Clinical trial NCT02087696: Uncontrolled Study to Evaluate Efficacy of Tocilizumab in Patients With Moderate or Severe Rheumatoid Arthritis
Official title: Uncontrolled Study to Evaluate Efficacy of Tocilizumab in Patients With Moderate or Severe Rheumatoid Arthritis and Candidates With a Biological Monotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Arthritis, Rheumatoid
Keywords: Arthritis, Rheumatoid
methotrexate
intolerance
poor compliance
contraindication
Tocilizumab
monotherapy
Lead sponsor: Spanish Foundation of Rheumatology
Sponsor class: OTHER
Collaborators: name: Roche Farma, S.A
First posted: 2014-03-14
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.


Eligibility 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).

Primary outcomes:
measure: Percentage of patients achieving good or moderate European League Against Rheumatism (EULAR) response.
timeFrame: At 24 weeks of treatment.
Secondary outcomes:
measure: Changes in the mean of DAS28 index.
timeFrame: Between baseline and week 24.
measure: Changes in the mean of Simplex Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI).
timeFrame: At 24 weeks of treatment.
measure: Percentage of patients complying American College of Rheumatology (ACR) criteria (ACR20, ACR50 and ACR70).
timeFrame: At 24 weeks of treatment
measure: Changes in the mean of DAS28 index into several subgroups.
timeFrame: between baseline and week 24
measure: Percentage of patients with a DAS28 index less than or equal to 3.2
timeFrame: At week 24 of treatment.
measure: Number of non-serious, serious or unexpected adverse events.
timeFrame: At the end of study (32 weeks).
measure: Changes in the mean of Health-Related Quality of Life (HRQOL) index into several subgroups.
timeFrame: between baseline and week 24.
Other outcomes:
Locations:
city: Vitoria-Gasteiz
country: Spain
facility: Hospital Universitario Araba (Sede Txagorritxu)
state: Alava
city: Orihuela
country: Spain
facility: Hospital del la Agencia Valenciana de Salud Vega Baja
state: Alicante
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Ibiza
country: Spain
facility: Hospital Can Misses
state: Islas Baleares
city: Mallorca
country: Spain
facility: Hospital Universitari Son Espases
state: Islas Baleares
city: San Cristóbal de La Laguna
country: Spain
facility: Hospital Universitario de Canarias
state: Santa Cruz de Tenerife
city: Sagunto
country: Spain
facility: Hospital de Sagunto
state: Valencia
city: Galdácano
country: Spain
facility: Hospital Galdakao-Usansolo
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d´Hebron
city: Cádiz
country: Spain
facility: Hospital Universitario Puerta del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Granada
country: Spain
facility: Hospital San Cecilio
city: Guadalajara
country: Spain
facility: Hospital Universitario de Guadalajara
city: La Coruña
country: Spain
facility: Complejo hospitalario Universitario de A Coruña
city: León
country: Spain
facility: Complejo Asistencial Universitario de León
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Málaga
country: Spain
facility: Hospital Civil
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
Study officials:
affiliation: Hospital Vall d'Hebron
name: Sara Marsal Barril, MD; PhD
role: PRINCIPAL_INVESTIGATOR
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