Trial Outcomes & Findings for Study Evaluating Etanercept in Subjects With Ankylosing Spondylitis in Spain (NCT NCT00873730)

NCT ID: NCT00873730

Last Updated: 2010-04-28

Results Overview

ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement (vs. baseline) and an absolute change ≥ 10 units on a 0-100 scale (0=no disease activity; 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 108 participants
• Primary outcome timeframe: 12 weeks
• Results posted on: 2010-04-28

Participant Flow

Patients were recruited in Spain from December 2006 to February 2008.

Patients were screened up to 6 weeks.

Participant milestones

Measure	Etanercept BIW etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Overall Study STARTED	54	54
Overall Study COMPLETED	48	49
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Measure	Etanercept BIW etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Overall Study Protocol Deviation	5	2
Overall Study Adverse Event	0	2
Overall Study Withdrawal by Subject	0	1
Overall Study Sponsor decision	1	0

Baseline Characteristics

Study Evaluating Etanercept in Subjects With Ankylosing Spondylitis in Spain

Baseline characteristics by cohort

Measure	Etanercept BIW n=54 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=54 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks	Total n=108 Participants Total of all reporting groups
Age Continuous	40.22 years STANDARD_DEVIATION 10.36 • n=5 Participants	42.63 years STANDARD_DEVIATION 10.66 • n=7 Participants	41.43 years STANDARD_DEVIATION 10.53 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Sex: Female, Male Male	43 Participants n=5 Participants	43 Participants n=7 Participants	86 Participants n=5 Participants

PRIMARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 20 = 20% improvement (vs. baseline) and an absolute change ≥ 10 units on a 0-100 scale (0=no disease activity; 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 20.	34 patients	37 patients

SECONDARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 40 = 40% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (0=no disease activity, 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 40.	25 patients	25 patients

SECONDARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 50 = 50% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (0=no disease activity, 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 50.	22 patients	24 patients

SECONDARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

ASAS measures symptomatic improvement in Ankylosing Spondylitis (AS) patients. ASAS = 4 domains: patient global assessment of disease activity, pain, function, inflammation. ASAS 70 = 70% improvement (vs. baseline) and an absolute change ≥ 20 units on a 0-100 scale (0=no disease activity, 100=high disease activity) for ≥ 3 domains, and no worsening in remaining domain.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 70.	15 patients	20 patients

SECONDARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

ASAS 5/6 consists of 6 domains: the 4 used in ASAS 20 (patient global assessment of disease activity, pain, function, inflammation measured on a 0-100 scale, where 0=no disease activity, 100=high disease activity) plus spinal mobility and an acute phase reactant, C Reactive Protein (CRP). Achieving ASAS 5/6 requires a 20% improvement compared to baseline in ≥ 5 domains and no worsening in the remaining domain.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Number of Patients Achieving Assessment in Ankylosing Spondylitis (ASAS) 5/6.	20 patients	22 patients

SECONDARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

Partial remission defined as a score of less than 20 units (on a scale of 0-100, where 0=no disease activity, 100=high disease activity) in each of the 4 Assessment in Ankylosing Spondylitis (ASAS) domains: patient global assessment of disease activity, pain, function, and inflammation. For scale, 100=high disease activity.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Number of Patients Achieving Partial Remission.	14 patients	13 patients

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population.

Nocturnal back and overall spinal pain assessed by patients using a Visual Analog Scale (VAS) of 0 - 10 (0 = no pain and 10 = most severe pain).

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in Nocturnal Back and Overall Spinal Pain From Baseline to Week 12. Nocturnal Back Pain	-3.96 units on scale Standard Deviation 3.15	-4.15 units on scale Standard Deviation 2.76
Change in Nocturnal Back and Overall Spinal Pain From Baseline to Week 12. Overall Spinal Pain	-3.89 units on scale Standard Deviation 2.99	-3.53 units on scale Standard Deviation 2.85

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population.

Patient pain assessed by physician and patient using a Visual Analog Scale (VAS) of 0 - 10 (0 = none and 10 = severe).

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in Physician and Patient Global Assessment (PGA) of Pain From Baseline to Week 12. Physician Global Assessment	-4.15 units on scale Standard Deviation 1.77	-4.12 units on scale Standard Deviation 1.39
Change in Physician and Patient Global Assessment (PGA) of Pain From Baseline to Week 12. Patient Global Assessment	-3.67 units on scale Standard Deviation 3.13	-4.17 units on scale Standard Deviation 2.69

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population.

BASFI is a validated self assessment tool that determines the degree of functional limitation in AS patients. Utilizing a VAS of 0-10 (0=easy, 10=impossible), patients answered 10 questions assessing their ability in completing normal daily activities or physically demanding activities. The BASFI score is a mean score of the 10 questions.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in Bath Ankylosing Spondylitis Functional Index (BASFI) From Baseline to Week 12.	-2.61 units on scale Standard Deviation 2.64	-2.45 units on scale Standard Deviation 2.12

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population.

BASDAI is a validated self assessment tool used to determine disease activity in patients with Ankylosing Spondylitis (AS). Utilizing a Visual Analog Scale (VAS) of 0-10 (0=none and 10=very severe) patient's answered 6 questions measuring discomfort, pain and fatigue. The BASDAI final mean score was calculated taking all 6 VAS assessments.

Outcome measures

Measure	Etanercept BIW n=48 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) From Baseline to Week 12.	-3.67 units on scale Standard Deviation 2.18	-3.59 units on scale Standard Deviation 2.46

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population.

BASMI is an objective measure of spinal mobility. The BASMI score is composed of 5 measures: cervical rotation, intermalleolar distance, modified Schober's test, lateral flexion and tragus to wall distance. Each measure was scored 0-2 (0=normal mobility, 2=severe reduction) to give a final score ranging 0 to 10.

Outcome measures

Measure	Etanercept BIW n=46 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=45 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in Bath Ankylosing Spondylitis Metrology Index (BASMI) From Baseline to Week 12.	-0.46 units on scale Standard Deviation 0.98	-0.80 units on scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population.

ESR is a laboratory test that provides a non-specific measure of inflammation. The test assesses the rate at which red blood cells fall in a test tube and is measured in mm/hour. Normal range is 0-30mm/h. A higher rate is consistent with inflammation.

Outcome measures

Measure	Etanercept BIW n=47 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=46 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in Erythrocyte Sedimentation Rate (ESR) From Baseline to Week 12.	-11.8 mm/hour Standard Deviation 14.47	-16.2 mm/hour Standard Deviation 16.06

SECONDARY outcome

Timeframe: 12 weeks

Population: The analysis population was the intent to treat population.

EuroQol questionnaire is intended to measure the quality of life by means of questions about mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Answers to every question were grouped in two main categories: with problems (having some problems or absolutely unable) or without problems.

Outcome measures

Measure	Etanercept BIW n=47 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Mobility Without Problems	37 patients	33 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Mobility With Problems	10 patients	16 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Self-care Without Problems	29 patients	29 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Self-care With Problems	18 patients	20 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Usual activities Without Problems	20 patients	17 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Usual activities With Problems	27 patients	32 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Pain/Discomfort Without Problems	5 patients	13 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Pain/Discomfort With Problems	42 patients	36 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Anxiety/Depression Without Problems	28 patients	32 patients
Ankylosing Spondylitis Quality of Life (EuroQoL) Questionnaire Anxiety/Depression With Problems	19 patients	17 patients

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population was the intent to treat population. Two scored areas had a different "Number of Participants Analyzed" in the etanercept arm. Bodily pain had 45 and Emotional role limitations had 46.

SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

Outcome measures

Measure	Etanercept BIW n=47 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=49 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Physical functioning	15.53 units on scale Standard Deviation 27.73	19.90 units on scale Standard Deviation 20.73
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Physical role limitations	30.32 units on scale Standard Deviation 50.79	32.14 units on scale Standard Deviation 42.08
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Bodily pain	-1.39 units on scale Standard Deviation 22.31	-1.43 units on scale Standard Deviation 24.02
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. General health	7.23 units on scale Standard Deviation 13.22	9.59 units on scale Standard Deviation 12.11
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Vitality	8.65 units on scale Standard Deviation 13.61	12.14 units on scale Standard Deviation 14.58
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Social functioning	8.24 units on scale Standard Deviation 16.75	6.12 units on scale Standard Deviation 20.59
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Emotional role limitations	17.39 units on scale Standard Deviation 42.01	17.01 units on scale Standard Deviation 40.89
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline to Week 12. Mental health	7.34 units on scale Standard Deviation 11.53	6.27 units on scale Standard Deviation 11.02

SECONDARY outcome

Timeframe: 12 weeks

Population: The population for this assessment was patients who had ocular inflammatory disease at baseline. The number of patients analyzed is zero because no patients had symptoms of ocular inflammatory disease at baseline.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Population: The analysis population is the intent to treat.

CRP is a marker of inflammation and measured in mg/l. A higher level is consistent with inflammation.

Outcome measures

Measure	Etanercept BIW n=45 Participants etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW n=44 Participants etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Change in C-reactive Protein (CRP) From Baseline to Week 12.	-11.6 mg/l Standard Deviation 18.42	-11.7 mg/l Standard Deviation 21.44

Adverse Events

Etanercept BIW

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

Etanercept QW

Serious events: 2 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Etanercept BIW etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
Gastrointestinal disorders Diarrheic syndrome	0.00% 0/54	1.9% 1/54
Gastrointestinal disorders Diarrhea	1.9% 1/54	0.00% 0/54
Respiratory, thoracic and mediastinal disorders Viral respiratory infection	0.00% 0/54	1.9% 1/54

Other adverse events

Measure	Etanercept BIW etanercept 50 mg twice a week (BIW) for 12 weeks	Etanercept QW etanercept 50 mg once a week (QW) and placebo once a week for 12 weeks
General disorders Injection site reaction	13.0% 7/54	14.8% 8/54
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	9.3% 5/54	14.8% 8/54
Respiratory, thoracic and mediastinal disorders Pharyngitis	0.00% 0/54	3.7% 2/54
Gastrointestinal disorders Abdominal pain	3.7% 2/54	0.00% 0/54
Gastrointestinal disorders Diarrhea	1.9% 1/54	3.7% 2/54
Investigations Transaminases increased	7.4% 4/54	7.4% 4/54
Injury, poisoning and procedural complications Procedural dizziness	1.9% 1/54	3.7% 2/54
Nervous system disorders Dizziness	3.7% 2/54	0.00% 0/54

Additional Information

U. S. Contact Center

Wyeth

Email: clintrialresults@wyeth.com

Results disclosure agreements

• Principal investigator is a sponsor employee The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.
• Publication restrictions are in place

Restriction type: OTHER