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Long-Term Effectiveness And Safety Of CP-690,550 For The Treatment Of Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT00413699
Recruitment Status : Completed
First Posted : December 20, 2006
Results First Posted : March 27, 2018
Last Update Posted : July 10, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

The purpose of this study is to determine the long-term effectiveness and safety of CP-690,550 for the treatment of rheumatoid arthritis. Subjects are eligible for this study only after participating in another "qualifying" study of CP-690,550

A sub-study will be conducted within the A3921024 study, this study will evaluate the immune response to pneumococcal and influenza vaccines in patients receiving CP-690,550


Condition or disease Intervention/treatment Phase
Arthritis, Rheumatoid Drug: CP-690,550 Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4553 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Long-term, Open-label Follow-up Study Of Tofacitinib (Cp-690,550) For Treatment Of Rheumatoid Arthritis
Actual Study Start Date : February 5, 2007
Actual Primary Completion Date : November 30, 2016
Actual Study Completion Date : October 26, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Open-Label Active Treatment Enrolled from Phase 2
Patients enrolling from Phase 2 studies
Drug: CP-690,550
5 mg PO BID open label; may increase to 10 mg PO BID to provide greater control of RA if no related AEs are present. May be off study drug temporarily for up to 28 days for mild to moderate AEs.

Experimental: Open-Label Active Treatment Enrolled from Phase 3
Patients enrolling from Phase 3 studies
Drug: CP-690,550
10 mg PO BID open label; may decrease to 5 mg PO BID for mild to moderate AEs. May be off study drug temporarily for up to 28 days for mild to moderate AEs.




Primary Outcome Measures :
  1. Primary Endpoints Were Standard Laboratory Safety Data (Chemistry, Hematology, Etc.) and Adverse Event (AE) Reports [ Time Frame: Includes laboratory test abnormality data for all visits and adverse event data up to 999 days after last dose of study drug ]

    Treatment-emergent non serious AEs by System Organ Class (SOC) (all causalities) and Laboratory Test Abnormalities (without regard to baseline) The stated number of participants analyzed was the total number of participants in each group (AEs). The actual number of participants analyzed for each laboratory parameter varied, and is provided for each.

    Abs=absolute; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ESR=erythrocyte sedimentation rate; GGT=gamma glutamyl transferase; hgb=hemoglobin; HDL=high density lipids; LDL=low density lipids; LLN=lower limit of normal; qual=qualitative; Tot=total; ULN=upper limit of normal; WBC=white blood cell


  2. The Long-term Safety and Tolerability of CP-690,550 5 Milligrams (mg) Twice Daily (BID) and 10 mg BID for the Treatment of Rheumatoid Arthritis [ Time Frame: Includes AEs for every visit and up to 999 days after last dose of study drug ]
    Treatment-emergent AEs by SOC (all causalities) - all participants, by time. Data presented for Post Month 96 includes data up to and including Month 114.


Secondary Outcome Measures :
  1. Percent of Patients With American College of Rheumatology (ACR) 20, 50, and 70 Responses [ Time Frame: Every visit until study completion ]

    The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

    ACR20 is defined as a 20% improvement from baseline in tender/painful joint count and swollen joint count, and at least 3 of the following 5 variables: Subject's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, Subject's Assessment of Arthritis Pain, Health Assessment Questionnaire - Disability Index, C-Reactive Protein (CRP).

    ACR50 is a 50% improvement and ACR70 a 70% improvement in these variables.


  2. Area Under American College of Rheumatology (ACR) n Curve [ Time Frame: Not applicable as no data were collected for this endpoint. ]
    No data were collected for this endpoint because it was removed from the protocol in a previous amendment.

  3. Disease Activity Score (DAS)28 (C-reactive Protein [CRP]) and DAS28 (Erythrocyte Sedimentation Rate [ESR]) [ Time Frame: Every visit until study completion ]

    Descriptive statistics for DAS28-3 (CRP) and DAS28-4 (ESR). The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

    DAS28 is a composite score, calculated using a mathematical formula, and is derived from the number of tender/painful joints (out of 28), number of swollen joints (out of 28), and a blood marker of inflammation (ESR or CRP). DAS28-4 also includes a score of general health in the formula.

    The score range is from 0 to 9.4, with a higher score indicating more disease activity. A score of >5.1 indicates active disease, a score of ≤3.2 indicates low disease activity, and a score of <2.6 indicates disease remission.


  4. Number (%) of Participants With DAS28-4 (ESR) and DAS28-3 (CRP) <2.6 and ≤3.2 [ Time Frame: Every visit until study completion ]

    Percent participants with DAS28-4 (ESR) <2.6 and ≤3.2 and percent participants with DAS28-3 (CRP) <2.6 and ≤3.2. The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

    DAS28 is a composite score, calculated using a mathematical formula, and is derived from the number of tender/painful joints (out of 28), number of swollen joints (out of 28), and a blood marker of inflammation (ESR or CRP). DAS28-4 also includes a score of general health in the formula.

    The score range is from 0 to 9.4, with a higher score indicating more disease activity. A score of >5.1 indicates active disease, a score of ≤3.2 indicates low disease activity, and a score of <2.6 indicates disease remission.


  5. Health Assessment Questionnaire - Disability Index (HAQ-DI) Score [ Time Frame: Every visit until study completion ]

    Change from baseline by visit. HAQ-DI scores range from 0 to 3, where lower score implies less disease. A reduction from baseline in score indicates an improvement in condition. A clinically meaningful decrease from baseline is defined as a decrease of at least 0.22 units.

    The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.


  6. Short-Form-36 Health Survey (SF-36) Score [ Time Frame: Every visit until study completion ]
    Change from Baseline for Physical Component and Mental Component Scores by visit. SF-36 is a health status measure of 8 general health domains, each scored on a 0 to 100 scale: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. These domains can be summarized as physical and mental component scores. The domain scores were "normed" and the resulting component scores treated as Z-scores with a scale of negative to positive infinity. A higher score implies less disease. The greater the change from baseline, the greater the improvement. The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

  7. FACIT Fatigue Scale, EuroQol EQ 5D, Work Limitations Questionnaire, and RA Healthcare Resource Utilization Questionnaire (RA-HCRU) [ Time Frame: Every visit until study completion ]

    Change from Baseline Scores for each: FACIT Fatigue Scale (score range 0 to 52, higher score indicates higher quality of life and an increase from baseline score indicates improvement), EuroQol EQ 5D (index values derived from a measure of central tendency and a measure of dispersion, an increase from baseline indicates improvement, score range 0 to 1), Work Limitations (WL) Physical Demands (covers ability to perform job tasks that involve bodily strength, a decrease from baseline indicates improvement, score range 0 to 100, higher scores indicating greater limitation), and RA Healthcare Resource Utilization Work Performance in Past 3 Months on Days Bothered by RA (assesses healthcare use over previous 3 months, a decrease from baseline indicates improvement, score range 0 to 10).

    The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.


  8. Preservation of Joint Structure in Participants Who Had Baseline Radiographs Obtained in Their Qualifying Index Study [ Time Frame: Every 6 months until study completion ]

    Modified Total Sharp Score per visit. Baseline score was the last available assessment from the index study. The Modified Total Sharp Score measures disease progression; increased scores indicate disease progression. Score range 0 (normal) to 448 (worst possible total score). The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed on each occasion varied, and is provided for each visit presented.

    TSS=Total Sharp Score


  9. Vaccine Sub-study. Percent Achieving a Satisfactory Humoral Response to the Pneumococcal Vaccine as Defined by ≥ 2-fold Increase in Antibody Concentrations [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Number (%) of participants achieving a satisfactory humoral response to the pneumococcal vaccine as defined by ≥2-fold increase in antibody concentration from vaccine sub-study visit 2 (vaccination baseline) in ≥6 of 12 anti-pneumococcal antigens (serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) The number of participants was the number with a determinate antibody titer to the given vaccine antigen within the population.

    95% CI is based on Clopper-Pearson exact method for response rate.


  10. Vaccine Sub-study. Percent Achieving a Satisfactory Humoral Response to the Seasonal Influenza Vaccine as Defined by ≥ 4-fold Increase in Antibody Titers [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Number of participants achieving a satisfactory humoral response to the seasonal influenza vaccine as defined by ≥4-fold increase in antibody titers from visit 2 (vaccination baseline) in ≥2 of 3 influenza antigens (HAI B, HAI H1N1, and HAI H3N2) The number of participants was the number with a determinate antibody titer to the given vaccine antigen within the population.

    95% CI is based on Clopper-Pearson exact method for response rate.


  11. Vaccine Sub-study. Percentage of Participants Achieving Protective Antibody Titers to the Seasonal Influenza Vaccine as Measured by a Hemagglutination Inhibition (HI) Assay Titer of ≥ 1:40 in ≥ 2 of 3 Influenza Antigens at Vaccine Sub-study Visit 3 and 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Number (%) of participants achieving protective antibody titers to the seasonal influenza vaccine as measured by an HAI assay titer of ≥1:40 in ≥2 of 3 influenza antigens measured at vaccine sub-study visits 3 and 4.

    The number of participants was the number with a determinate antibody titer to the given vaccine antigen within the population.

    95% CI is based on Clopper-Pearson exact method for response rate.


  12. Vaccine Sub-study. Percentage of Participants Who Respond to Each of the 12 Pneumococcal Antigens as Defined by ≥ 2-fold Increase in Antibody Concentrations From Vaccine Sub-study Visit 2 (Vaccination Baseline) Measured at Vaccine Sub-study Visit 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Number (%) of participants achieving a satisfactory humoral response to the pneumococcal vaccine as defined by ≥2-fold increase in antibody concentration from vaccine sub-study visit 2 (vaccination baseline) in ≥6 of 12 anti-pneumococcal antigens (serotypes 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) The number of participants was the number with a determinate antibody titer to the given vaccine antigen within the population.

    95% CI is based on Clopper-Pearson exact method for response rate.


  13. Vaccine Sub-study. Percentage of Participants Who Respond to Each of the 3 Influenza Antigens as Defined by ≥ 4-fold Increase in Antibody Titers From Vaccine Sub-study Visit 2 (Vaccination Baseline) Measured at Vaccine Sub-study Visit 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Number (%) of participants achieving a satisfactory humoral response to the seasonal influenza vaccine defined as ≥4-fold increase in antibody titers from visit 2 (vaccination baseline) in ≥2 of 3 influenza antigens (HAI B, HAI H1N1, and HAI H3N2).

    The number of participants was the number with a determinate antibody titer to the given vaccine antigen within the population.

    95% CI is based on Clopper-Pearson exact method for response rate.


  14. Vaccine Sub-study. Fold Increase of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens Above Vaccination Baseline Values (Vaccine Sub-study Visit 2) at Vaccine Sub-study Visit 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Geometric Mean Fold Increase From Baseline of Pneumococcal Antigens Measured at Visit 4.

    n was the number of participants with valid and determinate assay results for the specified serotype at the given visit.

    The stated number of participants analyzed was the total number of participants. The actual number of participants analyzed for some serotypes varied, and is provided where it differed from the total number of participants.

    Confidence Intervals (CIs) were back transformations of a CI based on the Student t distribution for the mean logarithm of the concentrations.


  15. Vaccine Sub-study. Fold Increase of Anti-influenza Antibody Levels to Each of the 3 Influenza Antigens Above Vaccination Baseline Values (Vaccine Sub-study Visit 2) at Vaccine Sub-study Visit 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Geometric Mean Fold Increase From Baseline of Influenza Antigens Measured at Visit 4.

    n was the number of participants with valid and determinate assay results for the specified HAI strain at the given visit.

    Confidence Intervals (CIs) were back transformations of a CI based on the Student t distribution for the mean logarithm of the titers.


  16. Vaccine Sub-study. Concentrations of Anti-pneumococcal Antibodies at Vaccine Sub-study Visit 3 and 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]

    Mean pneumococcal concentrations (ug/mL) at vaccine baseline (visit 2) and post-vaccination visits (visits 3 and 4) by serotype. The stated number of participants analyzed was the total number of participants in each group. The actual number of participants analyzed for each serotype varied, and is provided for each individually.

    ug/mL=micrograms per milliliter


  17. Vaccine Sub-study. Titers of Anti-influenza Antibodies at Vaccine Sub-study Visit 3 and 4 [ Time Frame: From vaccine sub-study visit 2 (baseline) to sub-study visit 4 ]
    Mean influenza antibody titers at visits 3 and 4.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects who have participated in a randomized "qualifying" study of CP-690,550 for the treatment of rheumatoid arthritis

Vaccine sub-study visit

  • Subjects actively participating in Study A3921024 must have completed at least 3 months of continuous 10 mg BID CP-690,550 treatment in A3921024 as defined by >80% compliance with prescribed dose consumption of CP-690,550 over the previous 3 months.

Exclusion Criteria:

  • Serious medical conditions that would make treatment with CP-690,550 potentially unsafe

Vaccine sub-study visit

  1. Any documented influenza or pneumococcal infection within the last 3 months prior to randomization in this study
  2. Received any vaccine within 1 month prior to randomization in this study
  3. Received an influenza vaccine within 6 months or a pneumococcal vaccine within 5 years of randomization in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00413699


  Show 469 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

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

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00413699     History of Changes
Other Study ID Numbers: A3921024
2006-005035-19 ( EudraCT Number )
First Posted: December 20, 2006    Key Record Dates
Results First Posted: March 27, 2018
Last Update Posted: July 10, 2018
Last Verified: June 2018

Keywords provided by Pfizer:
long-term
open-label
safety

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action