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Trial record 64 of 69 for:    response | "Connective Tissue Disease" | "Abatacept"

A Study Comparing Biologics + Methotrexate With Biologics + Tacrolimus in Patients With Rheumatoid Arthritis (RA)

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ClinicalTrials.gov Identifier: NCT03737708
Recruitment Status : Recruiting
First Posted : November 9, 2018
Last Update Posted : March 8, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Korea, Inc. )

Brief Summary:
The purpose of this study is to compare the efficacy of Biologics + Methotrexate with Biologics + Tacrolimus measured by the disease activity score 28 (DAS28) erythrocyte sedimentation rate (ESR) and the American College of Rheumatology (ACR) scores. The study will also assess the safety of the combinations.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis (RA) Drug: tacrolimus Drug: methotrexate Biological: adalimumab Biological: tocilizumab Biological: abatacept Phase 4

Detailed Description:
This study will include 4-weeks screening and a 12-week open-label treatment period.The participants in this study will visit the center five (5) times over the study period.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 148 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Compare Efficacy and Safety Between Biologics + Methotrexate (MTX) vs Biologics + Tacrolimus (TAC) (Switched From Biologics + Methotrexate (MTX)) in the Patients With Rheumatoid Arthritis (RA): Randomized, Interventional, Open, Active Controlled, Parallel Group, Multicenter-designed, Phase 4 Clinical Trial
Actual Study Start Date : February 13, 2019
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : February 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: tacrolimus + biologics
Participants will receive tacrolimus daily for 12 weeks. In addition, each participant will be administered one of adalimumab, tocilizumab, or abatacept for 12 weeks.
Drug: tacrolimus
Administered orally
Other Names:
  • FK506
  • Prograf

Biological: adalimumab
Administered as subcutaneous injection

Biological: tocilizumab
Administered by intravenous injection

Biological: abatacept
Administered by intravenous injection

Active Comparator: methotrexate + biologics
Participants will receive methotrexate weekly for 12 weeks. In addition, each participant will be administered one of adalimumab, tocilizumab, or abatacept for 12 weeks.
Drug: methotrexate
Administered orally

Biological: adalimumab
Administered as subcutaneous injection

Biological: tocilizumab
Administered by intravenous injection

Biological: abatacept
Administered by intravenous injection




Primary Outcome Measures :
  1. Change in disease activity score 28 (DAS28) erythrocyte sedimentation rate score (ESR) score at 12 weeks [ Time Frame: From baseline (week 1) to week 12 ]

    DAS28-ESR will be calculated using data from tender joint count (TJC) (28 joints), swollen joint count (SJC) (28 joints), ESR and Subject's Global Assessment of Arthritis (SGA) with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA.

    High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.



Secondary Outcome Measures :
  1. Disease activity score 28 (DAS28) erythrocyte sedimentation rate (ESR) rate score at 4 weeks [ Time Frame: At 4 weeks ]

    DAS28-ESR will be calculated using data from TJC (28 joints), SJC (28 joints), ESR and SGA with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA.

    High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.


  2. DAS28 (ESR) score at 8 weeks [ Time Frame: At 8 weeks ]

    DAS28-ESR will be calculated using data from TJC (28 joints), SJC (28 joints), ESR and SGA with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA.

    High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.


  3. DAS28 (ESR) score at 12 weeks [ Time Frame: At 12 weeks ]

    DAS28-ESR will be calculated using data from TJC (28 joints), SJC (28 joints), ESR and SGA with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA.

    High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.


  4. Change in DAS28 (ESR) score at 4 weeks [ Time Frame: From baseline (week 1) to week 4 ]

    DAS28-ESR will be calculated using data from TJC (28 joints), SJC (28 joints), ESR and SGA with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA.

    High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.


  5. Change in DAS28 (ESR) score at 8 weeks [ Time Frame: From baseline (week 1) to week 8 ]

    DAS28-ESR will be calculated using data from TJC (28 joints), SJC (28 joints), ESR and SGA with the formula; DAS28- ESR = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 x SGA.

    High disease activity: DAS28 score exceeding 5.1 Moderate disease activity: DAS28 score of exceeding 3.2 to 5.1 Low disease activity: DAS28 score of less than or equal to 3.2 If the DAS28 score is less than 2.6, the participant will be considered to be in DAS28 remission.


  6. ACR 20 response rate [ Time Frame: At 12 weeks ]
    Percent of participants with American College of Rheumatology (ACR) 20 response rate The ACR20 response requires that all criteria from (1) to (3) be met compared with Week 0 (baseline); (1), Tender Joint Count (TJC) >= 20% reduction; (2), Swollen Joint Count (SJC) >= 20% reduction;(3) >= 20% improvement in three or more of the following five parameters - [1] subject's assessment of pain, [2] Subject's Global Assessment of Arthritis (SGA), [3] Physician's Global Assessment of Arthritis (PGA), [4] health assessment questionnaire-disability index (HAQ-DI), [5] acute phase reactant (erythrocyte sedimentation rate (ESR)).

  7. ACR50 response rate [ Time Frame: At 12 weeks ]
    Percent of participants with ACR50 response rate The ACR50 response indicates a 50% improvement in all criteria used in the ACR20 assessment.

  8. ACR70 response rate [ Time Frame: At 12 weeks ]
    Percent of participants with ACR70 response rate The ACR70 response indicates a 70% improvement in all criteria used in the ACR70 assessment.

  9. Safety assessed by Adverse Events (AEs) [ Time Frame: Up to 16 weeks ]
    An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product.

  10. Safety assessed by incidence of serious adverse events (SAE) [ Time Frame: Up to 16 weeks ]
    Adverse Event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.

  11. Safety assessed by incidence of treatment emergent adverse events (TEAE) [ Time Frame: Up to 12 weeks ]
    Treatment Emergent Adverse Event (TEAE) is defined as any AE which starts, or worsens, after the first dose of study drug through 30 days after the last dose of study drug.

  12. Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 16 weeks ]
    Number of participants with potentially clinically significant laboratory values.

  13. Number of participants with vital sign abnormalities and /or adverse events (AEs) [ Time Frame: Up to 16 weeks ]
    Number of participants with potentially clinically significant vital sign values.

  14. Number of participants with physical exam abnormalities and/or adverse events (AEs) [ Time Frame: Up to 16 weeks ]
    Number of participants with potentially clinically significant physical exam values.



Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with rheumatoid arthritis (RA) diagnosed by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR).
  • Subjects who have been treated with combination therapy of one of biologic agent (adalimumab, tocilizumab, or abatacept) + methotrexate (MTX) over 2 months prior to Visit 1.
  • Disease Activity Score (DAS28) erythrocyte sedimentation rate (ESR) ≥ 3.2 at screening and baseline.
  • Subject agrees not to participate in another interventional study while participating in the present study.

Exclusion Criteria:

  • Subjects with a past history of allergic reaction to Investigational Product or Comparative Drug used in this study.
  • Subjects who were given tacrolimus (TAC) within three months before participation in this study.
  • Subjects who have been treated with combination therapy of one of biologic agent (adalimumab, tocilizumab, or abatacept) + MTX exceeds 3 months at Baseline.
  • Subjects who were already taking 20 mg of MTX at Screening Period.
  • Subjects who were given the prohibited concomitant medications prior to randomization.
  • Subjects with a medical history of clinically significant blood, gastrointestinal, endocrine, lung, nerve, or brain diseases at screening.
  • Subjects with a medical history of clinically significant liver, kidney, or heart diseases:

    • Liver disease: Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT) > 3 × upper limit of normal (ULN) at screening, viral infection, nonviral infection, and liver cirrhosis;
    • Kidney disease: serum creatinine > 2.0 mg/dL at screening;
    • Heart disease: heart failure of ≥ The New York Heart Association class 3, arrhythmia or ischemic heart disease requiring treatment, and QTc interval > 450 ms on Electrocardiogram (ECG) at screening;
  • Subjects with a history of uncontrolled diabetes (glycosylated hemoglobin > 8.5%).
  • Subjects with hyperkalemia or serum potassium level > ULN of site reference ranges at screening.
  • Subjects with severe respiratory disease or chronic generalized infectious disease.
  • Subject who have a history of chronic infection or severe or life-threatening infection within 24 weeks before the baseline visit.
  • Subject who are known to be infected by Human Immunodeficiency Virus, Hepatitis B, or Hepatitis C.
  • Subject has a history of active tuberculosis or latent tuberculosis infection without treatment.
  • Subject with mental disorder uncontrolled by drugs.
  • Subject with chronic diarrhea, ulcerative stomatitis, gastric ulcer, or ulcerative colitis.
  • Subject with genetic disorders including galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
  • Subject with maculopathy, retinal disorders, or clinically significant eye diseases that may lead to visual disorder.
  • Subject with bone marrow disorder, leukopenia, and blood cell disorder such as severe anemia and thrombocytopenia.
  • Subject with a history of major surgery within 12-weeks before screening.
  • Subject who were diagnosed with malignant tumors within 5 years before screening or who need treatment for malignant tumors diagnosed in the past.
  • Patients with basal cell and squamous cell carcinomas of the skin or carcinoma in situ of the cervix uteri that has been excised and cured, may be included on the study at the discretion of the investigator.
  • Female subject who is positive for the serum pregnancy test at Visit 1 among a woman of childbearing potential (WOCBP) (menopausal is defined as amenorrhea for at least one year) or not surgically sterile, or is not willing to use appropriate contraception during the study. Female subject trying to become pregnant or is currently pregnant or breast feeding.
  • Male subject who donates sperm during the treatment period and for at least 30 days whichever is longer after the final study drug administration.
  • Male subject with a pregnant or breastfeeding partner(s) who do not agree to remain abstinent or use a condom for the duration of the pregnancy, or for the time partner is breastfeeding, throughout the study period and for 30 days whichever is longer after the final study drug administration.

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): NCT03737708


Contacts
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Contact: Astellas Pharma Korea, Inc +82 2 3448 0504 astellas.registration@astellas.com

Locations
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Korea, Republic of
Site KR82004 Recruiting
Busan, Korea, Republic of
Site KR82003 Recruiting
Daegu, Korea, Republic of
Site KR82007 Recruiting
Daegu, Korea, Republic of
Site KR82006 Recruiting
Daejeon, Korea, Republic of
Site KR82011 Recruiting
Gwangju, Korea, Republic of
Site KR82002 Recruiting
Incheon, Korea, Republic of
Site KR82014 Recruiting
Jeonju, Korea, Republic of
Site KR82009 Recruiting
Seongnam, Korea, Republic of
Site KR82001 Recruiting
Seoul, Korea, Republic of
Site KR82005 Recruiting
Seoul, Korea, Republic of
Site KR82008 Recruiting
Seoul, Korea, Republic of
Site KR82012 Recruiting
Seoul, Korea, Republic of
Site KR82013 Recruiting
Suwon, Korea, Republic of
Sponsors and Collaborators
Astellas Pharma Korea, Inc.
Investigators
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Study Director: Medical Monitor Astellas Pharma Korea, Inc.

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Responsible Party: Astellas Pharma Korea, Inc.
ClinicalTrials.gov Identifier: NCT03737708     History of Changes
Other Study ID Numbers: 506-MA-3187
First Posted: November 9, 2018    Key Record Dates
Last Update Posted: March 8, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Korea, Inc. ):
tacrolimus
abatacept
Prograf
adalimumab
methotrexate
tocilizumab
FK506
Additional relevant MeSH terms:
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Connective Tissue Diseases
Abatacept
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Autoimmune Diseases
Immune System Diseases
Adalimumab
Methotrexate
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Calcineurin Inhibitors
Anti-Inflammatory Agents