Trial Outcomes & Findings for RESTART C0168Z05 Rheumatoid Arthritis Study (NCT NCT00714493)

Last Updated: 2013-09-12

Results Overview

Percent of patients who achieved EULAR response at Week 10. EULAR response is defined based on the DAS28 score and the EULAR response criteria (Van Gestel et al, 1996 and 1999). At a given visit, patients with a DAS28 score of ≤ 5.1 are considered EULAR responders if the improvement from baseline in their DAS28 score is greater than 0.6; Or patients with a DAS28 score \> 5.1 are considered EULAR responders if the improvement from baseline in their DAS28 score is \> 1.2.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

203 participants

Primary outcome timeframe

Week 10

Results posted on

2013-09-12

Participant Flow

Participant milestones

Participant milestones
Measure	Infliximab Infliximab 3 mg/kg (intravenously) at weeks 0,2,6; Increase to 5 mg/kg (i.v.) or 7 mg/kg (i.v.) based on EULAR response
Overall Study STARTED	203
Overall Study COMPLETED	154
Overall Study NOT COMPLETED	49

Reasons for withdrawal

Reasons for withdrawal
Measure	Infliximab Infliximab 3 mg/kg (intravenously) at weeks 0,2,6; Increase to 5 mg/kg (i.v.) or 7 mg/kg (i.v.) based on EULAR response
Overall Study Adverse Event	11
Overall Study Death	3
Overall Study Lack of Efficacy	10
Overall Study Lost to Follow-up	3
Overall Study Protocol Violation	12
Overall Study SUBJECT CHOICE (SUBJECT WITHDREW CONSENT	8
Overall Study OTHER	2

Baseline Characteristics

RESTART C0168Z05 Rheumatoid Arthritis Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Infliximab n=203 Participants Infliximab 3 mg/kg (intravenously) at weeks 0,2,6; Increase to 5 mg/kg (i.v.) or 7 mg/kg (i.v.) based on EULAR response
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	171 Participants n=5 Participants
Age, Categorical >=65 years	32 Participants n=5 Participants
Age Continuous	54 years STANDARD_DEVIATION 12.07 • n=5 Participants
Sex: Female, Male Female	161 Participants n=5 Participants
Sex: Female, Male Male	42 Participants n=5 Participants
Region of Enrollment Europe	43 participants n=5 Participants
Region of Enrollment North America	160 participants n=5 Participants

PRIMARY outcome

Timeframe: Week 10

Population: The evaluable population was the subset of the mITT population (included the enrolled patients who received at least 1 dose of study medication) after excluding all 6 patients from Site 8631 where significant trial misconducts were identified.

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=197 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Percent of Patients Who Achieved a EULAR (The European League Against Rheumatism) Response at Week 10	49.7 Percentage Interval 42.6 to 56.9

SECONDARY outcome

Timeframe: Week 26

Percent of patients who achieved EULAR response at Week 10 and maintained through Week 26 without infliximab dose increase

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=197 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Percent of Patients Who Acheived EULAR Response at Week 10 and Maintained Through Week 26 Without Infliximab Dose Increase	22.3 percentage Interval 16.7 to 28.8

SECONDARY outcome

Timeframe: Week 26

Percent of patients who achieved EULAR response at Week 26, regardless of EULAR response status at Weeks 10, 14, and 22, with or without dose increase prior to Week 26

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=197 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Percent of Patients Who Achieved EULAR Response at Week 26, Regardless of EULAR Response Status at Weeks 10, 14, and 22, With or Without Dose Increase Prior to Week 26	51.8 percentage Interval 44.6 to 58.9

SECONDARY outcome

Timeframe: Week 10

Change from baseline in physical function (HAQ) at Week 10. HAQ assesses the degree of difficulty a person has in accomplishing tasks. A lower HAQ score indicates less difficulty. Change from baseline is computed as Week 10 value minus baseline value. A negative value in change from baseline indicates an improvement.

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=173 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Change From Baseline in Physical Function (HAQ)	-0.173 scale -3 to 3 Standard Deviation 0.4548

SECONDARY outcome

Timeframe: Week 26

Change from baseline in physical function (HAQ) at Week 26. HAQ assesses the degree of difficulty a person has in accomplishing tasks. A lower HAQ score indicates less difficulty. Change from baseline is computed as Week 26 value minus baseline value. A negative value in change from baseline indicates an improvement.

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=151 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Change From Baseline in Physical Function (HAQ)	-0.223 scale -3 to 3 Standard Deviation 0.4968

SECONDARY outcome

Timeframe: Week 10

Percent of patients who achieved ACR20 at Week 10. A patient is considered achieving ACR20 if the following two conditions are met: 1) An improvement of ≥ 20% from baseline in both the swollen joint count (66 joints) and tender joint count (68 joints; 2) An improvement of ≥ 20% from baseline in at least 3 of the following 5 assessments:Patient's assessment of pain visual analog scale (VAS), Patient's global assessment of disease activity (VAS), Evaluator's global assessment of disease activity (VAS), Patient's assessment of physical function as measured by the HAQ disability index, and CRP.

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=197 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Percent of Patients Who Achieved ACR20 at Week 10	28.4 percentage Interval 22.2 to 35.3

SECONDARY outcome

Timeframe: Week 26

Percent of patients who achieved ACR20 at Weeks 26. A patient is considered achieving ACR20 if the following two conditions are met: 1) An improvement of ≥ 20% from baseline in both the swollen joint count (66 joints) and tender joint count (68 joints; 2) An improvement of ≥ 20% from baseline in at least 3 of the following 5 assessments:Patient's assessment of pain visual analog scale (VAS), Patient's global assessment of disease activity (VAS), Evaluator's global assessment of disease activity (VAS), Patient's assessment of physical function as measured by the HAQ disability index, and CRP.

Outcome measures

Outcome measures
Measure	Infliximab 3 mg/kg n=197 Participants Infliximab 3 mg/kg at week 0,2,6; Increase to 5mg/kg or 7 mg/kg based on EULAR response
Percent of Patients Who Achieved ACR20 at Weeks 26.	35.5 percentage Interval 28.9 to 42.7

Adverse Events

Infliximab

Serious events: 10 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Infliximab n=203 participants at risk Infliximab 3 mg/kg (intravenously) at weeks 0,2,6; Increase to 5 mg/kg (i.v.) or 7 mg/kg (i.v.) based on EULAR response
Cardiac disorders Cardiac Failure Congestive	0.99% 2/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Acute Myocardial Infarction	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Atrial Fibrillation	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Atrioventricular Block Complete	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Cardiac Failure	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Cardiogenic Shock	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Congestive Cardiomyopathy	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Cardiac disorders Myocardial Infarction	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Blood and lymphatic system disorders Anaemia	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
General disorders Multi-Organ Failure	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Immune system disorders Hypersensitivity	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Infections and infestations Erysipelas	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Metabolism and nutrition disorders Diabetes Mellitus	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Musculoskeletal and connective tissue disorders Rheumatoid Arthritis	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic Neoplasm	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Psychiatric disorders Completed Suicide	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	0.49% 1/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.

Other adverse events

Other adverse events
Measure	Infliximab n=203 participants at risk Infliximab 3 mg/kg (intravenously) at weeks 0,2,6; Increase to 5 mg/kg (i.v.) or 7 mg/kg (i.v.) based on EULAR response
Infections and infestations Sinusitis	8.4% 17/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Infections and infestations Upper Respiratory Tract Infection	6.9% 14/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Respiratory, thoracic and mediastinal disorders Cough	5.9% 12/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Gastrointestinal disorders Nausea	5.4% 11/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.
Nervous system disorders Headache	5.4% 11/203 • All untoward events occurring between the time of obtaining informed consent through Week 30 or early termination were collected, regardless of causality.

Additional Information

Sr. Director, Clinical Research - Medical Affairs

Centocor Ortho Biotech, Inc.

Phone: 215-325-6811

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60