Uncontrolled Study to Evaluate Efficacy of Tocilizumab in Patients With Moderate or Severe Rheumatoid Arthritis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Spanish Foundation of Rheumatology
Sponsor:
Collaborator:
Roche Farma, S.A
Information provided by (Responsible Party):
Spanish Foundation of Rheumatology
ClinicalTrials.gov Identifier:
NCT02087696
First received: March 6, 2014
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

The purpose of this project is to evaluate the efficacy of Tocilizumab (TCZ) given as monotherapy in patients with active rheumatoid arthritis (RA) according to EULAR response at 24 weeks after treatment initiation.

The study design is an intervention study, uncontrolled, multicenter, prospective, 32-weeks, two cohorts of patients with poor compliance or with any contraindication or intolerance to methotrexate.

One cohort naive to previous biological therapy and the other one treated previously with a biological treatment.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Tocilizumab
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Uncontrolled Study to Evaluate Efficacy of Tocilizumab in Patients With Moderate or Severe Rheumatoid Arthritis and Candidates With a Biological Monotherapy

Resource links provided by NLM:


Further study details as provided by Spanish Foundation of Rheumatology:

Primary Outcome Measures:
  • Percentage of patients achieving good or moderate European League Against Rheumatism (EULAR) response. [ Time Frame: At 24 weeks of treatment. ] [ Designated as safety issue: No ]
    To evaluate the efficacy of Tocilizumab monotherapy administered in patients with active rheumatoid arthritis, in terms of percentage of patients achieving good or moderate European League Against Rheumatism (EULAR) response. To be classified as a good response, patients must have a clinically significant change (> 1.2) in DAS28 index as well as achieving low disease activity. Moderate answer assumes DAS28 index decreases between 0.6 and 1,2, long as it reaches low or moderate disease activity (DAS28 ≤ 5.1), or clinically significant (> 1.2) in the DAS28 in patients with a moderate or high activity (DAS28> 3.2) is achieved.


Secondary Outcome Measures:
  • Changes in the mean of DAS28 index. [ Time Frame: Between baseline and week 24. ] [ Designated as safety issue: No ]
    To evaluate the efficacy of Tocilizumab monotherapy administered in patients with active rheumatoid arthritis, in terms of Disease Activity Score 28 (DAS28) change by the response EULAR criteria.

  • Changes in the mean of Simplex Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI). [ Time Frame: At 24 weeks of treatment. ] [ Designated as safety issue: No ]
    To evaluate the activity of rheumatoid arthritis by the Simplex Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) using the mean change in these index.

  • Percentage of patients complying American College of Rheumatology (ACR) criteria (ACR20, ACR50 and ACR70). [ Time Frame: At 24 weeks of treatment ] [ Designated as safety issue: No ]
    To evaluate the efficacy by the American College of Rheumatology (ACR) criteria.

  • Changes in the mean of DAS28 index into several subgroups. [ Time Frame: between baseline and week 24 ] [ Designated as safety issue: No ]

    To evaluate the efficacy in patients with active rheumatoid arthritis treated with Tocilizumab monotherapy by the change in DAS28 index between baseline and week 24 in the following subgroups:

    Baseline DAS28: greater than 3.2 and less than 5.1 Baseline DAS28: greater than or equal to 5.1 Cohort A: Patients who have never been treated with biological therapy. Cohort B: Patients who have been previously treated with biological therapy.


  • Percentage of patients with a DAS28 index less than or equal to 3.2 [ Time Frame: At week 24 of treatment. ] [ Designated as safety issue: No ]
  • Number of non-serious, serious or unexpected adverse events. [ Time Frame: At the end of study (32 weeks). ] [ Designated as safety issue: Yes ]
    To evaluate the safety of Tocilizumab monotherapy during the study period.

  • Changes in the mean of Health-Related Quality of Life (HRQOL) index into several subgroups. [ Time Frame: between baseline and week 24. ] [ Designated as safety issue: No ]

    To evaluate the Health-Related Quality of Life (HRQOL) of patients with rheumatoid arthritis treated with Tocilizumab monotherapy in the following subgroups:

    Baseline DAS28: greater than 3.2 and less than 5.1 Baseline DAS28: greater than or equal to 5.1 Cohort A: Patients who have never been treated with biological therapy. Cohort B: Patients who have been previously treated with biological therapy.



Estimated Enrollment: 122
Study Start Date: May 2014
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Naive biological treatment

Rheumatoid arthritis patients with intolerance or poor compliance or contraindication to methotrexate and who have not received previous biological treatment.

Tocilizumab dose 8mg/kg administered every 4 weeks for 24 weeks

Drug: Tocilizumab
Tocilizumab dose 8mg/kg administered every 4 weeks during 24 weeks.
Other Name: RoActemra
Previous Biological treatment

Rheumatoid arthritis patients with intolerance or poor compliance or contraindication to methotrexate and who have not received more than two previous biological treatments.

Tocilizumab dose 8mg/kg administered every 4 weeks for 24 weeks

Drug: Tocilizumab
Tocilizumab dose 8mg/kg administered every 4 weeks during 24 weeks.
Other Name: RoActemra

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with ability and willing to provide written informed consent and comply with the requirements of the study protocol.
  • Patients with active moderate or severe rheumatoid arthritis, according to 1987 ACR criteria, diagnosed at least 6 months before inclusion.
  • 18 years old or older
  • DAS28 index greater than 3.2 at baseline.
  • If patients are receiving corticosteroid the dose will have to be ≤ 10 mg of prednisone (or equivalent) and the patient must have been stable for at least one month previous to initiating treatment with Tocilizumab (day 1). Patients may have been treated with nonsteroidal antiinflammatory drug (NSAIDs) at stable doses during the previous month to inclusion.
  • Patients receiving outpatient treatment.
  • Women of childbearing potential and men with childbearing potential partners may only participate in the study if they use reliable contraception (eg barrier methods [the patient or her partner], oral or patch contraceptives, spermicide and barrier method or intrauterine device) during the study period and at least 3 months after receiving the last dose of Tocilizumab.
  • In women of childbearing potential the pregnancy test must be negative at the screening visit and at baseline.
  • Patients on methotrexate monotherapy or combined treatment with a biological agent, or patients on biological treatment monotherapy, who show or have ever shown intolerance or poor compliance or safety issues with methotrexate.
  • Patients judge to be candidates to biological monotherapy by the researcher, without excluding previous use of other disease-modifying antirheumatic drug (DMARDs) different to methotrexate.

Exclusion Criteria:

  • Patients with no peripheral venous access.
  • Patients with previous failure to more than two biological treatments.
  • Previous treatment with Tocilizumab at any time before the baseline visit.
  • Treatment with any other agent on research during the four weeks previous to the screening visit (or equivalent period to its five half-lives) Considering the longest period.
  • Previous treatment with cell depletion therapies, including experimental treatments or approved agents, as for examples: CAMPATH, antiCD4, antiCD5, antiCD3, antiCD19 and antiCD20).
  • Treatment with intravenous gammaglobulin or plasmapheresis in the 6 months previous to the baseline visit.
  • Intra-articular or parenteral corticosteroids within 4 weeks previous to the baseline visit.
  • Immunization with a live / attenuated vaccine in the previous 4 weeks to the baseline visit.
  • Previous treatment with alkylating agents such as chlorambucil, or full lymphoid irradiation.
  • History of severe allergic or anaphylactic reactions to human, humanized or murine, monoclonal antibodies.
  • Evidence of serious uncontrolled concomitant disease: cardiovascular, nervous system, lung (including chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus) or gastrointestinal.
  • History of diverticulitis, diverticulosis requiring treatment with antibiotics, or chronic lower gastrointestinal ulcer disease, Crohn's disease, ulcerative colitis or any other lower gastrointestinal symptomatic conditions that could predispose to perforations.
  • Known active Infections, or a history of known recurring infections: Mycobacterial, fungal, viral or bacterial type (included, but not limited to, tuberculosis, atypical mycobacterial disease, hepatitis B and C, herpes zoster, but excluding nail bed fungal infections).
  • Any major episode of infection that required hospitalization or treatment with intravenous antibiotics within 4 weeks previous to the screening visit or oral antibiotics within 2 weeks previous to the screening visit.
  • Active tuberculosis requiring treatment in the past year. Latent tuberculosis screening will be perform on all patients according to Spanish Society of Rheumatology/Spanish Agency for Medicines and Health Products (SER/AEMPS) guidelines of the. Patients treated for tuberculosis without recurrence in the past 3 years will not be excluded.
  • Ongoing liver disease as determined by the principal investigator.
  • Evidence of active malignancy, malignancies diagnosed in the previous 10 years (including solid and hematologic tumors, except basal cell carcinoma and squamous cell skin or removed and cured in situ cervix carcinoma), or breast cancer diagnosed in the previous 20 years.
  • Pregnant or breastfeeding women.
  • Patients with reproductive potential who are unwilling to use effective contraception.
  • History of alcoholism, drug abuse or addiction in the previous year to the screening visit.
  • Neuropathies or other painful conditions that may interfere with pain assessment.
  • Serum creatinine >1,4 mg/dl (124 mol/l) in women and >1.6 mg/dl (141 mol/l) in men.
  • Alanine aminotransferase or aspartate aminotransferase > 1.5 times the upper limit of normal.
  • Total bilirubin greater than the upper limit of normal.
  • Platelet count minor than 100 x 10^9/l (100.000/mm3).
  • Hemoglobin minor than 85 g/L (<8,5 g/dL, 5,3 mmol/L).
  • Leukocytes minor than 3,0 x 10^9/L (3000/mm3).
  • Neutrophils, absolute value minor than 2,0 x 10^9/L (2000/mm3).
  • Lymphocytes, absolute value minor than 0,5 x 10^9 /L (500/mm3).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02087696

Contacts
Contact: María Auxiliadora Martín, MD, PhD 0034915767799 ext 273 mauxiliadora.martin@ser.es
Contact: Jesús Tomás Sánchez Costa 003466656 918 jesus.sanchez@ser.es

Locations
Spain
Hospital Universitario Araba (Sede Txagorritxu) Not yet recruiting
Vitoria-Gasteiz, Alava, Spain, 01009
Principal Investigator: Juan Carlos Vesga         
Hospital del la Agencia Valenciana de Salud Vega Baja Not yet recruiting
Orihuela, Alicante, Spain, 03314
Principal Investigator: María Isabel Tevar         
Hospital Universitari de Bellvitge Active, not recruiting
Hospitalet de Llobregat, Barcelona, Spain, 08907
Hospital Universitario Marques de Valdecilla Not yet recruiting
Santander, Cantabria, Spain, 39008
Principal Investigator: Enriqueta Peiro         
Hospital Can Misses Active, not recruiting
Ibiza, Islas Baleares, Spain, 07800
Hospital Universitari Son Espases Active, not recruiting
Mallorca, Islas Baleares, Spain, 07120
Hospital de Sagunto Not yet recruiting
Sagunto, Valencia, Spain, 46520
Principal Investigator: Antonio Gracia         
Hospital Galdakao-Usansolo Not yet recruiting
Galdácano, Vizcaya, Spain, 48960
Principal Investigator: Manuel Flores         
Hospital Universitari Vall d´Hebron Recruiting
Barcelona, Spain, 08035
Principal Investigator: Sara Marsal Barril, MD; PhD         
Hospital Universitario Reina Sofía Active, not recruiting
Córdoba, Spain, 14004
Complejo Hospitalario Regional Virgen de las Nieves Not yet recruiting
Granada, Spain, 18014
Principal Investigator: Enrique Raya Álvarez         
Hospital Universitario de Guadalajara Not yet recruiting
Guadalajara, Spain, 19002
Principal Investigator: Jesús Tornero         
Complejo hospitalario Universitario de A Coruña Recruiting
La Coruña, Spain, 15006
Principal Investigator: Francisco Blanco         
Complejo Asistencial Universitario de León Not yet recruiting
León, Spain, 24080
Principal Investigator: Trinidad Perez Sandoval         
Hospital Universitario de La Princesa Active, not recruiting
Madrid, Spain, 28006
Hospital Civil Active, not recruiting
Málaga, Spain, 29009
Hospital Clínico Universitario de Valencia Not yet recruiting
Valencia, Spain, 46010
Principal Investigator: Pilar Trenor         
Hospital Universitario Dr. Peset Not yet recruiting
Valencia, Spain, 46017
Principal Investigator: Juan José Alegre         
Sponsors and Collaborators
Spanish Foundation of Rheumatology
Roche Farma, S.A
Investigators
Principal Investigator: Sara Marsal Barril, MD; PhD Hospital Universitari Vall d´Hebron
  More Information

Publications:

Responsible Party: Spanish Foundation of Rheumatology
ClinicalTrials.gov Identifier: NCT02087696     History of Changes
Other Study ID Numbers: FER-TOC-2013-01, 2013-004051-20
Study First Received: March 6, 2014
Last Updated: August 29, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by Spanish Foundation of Rheumatology:
Arthritis, Rheumatoid
methotrexate
intolerance
poor compliance
contraindication
Tocilizumab
monotherapy

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on October 01, 2014