Pneumococcal Serotype 3 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Percentage of Pneumococcal Serotype 3 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 3 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Percentage of Pneumococcal Serotype 8 (≥ 2-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Percentage of Pneumococcal Serotype 8 (≥ 4-Fold Rise) Responders Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-pneumococcal serum IgG levels against serotype 8 from prevaccination to 4 weeks (28 days) after PPSV23 vaccination.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Percentage of Meningococcal Serogroup C Responders (≥ 2-Fold Rise) Compared to Prevaccination Level

Percentage of participants with a ≥ 2-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination.

One participant in the IFN group did not have an assessment.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants

Secondary

Percentage of Meningococcal Serogroup C Responders (≥ 4-Fold Rise) Compared to Prevaccination Level

Percentage of participants with a ≥ 4-fold rise in anti-meningococcal serum IgG levels against serotype C from prevaccination to 4 weeks after MCV4 vaccination.

One participant in the IFN group did not have an assessment.

Posted

Number

95% Confidence Interval

percentage of participants

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants

Secondary

Ratio of Serum Tetanus Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after Td vaccination.

Posted

Median

Inter-Quartile Range

ratio

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Ratio of Serum Pneumococcal Antibodies (Serotype 3) Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.

Posted

Median

Inter-Quartile Range

ratio

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Ratio of Serum Pneumococcal Antibodies (Serotype 8) Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after PPSV23 vaccination.

Posted

Median

Inter-Quartile Range

ratio

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Ratio of Serum Meningococcal Antibodies (Serogroup C) Level at Day 28 to Prevaccination

Median serum titer ratios from prevaccination to 4 weeks after MCV4 vaccination.

One participant in the IFN group did not have an assessment.

Posted

Median

Inter-Quartile Range

ratio

Up to Week 4 (Day 28) postvaccination

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Number of Participants Experiencing Vaccination-Emergent Adverse Events (AEs) and Serious AEs

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the participant or required intervention to prevent one of the other outcomes listed in the definition above.

Participants who received at least one vaccination.

Posted

Number

participants

Day 1 to Week 4

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Secondary

Number of Participants With Shifts From Baseline in Hematology

Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high.

n=participants whose baseline value was not low (or high) and who had at least one postbaseline value.

Posted

Number

participants

Screening to Week 4

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Shifts From Baseline in Blood Chemistry

Shift to low includes normal to low, high to low, and unknown to low. Shift to high includes normal to high, low to high, and unknown to high.

n=participants whose baseline value was not low (or high) and who had at least one postbaseline value.

Posted

Number

participants

Screening to Week 4

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Units	Counts
Participants	OG000

Secondary

Number of Participants With Abnormalities in Vital Signs

Temperature increase: > 38 celcius (C) or ≥ 1 C increase from baseline. Pulse increase: > 120 beats per minute (bpm) or > 20 bpm increase from baseline. Pulse decrease: < 50 bpm or > 20 bpm decrease from baseline. Systolic blood pressure (SBP) increase: > 180 millimeters of mercury (mmHg) or > 40 mmHg from baseline. SBP decrease: < 90 mmHg or > 30 mmHg decrease from baseline. Diastolic blood pressure (DBP) increase: > 105 mmHg or > 30 mmHg increase from baseline. DBP decrease: < 50 mmHg or > 20 mmHg decrease from baseline.

Participants who had a baseline assessment and at least one postbaseline assessment.

Posted

Number

participants

Screening to Week 4

ID	Title	Description
OG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.
OG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Non-Pegylated IFN Treated Plus Vaccinations	Participants on a stable approved dose of a non pegylated IFN for ≥ 3 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.			0	33	14	33
EG001	Tecfidera Treated Plus Vaccinations	Participants on a stable approved dose of Tecfidera (240 mg BID) for ≥ 6 months received 3 vaccinations on Day 1 intramuscularly in the specified order: Td 0.5 mL; PPSV23 0.5 mL; MCV4 0.5 mL.			0	38	11	38

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site erythema	General disorders	MedDRA 19.0	Systematic Assessment	EG0004 affected33 at risk EG0015 affected38 at risk
Injection site pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0007 affected33 at risk EG0018 affected38 at risk
Injection site swelling	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected33 at risk EG0013 affected38 at risk
Injection site warmth	General disorders	MedDRA 19.0	Systematic Assessment	EG0000 affected33 at risk EG0012 affected38 at risk
Pain	General disorders	MedDRA 19.0	Systematic Assessment	EG0003 affected33 at risk EG0011 affected38 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected33 at risk EG0012 affected38 at risk
Urinary tract infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0002 affected33 at risk EG0010 affected38 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected33 at risk EG0010 affected38 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected33 at risk EG0010 affected38 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected33 at risk EG0011 affected38 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 19.0	Systematic Assessment	EG0002 affected33 at risk EG0010 affected38 at risk

ID	Term
D000069462	Dimethyl Fumarate
D022422	Diphtheria-Tetanus Vaccine
C414006	23-valent pneumococcal capsular polysaccharide vaccine
D022401	Meningococcal Vaccines

Ancestor Terms

ID	Term
D005650	Fumarates
D003998	Dicarboxylic Acids
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D009930	Organic Chemicals
D001428	Bacterial Vaccines
D014612	Vaccines
D001688	Biological Products
D045424	Complex Mixtures
D004168	Diphtheria Toxoid
D014121	Toxoids
D013745	Tetanus Toxoid
D017778	Vaccines, Combined

Units	Counts
Participants	OG00033 OG00138