Trial Outcomes & Findings for A Study to Assess Immune Response Following Zoster Vaccination to Subjects With Rheumatoid Arthritis Receiving Tofacitinib or Placebo With Background Methotrexate (NCT NCT02147587)
NCT ID: NCT02147587
Last Updated: 2018-04-11
Results Overview
VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA).
COMPLETED
PHASE2
112 participants
Baseline (pre-vaccination; Day -14), Week 4 (6 weeks post-vaccination)
2018-04-11
Participant Flow
The zoster vaccine was administered at least 2 weeks (14 to 21 days) prior to initiation of CP-690,550 (tofacitinib) or placebo in rheumatoid arthritis (RA) participants on background methotrexate therapy.
Participant milestones
| Measure |
Placebo Twice a Day
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
57
|
55
|
|
Overall Study
COMPLETED
|
46
|
50
|
|
Overall Study
NOT COMPLETED
|
11
|
5
|
Reasons for withdrawal
| Measure |
Placebo Twice a Day
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
9
|
4
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
Baseline Characteristics
A Study to Assess Immune Response Following Zoster Vaccination to Subjects With Rheumatoid Arthritis Receiving Tofacitinib or Placebo With Background Methotrexate
Baseline characteristics by cohort
| Measure |
Placebo Twice a Day
n=57 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
Total
n=112 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.0 years
STANDARD_DEVIATION 8.7 • n=5 Participants
|
61.7 years
STANDARD_DEVIATION 6.2 • n=7 Participants
|
61.8 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
38 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
80 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (pre-vaccination; Day -14), Week 4 (6 weeks post-vaccination)Population: The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.
VZV-specific IgG levels as measured by enzyme-linked immunosorbent assay (ELISA).
Outcome measures
| Measure |
Placebo Twice a Day
n=53 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=54 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Fold Change From Baseline in Varicella Zoster Virus (VZV)-Specific Immunoglobulin G (IgG) Levels at Week 4
|
1.736 fold rise
Interval 1.546 to 1.95
|
2.105 fold rise
Interval 1.871 to 2.369
|
SECONDARY outcome
Timeframe: Baseline (pre-vaccination; Day -14), Day 1 (2 weeks post-vaccination), Week 12 (14 weeks post-vaccination)Population: The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.
Outcome measures
| Measure |
Placebo Twice a Day
n=53 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=54 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12
Day 1
|
1.947 fold rise
Interval 1.733 to 2.186
|
2.005 fold rise
Interval 1.782 to 2.256
|
|
Fold Change From Baseline in VZV-Specific IgG Levels at Day 1 and Week 12
Week 12
|
1.496 fold rise
Interval 1.323 to 1.691
|
1.636 fold rise
Interval 1.448 to 1.847
|
SECONDARY outcome
Timeframe: Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)Population: The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.
The absolute geometric mean titer (GMT) of VZV-specific IgG levels was calculated from logarithmically transformed assay values.
Outcome measures
| Measure |
Placebo Twice a Day
n=53 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=54 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12
Day 1
|
361.603 [gp]ELISA units/mL
Interval 300.012 to 435.838
|
384.219 [gp]ELISA units/mL
Interval 317.477 to 464.993
|
|
Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12
Week 4
|
322.486 [gp]ELISA units/mL
Interval 267.557 to 388.69
|
403.422 [gp]ELISA units/mL
Interval 333.343 to 488.232
|
|
Absolute Values in VZV-Specific IgG Levels at Day 1, Week 4 and Week 12
Week 12
|
278.599 [gp]ELISA units/mL
Interval 229.984 to 337.489
|
312.328 [gp]ELISA units/mL
Interval 257.319 to 379.096
|
SECONDARY outcome
Timeframe: Day 1 (2 weeks post-vaccination), Week 4 (6 weeks post-vaccination), Week 12 (14 weeks post-vaccination)Population: The evaluable immunogenicity analysis population included randomized participants who had at least 1 dose of study drug (tofacitinib or placebo) and who complied closely with protocol eligibility criteria, visit windows for study procedures, had valid assay results at the primary visits and no major protocol deviations.
VZV-specific IgG levels as measured by ELISA. A ratio greater than or equal to (\>=)1.5 was defined as a responder.
Outcome measures
| Measure |
Placebo Twice a Day
n=53 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=54 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12
Week 4
|
43.40 percentage of participants
Interval 34.06 to 53.13
|
57.41 percentage of participants
Interval 47.77 to 66.61
|
|
Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12
Day 1
|
47.17 percentage of participants
Interval 37.66 to 56.85
|
55.56 percentage of participants
Interval 45.93 to 64.86
|
|
Percentage of Participants With >=1.5 Fold Change in VZV-Specific IgG Levels Day 1, Week 4 and Week 12
Week 12
|
43.18 percentage of participants
Interval 32.9 to 53.96
|
45.83 percentage of participants
Interval 35.87 to 56.07
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to Week 16Population: The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).
An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 16 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-SAEs.
Outcome measures
| Measure |
Placebo Twice a Day
n=57 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
AEs
|
21 participants
|
16 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
SAEs
|
0 participants
|
3 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to Week 16Population: The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).
Zoster vaccine-related AEs included General Disorders and Administration Site Conditions (injection site erythema, pain, pruritis, rash, swelling; vaccination site erythema, pruritus, rash), Infections and Infestations (disseminated herpes zoster), and Musculoskeletal and Connective Tissue Disorders (myalgia). All zoster vaccine-related AEs were mild, except for the herpes zoster AE classified under Infections and Infestations, which was moderate in severity.
Outcome measures
| Measure |
Placebo Twice a Day
n=57 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Number of Participants With Zoster Vaccine-Related AEs by System Organ Class
General and Administration Site Conditions
|
2 participants
|
4 participants
|
|
Number of Participants With Zoster Vaccine-Related AEs by System Organ Class
Infections and Infestations
|
0 participants
|
1 participants
|
|
Number of Participants With Zoster Vaccine-Related AEs by System Organ Class
Musculoskeletal and Connective Tissue Disorders
|
0 participants
|
1 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to Week 16Population: The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).
Clinical herpes is manifested as mild, moderate, or severe disseminated herpes zoster.
Outcome measures
| Measure |
Placebo Twice a Day
n=57 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Number of Participants With Clinical Herpes Zoster Events by Severity
Mild Herpes Zoster
|
0 participants
|
0 participants
|
|
Number of Participants With Clinical Herpes Zoster Events by Severity
Moderate Herpes Zoster
|
0 participants
|
1 participants
|
|
Number of Participants With Clinical Herpes Zoster Events by Severity
Severe Herpes Zoster
|
0 participants
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline up to Week 16Population: The safety analysis population included randomized participants who received at least 1 dose of the study drug (tofacitinib or placebo).
Participants with the following abnormalities were discontinued from the study: 2 sequential absolute neutrophil counts (ANC) \<1000/mm\^3; 2 sequential hemoglobin values \<8.0 g/dL or decreases of \>30% from baseline value; 2 sequential absolute lymphocyte count \<500/mm\^3; 2 sequential platelet counts \<75,000/mm\^3; 2 sequential alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevations \>=3 times the upper limit of normal (X ULN) with a total bilirubin value \>=2X ULN, elevated international normalized ratio (INR), or accompanied by signs/symptoms consistent with hepatic injury; 2 sequential ALT or AST elevations \>=5X ULN regardless of total bilirubin or accompanying symptoms; confirmed increases in serum creatinine (SCr) \>50% over the average of screening and baseline values; a confirmed positive urine pregnancy test or refusal to use appropriate contraception in a woman of childbearing potential.
Outcome measures
| Measure |
Placebo Twice a Day
n=57 Participants
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 Participants
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Number of Participants With Clinically Significant Abnormal Laboratory Parameters
|
1 participants
|
0 participants
|
Adverse Events
Placebo Twice a Day
Tofacitinib 5 mg Twice a Day
Serious adverse events
| Measure |
Placebo Twice a Day
n=57 participants at risk
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 participants at risk
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Hepatobiliary disorders
Bile duct stone
|
0.00%
0/57 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
1.8%
1/55 • Number of events 1 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/57 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
1.8%
1/55 • Number of events 1 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
|
Infections and infestations
Bronchitis
|
0.00%
0/57 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
1.8%
1/55 • Number of events 1 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
|
Infections and infestations
Herpes zoster disseminated
|
0.00%
0/57 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
1.8%
1/55 • Number of events 1 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
Other adverse events
| Measure |
Placebo Twice a Day
n=57 participants at risk
Following administration of zoster vaccine, participants with Rheumatoid Arthritis (RA) on background methotrexate received placebo matched tofacitinib tablets twice a day orally for up to 12 weeks.
|
Tofacitinib 5 mg Twice a Day
n=55 participants at risk
Following administration of zoster vaccine to RA participants receiving background methotrexate, participants received tofacitinib 5 mg twice a day orally for up to 12 weeks.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/57 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
5.5%
3/55 • Number of events 3 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
15.8%
9/57 • Number of events 9 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
5.5%
3/55 • Number of events 3 • Baseline up to Week 16
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER