A Long-Term Extension Study of WA22762 to Evaluate Safety and Efficacy of Subcutaneous Tocilizumab in Participants With Moderate to Severe Rheumatoid Arthritis (RA).

NCT01734993 | Completed Phase 3 Results

• 1 other identifier: ML28544
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 6

Brief Summary

This multicenter, open-label, single arm, interventional, long-term extension (LTE) study will evaluate the safety and efficacy of tocilizumab (TCZ, RoActemra/Actemra) in French participants with moderate to severe RA who have completed the Week 97 visit of WA22762 LTE study (NCT01194414) (EudraCT Number 2010-018375-22). Participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in disease activity score based on 28-joint count \[DAS28\] of greater than \[\>\] 1.2 points) will continue TCZ treatment within this local LTE study for a maximum of 156 weeks of subcutaneous (SC) TCZ treatment, or until SC TCZ becomes commercially available, whichever occurs first.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (8)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a study treatment regardless of whether or not the event has a causal relationship with the treatment. An AE, therefore, could be any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study treatment, whether or not related to the treatment. A SAE was any untoward medical occurrence that at any dose resulted in death, was life threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity, and congenital anomaly/birth defect. AEs included SAEs as well as non-serious AEs.

  Baseline up to approximately 142 weeks

• Percentage of Participants With AEs and SAEs Related to TCZ

  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included SAEs as well as non-serious AEs. Causality of AEs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on drug cessation \[DC\], relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs). AEs with causality of certain, probable/likely, and possible were considered TCZ related.

  Baseline up to approximately 142 weeks

• Percentage of Participants With Adverse Events of Special Interest (AESIs)

  Adverse events of special interest (AESI) for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events.

  Baseline up to approximately 142 weeks

• Percentage of Participants With AESIs Related to TCZ

  AESI for this study included: infections (including opportunistic infections), myocardial infarction/acute coronary syndrome, gastrointestinal perforation and related events, malignancies, anaphylaxis / hypersensitivity reactions, demyelinating disorders, stroke, bleeding events and hepatic events. Percentage of participants with AESI related to the drug were presented. Causality of AESIs based on physician's discretion: certain (AE after drug intake, not explained by other drugs, reaction on DC, relapse on re-intake of drug), probable/likely (AE after drug intake, not explained by other drugs, reaction on DC, no information on re-intake), possible (AE after drug intake, explained by other drugs, no information on DC), unlikely (not related to drug intake time, explained by other drugs). AESIs with causality of certain, probable/likely, and possible were considered TCZ related.

  Baseline up to approximately 142 weeks

• Percentage of Participants With AEs Leading to TCZ Discontinuation, Interruption, or Dose Modification

  An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Percentage of participants with AE causing drug discontinuation, interruption and increase or decrease in dose of drug was presented.

  Baseline up to approximately 142 weeks

• Percentage of Participants With Clinically Significant Physical Examinations and Vital Signs Abnormalities

  Criteria for potentially clinically important (PCI) change in vital signs: heart rate value of less than (\<) 40 beats per minute and value greater than (\>) 150 beats per minute, systolic blood pressure (SBP) of \< 80 or \>210 millimeter of mercury (mmHg), diastolic blood pressure (DBP) of \<40 or \>130 mmHg, body temperature \<32 or \> 40 degrees Celsius, respiratory rate of \<10 or \> 50 breaths/minute and criteria for PCI change in physical examination: \>/=10% increase or decrease of body weight in kilograms (kg).

  Baseline up to approximately 142 weeks

• Percentage of Participants With Clinically Significant Laboratory Abnormalities

  Criteria for laboratory tests clinically significant abnormalities included: hemoglobin, hematocrit and red blood cells (RBCs)(\< 0.8\*lower limit of normal\[LLN\]); leucocytes (\<0.6/greater than \[\>\]1.5\*upper limit of normal \[ULN\]); platelets (\<0.5\*LLN\>\</0\>1.75\*ULN); neutrophils, lymphocytes (\<0.8\*LLN\>\</0\>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin, direct bilirubin, indirect bilirubin (\>1.5\*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (\>3\*ULN), total protein, albumin (\<0.8\*LLN\>\</0\>1.2\*ULN); creatinine, urea (\>1.3\*ULN); glucose (\<0.6\*LLN\>\</0\>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN\>\</0\>1.1\*ULN); urine RBCs, urine white blood cells (WBCs) (\> or equal\[=\]20 high-powered field), urine bacteria \>20 high-powered field. Overall percentage of participants with any clinically significant laboratory abnormality was reported.

  Baseline up to approximately 142 weeks

• Percentage of Participants With Anti-TCZ Antibodies

  Baseline up to approximately 142 weeks

Secondary Outcomes (15)

• Change From Baseline in Disease Activity Score 28 - Erythrocyte Sedimentation Rate (DAS28-ESR) Score

  Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)

• Change From Baseline in Simplified Disease Activity Index (SDAI) Score

  Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)

• Change From Baseline in TJC

  Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)

• Change From Baseline in SJC

  Baseline (Day 0), Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, completer last visit (up to Week 120), last visit (up to Week 120), early withdrawal (up to Week 120)

• Percentage of Participants With Clinical Remission

  Week 48, 108

Study Arms (1)

Tocilizumab

EXPERIMENTAL

Moderate to severe rheumatoid arthritis participants from France, who completed the Week 97 visit of the WA22762 LTE study and considered as responders (defined as having improvement in DAS28 of \>1.2 points) will continue tocilizumab treatment within this local LTE study for a maximum of 156 weeks, or until SC TCZ becomes commercially available, whichever occurs first.

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

Participants will receive TCZ 162 milligrams (mg) SC injection once a week.

Also known as: RoActemra, Actemra

Tocilizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Negative pregnancy test at screening and baseline
• Participants who have completed the 97-week WA22762 LTE study on SC or intravenous (IV) TCZ and who experienced, at any time during WA22762, clinically significant improvement in DAS28 (\>1.2 points), and based on the investigator's judgment may continue to benefit from TCZ treatment in this study investigating the SC formulation
• No current or recent adverse events or laboratory findings preventing the use of the study drug dose of TCZ 162 mg SC at baseline visit
• Receiving treatment on an outpatient basis
• Females of childbearing potential and males with female partners of childbearing potential must agree to use reliable means of contraception during the study and for at least 3 months following the last dose of study drug
• Oral corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDS) up to the recommended dose are permitted if on stable dose regimen for greater than and equal to (\>/=) 4 weeks prior to baseline
• Permitted non-biological disease-modifying anti-rheumatic drugs (DMARDs) are allowed

You may not qualify if:

• Participants who have prematurely withdrawn from the WA22762 LTE study for any reason
• Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies
• Treatment with an anti-tumor necrosis factor (TNF) or anti-interleukin (IL) 1 agent, or a T-cell co stimulation modulator since the last administration of study drug in the WA22762 LTE study
• Immunization with a live/attenuated vaccine since the last administration of study drug in the WA22762 LTE study
• Diagnosis, since last WA22762 visit (Week 97), of rheumatic autoimmune disease other than rheumatoid arthritis; secondary Sjörgen's syndrome with RA is permitted
• Diagnosis, since last WA22762 visit (Week 97), of inflammatory joint disease other than RA
• Uncontrolled disease states, such as asthma or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids
• Evidence of serious uncontrolled concomitant disease
• Known active current or history of recurrent infection
• Primary or secondary immunodeficiency (history of or currently active)
• Body weight \>150 kilograms (kg)
• Pregnant or lactating women
• Inadequate hematologic, renal or liver function
• History of alcohol, drug or chemical abuse within 1 year prior to screening

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (6)

Unknown Facility

Bordeaux, 33076, France

Location

Unknown Facility

Montpellier, 34295, France

Location

Unknown Facility

Nantes, 44035, France

Location

Unknown Facility

Paris, 75679, France

Location

Unknown Facility

Strasbourg, 67098, France

Location

Unknown Facility

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 28, 2012
• Study Start: October 1, 2012
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: November 28, 2016
• Results First Posted: November 28, 2016

Record last verified: 2016-10

Locations

FR (6)