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The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.
The purpose of this study is to compare the effectivness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis. To demonstrate that sarilumab treatment will be effective for inducing and maintaining glucocorticoid-free remission in male or female patients with biopsy proven active, glucocorticoid-dependent sarcoidosis affecting the lungs, lymph nodes, liver, kidneys, spleen, bone, soft tissues, skin, and/or eyes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-Label Sarilumab (pre-randomization) | Experimental | On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks. |
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| Double-Blind Sarilumab (post-randomization) | Experimental | After completing the open-label period, participants are randomized in blinded fashion to receive sarilumab every two weeks for 12 weeks. |
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| Double-Blind Placebo (post-randomization) | Placebo Comparator | After completing the open-label period, participants are randomized in blinded fashion to receive placebo every two weeks for 12 weeks. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sarilumab | Drug | Sarilumab 200 mg administered subcutaneously |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) | The primary outcome was flare-free survival of sarilumab-treated patients compared to placebo-treated controls. Patients will be considered to have flared if they receive rescue medication including increased glucocorticoids, or if they discontinue the study treatment in order to start a different therapy. | Week 16 to Week 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | FVC is a pulmonary function test, and is defined as the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition. | Baseline and week 16 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Matthew Baker, MD | Stanford University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University | Palo Alto | California | 94304 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37471590 | Derived | Baker MC, Horomanski A, Wang Y, Liu Y, Parsafar S, Fairchild R, Mooney JJ, Raj R, Witteles R, Genovese MC. A double-blind, placebo-controlled, randomized withdrawal trial of sarilumab for the treatment of glucocorticoid-dependent sarcoidosis. Rheumatology (Oxford). 2024 May 2;63(5):1297-1304. doi: 10.1093/rheumatology/kead373. |
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Sixteen participants were screened, fifteen met eligibility criteria and were allocated to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Open-Label Sarilumab (Pre-randomization) | On entering the study, all participants receive open-label sarilumab (200 mg administered subcutaneously) every two weeks for 16 weeks. |
| FG001 | Double-Blind Sarilumab (Post-randomization) | After completing the open-label period, participants are randomized to receive sarilumab (200 mg administered subcutaneously) every two weeks for 12 weeks. |
| FG002 | Double-Blind Placebo (Post-randomization) | After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Open-Label Period |
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| Randomized-Withdrawal Period |
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | Participants who enter the study, to receive open-label sarilumab every two weeks for 16 weeks. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) | The primary outcome was flare-free survival of sarilumab-treated patients compared to placebo-treated controls. Patients will be considered to have flared if they receive rescue medication including increased glucocorticoids, or if they discontinue the study treatment in order to start a different therapy. | Assessed in participants in the randomized-withdrawal period | Posted | Count of Participants | Participants | Week 16 to Week 28 |
|
Up to 28 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Open-Label Sarilumab (Pre-randomization) | On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| COVID-19 | Infections and infestations | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Transaminitis | Investigations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Matthew C. Baker, Principal Investigator | Stanford University, School of Medicine, Immunology & Rheumatology | 650- 498-4528 | mbake13@stanford.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | May 19, 2020 | Aug 11, 2023 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D012507 | Sarcoidosis |
| ID | Term |
|---|---|
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006968 | Hypersensitivity, Delayed |
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| ID | Term |
|---|---|
| C000592401 | sarilumab |
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All subjects will all receive sarilumab 200 mg subcutaneously every two weeks for the first 16 weeks of the study. At Week 16, those patients who were able to successfully taper off of prednisone will then be assigned randomly to receive either sarilumab 200 mg subcutaneously every two weeks (study drug) or placebo subcutaneously for an additional 12 weeks.
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Study doctor and personnel will not know whether you are assigned to the sarilumab group or the placebo group after Week 16.
| Placebo | Drug | Placebo administered subcutaneously |
|
| Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% predicted is defined as DLCO% of the patient divided by the average DLCO% in the population for any person of similar age, sex and body composition. | Baseline, and week 16 |
| Change in Pulmonary Function (FEV1) Percent Predicted | FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. | Baseline and week 16 |
| Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Physician and patient assessments assessed using the extrapulmonary physician organ severity tool (ePOST). Score Description: 0: Not affected
| Baseline, week 16, and week 28 |
| Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Physician rates patient's disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state. | Baseline, week 16, and week 28 |
| Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Patient rates their disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state. | Baseline, week 16, and week 28 |
| Change From Baseline in FACIT-F Score (Fatigue Scale) | FACIT-F score Total score range: 0-52, lower scores correspond with more fatigue. | Baseline, week 16, and week 28 |
| Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | The 66/68 Joint Count evaluates 68 joints for tenderness and pain with movement and 66 joints for swelling (hip joints can be evaluated for tenderness only, not for swelling. Joint evaluation score: 0: Absent 1: Present 9: Not applicable | Baseline, week 16, and week 28 |
| Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Sarcoidosis Activity and Severity Index evaluates 7 parameters on a 0 to 4 scale, summed for an overall scale score of 0 to 28 (higher values indicate higher activity/severity). | Baseline, week 16, and week 28 |
| Change in Size of Sarcoidosis Lesions | Baseline, week 16, and week 28 |
| Change From Baseline in Serum Angiotensin Converting Enzyme | ACE is a serum marker that is increased in sarcoidosis. ACE is produced by epithelioid cells that are derived from recently-activated macrophages in granulomas; thus, ACE is an appropriate representative of whole-body granuloma. | Baseline, week 16, and week 28 |
| Change From Baseline in Serum C-Reactive Protein (CRP) | CRP is a protein made by the liver. The level of CRP increases when there's inflammation in the body. | Baseline, week 16, and week 28 |
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | ESR is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. | Baseline, week 16, and week 28 |
| Change in Prednisone Dose | Baseline, week 16, and week 28 |
| Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Normal range as calculated by the local laboratory. | Baseline, week 16, and week 28 |
| Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Normal range as calculated by the local laboratory. | Baseline, week 16, and week 28 |
| Number of Participants With Serum Creatinine Outside Normal Range | Normal range as calculated by the local laboratory. | Baseline, week 16, and week 28 |
| Number of Participants With Urine Protein Outside Normal Range | Normal range as calculated by the local laboratory. | Baseline, week 16, and week 28 |
| COMPLETED |
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| NOT COMPLETED |
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| years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
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After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks. |
|
|
| Secondary | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | FVC is a pulmonary function test, and is defined as the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | FVC % predicted | Baseline and week 16 |
|
|
|
| Secondary | Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% predicted is defined as DLCO% of the patient divided by the average DLCO% in the population for any person of similar age, sex and body composition. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | DLCO % predicted | Baseline, and week 16 |
|
|
|
| Secondary | Change in Pulmonary Function (FEV1) Percent Predicted | FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. | Data were collected during the open-label portion of the study only | Posted | Mean | Standard Deviation | FEV1 % predicted | Baseline and week 16 |
|
|
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| Secondary | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Physician and patient assessments assessed using the extrapulmonary physician organ severity tool (ePOST). Score Description: 0: Not affected
| Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 16, and week 28 |
|
|
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| Secondary | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Physician rates patient's disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | units on a scale (mm) | Baseline, week 16, and week 28 |
|
|
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| Secondary | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Patient rates their disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | units on a scale (mm) | Baseline, week 16, and week 28 |
|
|
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| Secondary | Change From Baseline in FACIT-F Score (Fatigue Scale) | FACIT-F score Total score range: 0-52, lower scores correspond with more fatigue. | Participants with available data at each respective time point are included in the analysis. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 16, and week 28 |
|
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| Secondary | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | The 66/68 Joint Count evaluates 68 joints for tenderness and pain with movement and 66 joints for swelling (hip joints can be evaluated for tenderness only, not for swelling. Joint evaluation score: 0: Absent 1: Present 9: Not applicable | Participants who presented with inflammatory arthritis and with available data at each respective time point are included in the analysis. | Posted | Number | joints | Baseline, week 16, and week 28 |
|
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| Secondary | Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Sarcoidosis Activity and Severity Index evaluates 7 parameters on a 0 to 4 scale, summed for an overall scale score of 0 to 28 (higher values indicate higher activity/severity). | Participants who presented with cutaneous sarcoidosis and with available data at each respective time point. | Posted | Mean | Standard Deviation | score on a scale | Baseline, week 16, and week 28 |
|
|
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| Secondary | Change in Size of Sarcoidosis Lesions | Data were not collected for this outcome | Posted | Baseline, week 16, and week 28 |
|
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| Secondary | Change From Baseline in Serum Angiotensin Converting Enzyme | ACE is a serum marker that is increased in sarcoidosis. ACE is produced by epithelioid cells that are derived from recently-activated macrophages in granulomas; thus, ACE is an appropriate representative of whole-body granuloma. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | U/L | Baseline, week 16, and week 28 |
|
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| Secondary | Change From Baseline in Serum C-Reactive Protein (CRP) | CRP is a protein made by the liver. The level of CRP increases when there's inflammation in the body. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | mg/dL | Baseline, week 16, and week 28 |
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| Secondary | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | ESR is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. | Participants with available data at each respective time point are included in the analysis | Posted | Mean | Standard Deviation | cells per hour | Baseline, week 16, and week 28 |
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| Secondary | Change in Prednisone Dose | Data were not collected for this outcome | Posted | Baseline, week 16, and week 28 |
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| Secondary | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Normal range as calculated by the local laboratory. | Participants with available data at each respective time point are included in the analysis | Posted | Count of Participants | Participants | Baseline, week 16, and week 28 |
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| Secondary | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Normal range as calculated by the local laboratory. | Participants with available data at each respective time point are included in the analysis | Posted | Count of Participants | Participants | Baseline, week 16, and week 28 |
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| Secondary | Number of Participants With Serum Creatinine Outside Normal Range | Normal range as calculated by the local laboratory. | Participants with available data at each respective time point are included in the analysis | Posted | Count of Participants | Participants | Baseline, week 16, and week 28 |
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| Secondary | Number of Participants With Urine Protein Outside Normal Range | Normal range as calculated by the local laboratory. | Participants with available data at each respective time point are included in the analysis | Posted | Count of Participants | Participants | Baseline, week 16, and week 28 |
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| 0 |
| 15 |
| 1 |
| 15 |
| 9 |
| 15 |
| EG001 | Double-Blind Sarilumab (Post-randomization) | After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks. | 0 | 2 | 0 | 2 | 1 | 2 |
| EG002 | Double-Blind Placebo (Post-randomization) | After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks. | 0 | 8 | 0 | 8 | 5 | 8 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Prolonged neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
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| Anemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Herpes zoster | Infections and infestations | Systematic Assessment |
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| Ulcers aphthous oral | Gastrointestinal disorders | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Peripheral vision defective | Eye disorders | Systematic Assessment |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Cervical radiculopathy | Reproductive system and breast disorders | Systematic Assessment |
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| Kappa light chain analysis increased | Investigations | Systematic Assessment |
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| Herniated disc | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Creatinine kinase increased | Investigations | Systematic Assessment |
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| Hyperbilirubinemia | Blood and lymphatic system disorders | Systematic Assessment |
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| Pain in (r) hip | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Alcohol rehabilitation | Psychiatric disorders | Systematic Assessment |
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| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| Change at week 16 |
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| Change at week 16 |
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| Change at week 16 |
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| Change at week 28 |
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| Change at week 16 |
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| Change at week 28 |
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| Change at week 16 |
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| Change at week 28 |
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| Change at Week 16 |
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| Change at Week 28 |
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| Baseline - swollen joints |
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| Week 16 - tender joints |
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| Week 16 - swollen joints |
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| Week 28 - tender joints |
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| Week 28 - swollen joints |
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| Week 16 |
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| Week 28 |
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| Change at week 16 |
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| Change at week 28 |
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| Change at week 16 |
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| Change at week 28 |
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| Change at week 16 |
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| Change at week 28 |
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| Week 16 |
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| Week 28 |
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| Week 16 |
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| Week 28 |
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| Week 16 |
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| Week 28 |
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| Week 16 |
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| Week 28 |
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