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Arthritis, RheumatoidPhase 4NCT02087696

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

A Phase 4 study testing Tocilizumab in people with Arthritis, Rheumatoid, run by Spanish Foundation of Rheumatology at 20 sites in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Arthritis, Rheumatoid
What is being tested?
Tocilizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
122 participants
Where
20 sitesSpain
Study dates
May 2014to Jul 2016
Phase
Phase 4
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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).

Trial locations and contacts

20 sites in 1 country.

María Auxiliadora Martín, MD, PhD contact

0034915767799 ext. 273

mauxiliadora.martin@ser.es

Jesús Tomás Sánchez Costa contact

003466656 918

jesus.sanchez@ser.es

20 sites in 1 country

Spain20 sites, 12 recruiting

  • Complejo hospitalario Universitario de A Coruña

    A Coruña, La Coruña, 15006

    Francisco Blanco

    Recruiting

  • Hospital Universitari Vall d´Hebron

    Barcelona, Barcelona, 08035

    Sara Marsal Barril, MD; PhD

    Recruiting

  • Hospital Universitario Puerta del Mar

    Cadiz, Cádiz, 11009

    Active, not recruiting

  • Hospital Universitario Reina Sofía

    Córdoba, Córdoba, 14004

    Eduardo Collantes

    Recruiting

  • Hospital Galdakao-Usansolo

    Galdakao, Vizcaya, 48960

    Active, not recruiting

  • Hospital San Cecilio

    Granada, Granada, 18012

    Enrique Raya

    Recruiting

  • Hospital Universitario de Guadalajara

    Guadalajara, Guadalajara, 19002

    Active, not recruiting

  • Hospital Can Misses

    Ibiza Town, Balearic Islands, 07800

    Ana Urruticoechea

    Recruiting

  • Hospital Universitari de Bellvitge

    L'Hospitalet de Llobregat, Barcelona, 08907

    Active, not recruiting

  • Complejo Asistencial Universitario de León

    León, León, 24080

    Active, not recruiting

  • Hospital Universitario de La Princesa

    Madrid, Madrid, 28006

    Rosario García de Vicuña

    Recruiting

  • Hospital Civil

    Málaga, Málaga, 29009

    María Ángeles Belmonte, MD

    Recruiting

  • Hospital Universitari Son Espases

    Mallorca, Balearic Islands, 07120

    Active, not recruiting

  • Hospital del la Agencia Valenciana de Salud Vega Baja

    Orihuela, Alicante, 03314

    María Isabel Tevar

    Recruiting

  • Hospital de Sagunto

    Sagunto, Valencia, 46520

    Antonio Gracia

    Recruiting

  • Hospital Universitario de Canarias

    San Cristóbal de La Laguna, Santa Cruz de Tenerife, 38320

    Sagrario Bustabad

    Recruiting

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

    Active, not recruiting

  • Hospital Clínico Universitario de Valencia

    Valencia, Valencia, 46010

    Pilar Trenor

    Recruiting

  • Hospital Universitario Dr. Peset

    Valencia, Valencia, 46017

    Juan José Alegre

    Recruiting

  • Hospital Universitario Araba (Sede Txagorritxu)

    Vitoria-Gasteiz, Alava, 01009

    Active, not recruiting

Other trials in Spain

About this study

Official title: Uncontrolled Study to Evaluate Efficacy of Tocilizumab in Patients With Moderate or Severe Rheumatoid Arthritis and Candidates With a Biological Monotherapy

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.

Being tested
Tocilizumab
Keywords
Arthritis, Rheumatoid, methotrexate, intolerance, poor compliance, contraindication, Tocilizumab, monotherapy
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TocilizumabDrug

    Also called RoActemra

    Tocilizumab dose 8mg/kg administered every 4 weeks during 24 weeks.

Study groups in NCT02087696
Study groupRoleWhat they receive
Naive biological treatmentOtherRheumatoid 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
Receives: Drug: Tocilizumab
Previous Biological treatmentOtherRheumatoid 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
Receives: Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of patients achieving good or moderate European League Against Rheumatism (EULAR) response.

    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.

    Measured: At 24 weeks of treatment.

Secondary outcomes (7)

  1. Changes in the mean of DAS28 index.

    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.

    Measured: Between baseline and week 24.

  2. Changes in the mean of Simplex Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI).

    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.

    Measured: At 24 weeks of treatment.

  3. Percentage of patients complying American College of Rheumatology (ACR) criteria (ACR20, ACR50 and ACR70).

    To evaluate the efficacy by the American College of Rheumatology (ACR) criteria.

    Measured: At 24 weeks of treatment

  4. Changes in the mean of DAS28 index into several subgroups.

    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.

    Measured: between baseline and week 24

  5. Percentage of patients with a DAS28 index less than or equal to 3.2

    Measured: At week 24 of treatment.

  6. Number of non-serious, serious or unexpected adverse events.

    To evaluate the safety of Tocilizumab monotherapy during the study period.

    Measured: At the end of study (32 weeks).

  7. Changes in the mean of Health-Related Quality of Life (HRQOL) index into several subgroups.

    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.

    Measured: between baseline and week 24.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2014 (estimated)
  2. Study startMay 2014
  3. Primary completionDec 2015 (estimated)
  4. Study completionJul 2016 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
122 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02087696
Sponsor's protocol ID
FER-TOC-2013-01
Other IDs
2013-004051-20
Status last verified
May 2015
First submitted
6 Mar 2014
Last updated
22 May 2015
Results posted
No
Data monitoring committee
No

Publications

  • Carmona L, Villaverde V, Hernandez-Garcia C, Ballina J, Gabriel R, Laffon A; EPISER Study Group. The prevalence of rheumatoid arthritis in the general population of Spain. Rheumatology (Oxford). 2002 Jan;41(1):88-95. doi: 10.1093/rheumatology/41.1.88.

    PubMed 11792885

  • Lajas C, Abasolo L, Bellajdel B, Hernandez-Garcia C, Carmona L, Vargas E, Lazaro P, Jover JA. Costs and predictors of costs in rheumatoid arthritis: a prevalence-based study. Arthritis Rheum. 2003 Feb 15;49(1):64-70. doi: 10.1002/art.10905.

    PubMed 12579595

  • Carmona L, Ballina J, Gabriel R, Laffon A; EPISER Study Group. The burden of musculoskeletal diseases in the general population of Spain: results from a national survey. Ann Rheum Dis. 2001 Nov;60(11):1040-5. doi: 10.1136/ard.60.11.1040.

    PubMed 11602475

  • Smolen JS, Landewe R, Breedveld FC, Dougados M, Emery P, Gaujoux-Viala C, Gorter S, Knevel R, Nam J, Schoels M, Aletaha D, Buch M, Gossec L, Huizinga T, Bijlsma JW, Burmester G, Combe B, Cutolo M, Gabay C, Gomez-Reino J, Kouloumas M, Kvien TK, Martin-Mola E, McInnes I, Pavelka K, van Riel P, Scholte M, Scott DL, Sokka T, Valesini G, van Vollenhoven R, Winthrop KL, Wong J, Zink A, van der Heijde D. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2010 Jun;69(6):964-75. doi: 10.1136/ard.2009.126532. Epub 2010 May 5.

    PubMed 20444750

  • Knevel R, Schoels M, Huizinga TW, Aletaha D, Burmester GR, Combe B, Landewe RB, Smolen JS, Sokka T, van der Heijde DM. Current evidence for a strategic approach to the management of rheumatoid arthritis with disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of rheumatoid arthritis. Ann Rheum Dis. 2010 Jun;69(6):987-94. doi: 10.1136/ard.2009.126748. Epub 2010 May 6.

    PubMed 20448280

  • Eberhardt K, Fex E. Clinical course and remission rate in patients with early rheumatoid arthritis: relationship to outcome after 5 years. Br J Rheumatol. 1998 Dec;37(12):1324-9. doi: 10.1093/rheumatology/37.12.1324.

    PubMed 9973158

  • Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum. 2005 Nov;52(11):3381-90. doi: 10.1002/art.21405.

    PubMed 16258899

  • Aletaha D, Stamm T, Kapral T, Eberl G, Grisar J, Machold KP, Smolen JS. Survival and effectiveness of leflunomide compared with methotrexate and sulfasalazine in rheumatoid arthritis: a matched observational study. Ann Rheum Dis. 2003 Oct;62(10):944-51. doi: 10.1136/ard.62.10.944.

    PubMed 12972472

  • De La Mata J, Blanco FJ, Gomez-Reino JJ. Survival analysis of disease modifying antirheumatic drugs in Spanish rheumatoid arthritis patients. Ann Rheum Dis. 1995 Nov;54(11):881-5. doi: 10.1136/ard.54.11.881.

    PubMed 7492236

  • Galindo-Rodriguez G, Avina-Zubieta JA, Russell AS, Suarez-Almazor ME. Disappointing longterm results with disease modifying antirheumatic drugs. A practice based study. J Rheumatol. 1999 Nov;26(11):2337-43.

    PubMed 10555887

  • Grove ML, Hassell AB, Hay EM, Shadforth MF. Adverse reactions to disease-modifying anti-rheumatic drugs in clinical practice. QJM. 2001 Jun;94(6):309-19. doi: 10.1093/qjmed/94.6.309.

    PubMed 11391029

  • Fitzpatrick R, Scott DG, Keary I. Cost-minimisation analysis of subcutaneous methotrexate versus biologic therapy for the treatment of patients with rheumatoid arthritis who have had an insufficient response or intolerance to oral methotrexate. Clin Rheumatol. 2013 Nov;32(11):1605-12. doi: 10.1007/s10067-013-2318-z. Epub 2013 Jul 9.

    PubMed 23835658

  • DiMatteo MR. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004 Mar;42(3):200-9. doi: 10.1097/01.mlr.0000114908.90348.f9.

    PubMed 15076819

  • van den Bemt BJ, Zwikker HE, van den Ende CH. Medication adherence in patients with rheumatoid arthritis: a critical appraisal of the existing literature. Expert Rev Clin Immunol. 2012 May;8(4):337-51. doi: 10.1586/eci.12.23.

    PubMed 22607180

  • Waimann CA, Marengo MF, de Achaval S, Cox VL, Garcia-Gonzalez A, Reveille JD, Richardson MN, Suarez-Almazor ME. Electronic monitoring of oral therapies in ethnically diverse and economically disadvantaged patients with rheumatoid arthritis: consequences of low adherence. Arthritis Rheum. 2013 Jun;65(6):1421-9. doi: 10.1002/art.37917.

    PubMed 23728826

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Tocilizumab in people with Arthritis, Rheumatoid, run by Spanish Foundation of Rheumatology at 20 sites in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 May 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact María Auxiliadora Martín, MD, PhD (0034915767799 ext. 273, mauxiliadora.martin@ser.es), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of patients achieving good or moderate European League Against Rheumatism (EULAR) response. (time frame: At 24 weeks of treatment.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02087696, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2015.

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