GRC-TCL-2010-01

Fundación Instituto de Investigación Sanitaria de Santiago de Compostela

Travesía da Choupana s/n, Santiago de Compostela, Spain,

Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, ma.teresa.cabaleiro.ocampo@sergas.es

Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, ma.teresa.cabaleiro.ocampo@sergas.es

No

No

No

Final

26 Sep 2016

Yes

27 Oct 2015

Yes

27 Oct 2015

No

- To evaluate the efficacy of the administration of tocilizumab, in patients with OT of moderate to the threat of vision in active phase (according to the EUGOGO guidelines); With little or no response to glucocorticoid pulses. - To observe the safety of the drug tocilizumab in these patients.

Patients who during the visits of the study are detected laboratory values of liver function, neutrophil count and platelet count outside of normal parameters a dose adjustment should be made. In case of a severe hypersensitivity reaction medication should be available for the treatment of hypersensitivity reactions for immediate use. These Medications include antihistamines, corticosteroids and adrenaline. If there is any sign or symptom of a possible reaction to the infusion, and the state cardiovascular remains stable: the infusion rate and the time of infusion should be lengthened; If the patient continues to show signs and symptoms of hypersensitivity, a dose of antihistamines should be administered via intramuscular or slow intravenous In patients who experience severe reactions to the infusion with a collapse cardiovascular disease, the infusion should be interrupted and the patient should be treated as if it was an anaphylactic reaction with intravenous antihistamines, corticosteroids and adrenaline, if necessary. No more medication will be administered study and the patient will be definitively removed from it.

01 Jul 2013

No

No

Spain: 32

32

32

0

0

0

0

0

0

30

2

0

Baseline period

Randomised - controlled

Pharmacists at the participant centers prepared tocilizumab in a sterile and pyrogen-free solution of 0.9% sodium chloride as well as a similar placebo solution, but the pharmacists were masked to the participants. Participants, people giving the interventions, those assessing outcomes, and those analyzing the data were masked to group assignment. There were no cases of unmasking throughout the entire masking process.

Yes

Placebo

Solution for injection

Intravenous use

The placebo to be used is a pyrogen-free sterile solution of sodium chloride at 0.9% with a final volume of 100 mL, administered once every four weeks over the total sixteen-week period. The placebo will be prepared only insofar as necessary to mask its nature before its administration

TOCILIZUMAB

Solution for injection

Intravenous use

The dosage of Tocilizumab is 8 mg/Kg of body weight, concentrate in solution for intravenous injection (each ml of concentrate contains 20 mg of Tocilizumab), and administered once every four weeks over a 16-week period. Once the Tocilizumab dosage has been adjusted for the patient’s weight, the weight-appropriate volume of Tocilizumab is to substitute the same volume of solution in a 100 mL infusion bag, with the final volume always 100 mL. IMP should be administered at approximately the same time (four-hour margin), preferably in the morning and on the same day of the week (three-day margin).

Week 16

Randomised - controlled

Pharmacists at the participant centers prepared tocilizumab in a sterile and pyrogen-free solution of 0.9% sodium chloride as well as a similar placebo solution, but the pharmacists were masked to the participants. Participants, people giving the interventions, those assessing outcomes, and those analyzing the data were masked to group assignment. There were no cases of unmasking throughout the entire masking process.

Yes

Placebo

Solution for injection

Intravenous use

The placebo to be used is a pyrogen-free sterile solution of sodium chloride at 0.9% with a final volume of 100 mL, administered once every four weeks over the total sixteen-week period. The placebo will be prepared only insofar as necessary to mask its nature before its administration

TOCILIZUMAB

Solution for injection

Intravenous use

The dosage of Tocilizumab is 8 mg/Kg of body weight, concentrate in solution for intravenous injection (each ml of concentrate contains 20 mg of Tocilizumab), and administered once every four weeks over a 16-week period. Once the Tocilizumab dosage has been adjusted for the patient’s weight, the weight-appropriate volume of Tocilizumab is to substitute the same volume of solution in a 100 mL infusion bag, with the final volume always 100 mL. IMP should be administered at approximately the same time (four-hour margin), preferably in the morning and on the same day of the week (three-day margin).

TOCILIZUMAB

Solution for injection

Intravenous use

The dosage of Tocilizumab is 8 mg/Kg of body weight, concentrate in solution for intravenous injection (each ml of concentrate contains 20 mg of Tocilizumab), and administered once every four weeks over a 16-week period. Once the Tocilizumab dosage has been adjusted for the patient’s weight, the weight-appropriate volume of Tocilizumab is to substitute the same volume of solution in a 100 mL infusion bag, with the final volume always 100 mL. IMP should be administered at approximately the same time (four-hour margin), preferably in the morning and on the same day of the week (three-day margin).

Week 40

Randomised - controlled

Yes

Placebo

Solution for injection

Intravenous use

The placebo to be used is a pyrogen-free sterile solution of sodium chloride at 0.9% with a final volume of 100 mL, administered once every four weeks over the total sixteen-week period. The placebo will be prepared only insofar as necessary to mask its nature before its administration

TOCILIZUMAB

Solution for injection

Intravenous use

The dosage of Tocilizumab is 8 mg/Kg of body weight, concentrate in solution for intravenous injection (each ml of concentrate contains 20 mg of Tocilizumab), and administered once every four weeks over a 16-week period. Once the Tocilizumab dosage has been adjusted for the patient’s weight, the weight-appropriate volume of Tocilizumab is to substitute the same volume of solution in a 100 mL infusion bag, with the final volume always 100 mL. IMP should be administered at approximately the same time (four-hour margin), preferably in the morning and on the same day of the week (three-day margin).

Control

Intervention

Control

Intervention

Control

Intervention

Control

Intervention

The efficacy of the administration of the medicine Tocilizumab will be measured as an improvement in the disorder, stated as a reduction in the CAS (clinical activity score) of 2 or m more points on a scale of 10. This will be measured on every visit and compared before treatment (week - 4/0), with after treatment (week 16) and after completion of the follow-up period (week 40). Exploratory analyses of other variables of secondary outcomes may be undertaken. The activity of the disease will be measured using a clinical activity score (CAS). CAS is based on well-known classic clinical signs, such as pain, reddening, oedema and ocular dysfunction. CAS consists of 10 items and a point is assigned for each item, all of them are of equal importance and the final score is obtained by adding up all the points for the 10 items. The final score will be between 0 and 10. A clinical activity score of ≥ 4 indicates that the GO is in the active phase.

Primary

Proportion of patients with improvements in CAS by at least 2 at week 16 and at week 40.

The ITT population included all randomized patients who received at least 1 infusion of the study treatment.Fisher test analyzed categorical variables, and nonparametric tests compared changes from baseline in levels of anti-TPO,anti-TG,TSH,TSI,SF-36, and GOQoL. OR estimation was used to measure the effect size.Last observation was carried forward when a data point was missing. Patients discontinuing the study were imputed as nonresponders. A 2-sided<.05 was considered the limit of significance

Control v Intervention

32

Pre-specified

Secondary

Week 16

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Secondary

Week 16 and week 40

Percentage (confidence interval) of Patients With No Worsening in the Components of the Clinical Activity Score

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

Post-hoc

Week 16 and week 40

0AA / pregnancies were collected as soon as the patient signs the Informed Consent until 30 days after the patient's last visit. Study Information about AAs that have been produced between the previous visit and the current visit were requested.

2002

Control - week 16

Intervention - week 16

Control - week 40

Internvention - week 40