Sarcoidosis
Conditions
Keywords
glucocorticoid-dependent
Brief summary
The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.
Detailed description
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.
Interventions
DRUGSarilumab
Sarilumab 200 mg administered subcutaneously
DRUGPlacebo
Placebo administered subcutaneously
Sponsors
Stanford University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Study doctor and personnel will not know whether you are assigned to the sarilumab group or the placebo group after Week 16.
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Biopsy proven non-caseating granulomas consistent with sarcoidosis * negative infectious studies including AFB and fungal stains, and with compatible clinical and/or radiographic manifestations of sarcoidosis. * Involvement of the lungs (stage II or III pulmonary sarcoidosis), lymph nodes, liver, kidneys, spleen, bone, soft tissues, skin, and/or eyes. * At least one active manifestation, defined by the need for ongoing glucocorticoid treatment to control a sign or symptom of sarcoidosis, which requires treatment with prednisone (or equivalent corticosteroid) ≥ 10 mg and ≤ 60 mg daily (i.e. glucocorticoid dependence), with stable dosing for ≥ 28 days prior to baseline. * patients taking a glucocorticoid other than prednisone, will be changed to prednisone at the equivalent dose and take this daily for ≥ 14 days prior to baseline. * DMARDs including methotrexate, leflunomide, azathioprine, mycophenolate mofetil, and/or anti-malarials (i.e. hydroxychloroquine) permitted must be stable for ≥ 28 days prior to baseline and remain stable during follow-up.
Exclusion criteria
* Stage IV pulmonary sarcoidosis. * Central nervous system sarcoidosis. * Cardiac sarcoidosis. * Prior treatment with an anti-IL-6 therapy. * Treatment with a biologic agent including rituximab, belimumab, TNF inhibitors, abatacept, or IL-17 inhibitors administered within 28 days prior to baseline (6 months for rituximab). * Treatment with cyclophosphamide within 3 months prior to baseline. * Treatment with prednisone \< 10 mg or \> 60 mg daily. * Known hypersensitivity or allergy to the study drug. * History of, or current, inflammatory or autoimmune disease other than sarcoidosis which would present a safety issue or confound interpretation of the data. * Prior or current history of other significant concomitant illness that, according to the investigator's judgment, would adversely affect the patient's participation in the study. These include, but are not limited to, cardiovascular (including stage III or IV cardiac failure according to the New York Heart Association classification), neurological (including demyelinating disease), active infectious diseases, or history of diverticulitis or gastrointestinal perforation. * Patients currently pregnant or breast-feeding. * Women of childbearing potential (WOCBP) who are unwilling to utilize adequate contraception and unwilling to not become pregnant during the full course of the study (must be willing to be tested for pregnancy). Adequate contraceptive measures include oral contraceptives (continuous use, as per prescription, for 2 or more cycles prior to screening), intrauterine devices, contraceptive sponges, condoms or diaphragms plus foam, or jelly, or surgical procedures such as bilateral tubal ligation or vasectomy in partner. * Administration of a live/attenuated vaccine within 30 days. * Evidence of active tuberculosis, HIV, or hepatitis B or C infection. * History of cancer other than non-melanoma skin cancer. * Patients with any of the following laboratory abnormalities at the screening visit: hemoglobin \<8.5 g/dL, white blood cells \<3000/mm3, neutrophils \<2000/mm3, platelet count \<150,000 cells/mm3, aspartate aminotransferase (AST) or ALT \>1.5 x ULN, and/or bilirubin (total) above the upper limit of normal (unless Gilbert's disease has been determined by genetic testing and documented). * Presence of severe uncontrolled hypercholesterolemia (\>350 mg/dL, 9.1 mmol/L) or hypertriglyceridemia (\>500 mg/dL, 5.6 mmol/L) at screening or baseline. * Patients with calculated creatinine clearance \<30 mL/minute (using Cockroft-Gault formula). * History of alcohol or drug abuse within 5 years prior to the screening visit. * Participation in any clinical research study evaluating another investigational drug or therapy within 5 half-lives or 60 days of first investigational medicinal product (IMP) administration, whichever is longer. * Any patient who has had surgery within 4 weeks prior to the screening visit or with planned surgery during the course of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) | Week 16 to Week 28 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | Baseline, and week 16 | 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. |
| Change in Pulmonary Function (FEV1) Percent Predicted | Baseline and week 16 | FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height. |
| Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Baseline, week 16, and week 28 | Physician and patient assessments assessed using the extrapulmonary physician organ severity tool (ePOST). Score Description: 0: Not affected 1. Slight 2. Mild 3. Moderate 4. Moderate to severe 5. Severe 6. Very Severe 17 organ domains were rated and summed to create a total score (range 0-102, higher scores correspond with more severity). |
| Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Baseline, week 16, and week 28 | Physician rates patient's disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state. |
| Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Baseline, week 16, and week 28 | Patient rates their disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state. |
| Change From Baseline in FACIT-F Score (Fatigue Scale) | Baseline, week 16, and week 28 | FACIT-F score Total score range: 0-52, lower scores correspond with more fatigue. |
| Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Baseline, week 16, and week 28 | 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 |
| Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Baseline, week 16, and week 28 | 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). |
| Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Baseline and week 16 | 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. |
| Change From Baseline in Serum Angiotensin Converting Enzyme | Baseline, week 16, and week 28 | 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. |
| Change From Baseline in Serum C-Reactive Protein (CRP) | Baseline, week 16, and week 28 | CRP is a protein made by the liver. The level of CRP increases when there's inflammation in the body. |
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline, week 16, and week 28 | ESR is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour. |
| Change in Prednisone Dose | Baseline, week 16, and week 28 | — |
| Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Baseline, week 16, and week 28 | Normal range as calculated by the local laboratory. |
| Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Baseline, week 16, and week 28 | Normal range as calculated by the local laboratory. |
| Number of Participants With Serum Creatinine Outside Normal Range | Baseline, week 16, and week 28 | Normal range as calculated by the local laboratory. |
| Number of Participants With Urine Protein Outside Normal Range | Baseline, week 16, and week 28 | Normal range as calculated by the local laboratory. |
| Change in Size of Sarcoidosis Lesions | Baseline, week 16, and week 28 | — |
Countries
United States
Participant flow
Pre-assignment details
Sixteen participants were screened, fifteen met eligibility criteria and were allocated to treatment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Participants who enter the study, to receive open-label sarilumab every two weeks for 16 weeks. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-Label Period | Adverse Event | 1 | 0 | 0 |
| Open-Label Period | Lack of Efficacy | 4 | 0 | 0 |
| Randomized-Withdrawal Period | Adverse Event | 0 | 1 | 2 |
| Randomized-Withdrawal Period | Lack of Efficacy | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 9.51 |
| Age, Customized < 50 years | 4 Participants |
| Age, Customized ≥ 50 Years | 11 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 15 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 2 | 0 / 8 |
| other Total, other adverse events | 9 / 15 | 1 / 2 | 5 / 8 |
| serious Total, serious adverse events | 1 / 15 | 0 / 2 | 0 / 8 |
Outcome results
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.
Time frame: Week 16 to Week 28
Population: Assessed in participants in the randomized-withdrawal period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) | 2 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) | 7 Participants |
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.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at week 16 | -3.00 cells per hour | Standard Deviation 6.51 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline | 9.33 cells per hour | Standard Deviation 5.65 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at week 28 | -2.00 cells per hour | Standard Deviation 6.96 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at week 16 | -7.00 cells per hour | Standard Deviation 1.41 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline | 9.50 cells per hour | Standard Deviation 2.12 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at week 28 | -6.00 cells per hour | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Baseline | 10.9 cells per hour | Standard Deviation 7.38 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at week 28 | -1.20 cells per hour | Standard Deviation 7.46 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Change at week 16 | -3.43 cells per hour | Standard Deviation 6.68 |
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 1. Slight 2. Mild 3. Moderate 4. Moderate to severe 5. Severe 6. Very Severe 17 organ domains were rated and summed to create a total score (range 0-102, higher scores correspond with more severity).
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Change at week 16 | -0.57 score on a scale | Standard Deviation 0.85 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Baseline | 2.53 score on a scale | Standard Deviation 3 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Change at week 28 | -1.00 score on a scale | Standard Deviation 1.1 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Change at week 16 | -1.00 score on a scale | Standard Deviation 1.41 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Baseline | 7.50 score on a scale | Standard Deviation 4.95 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Change at week 28 | -2.00 score on a scale | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Baseline | 2.38 score on a scale | Standard Deviation 1.85 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Change at week 28 | -0.80 score on a scale | Standard Deviation 1.1 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score | Change at week 16 | -0.75 score on a scale | Standard Deviation 0.89 |
Secondary
Change From Baseline in FACIT-F Score (Fatigue Scale)
FACIT-F score Total score range: 0-52, lower scores correspond with more fatigue.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Change at Week 28 | 5.00 score on a scale | Standard Deviation 12.8 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Change at Week 16 | 1.86 score on a scale | Standard Deviation 9.58 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Baseline | 38.1 score on a scale | Standard Deviation 10.8 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Change at Week 16 | -1.50 score on a scale | Standard Deviation 2.12 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Baseline | 51.0 score on a scale | Standard Deviation 0 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Change at Week 28 | 0 score on a scale | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Baseline | 37.9 score on a scale | Standard Deviation 12.4 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Change at Week 28 | 6.25 score on a scale | Standard Deviation 14.5 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in FACIT-F Score (Fatigue Scale) | Change at Week 16 | 5.62 score on a scale | Standard Deviation 9.64 |
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.
Time frame: Baseline and week 16
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Baseline | 92.1 FVC % predicted | Standard Deviation 19.8 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Change at week 16 | -2.69 FVC % predicted | Standard Deviation 4.89 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Baseline | 113 FVC % predicted | Standard Deviation 14.9 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Change at week 16 | -11.0 FVC % predicted | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Baseline | 95.9 FVC % predicted | Standard Deviation 17.3 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted | Change at week 16 | -1.38 FVC % predicted | Standard Deviation 4.78 |
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.
Time frame: Baseline, and week 16
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | Baseline | 92.6 DLCO % predicted | Standard Deviation 21.4 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | Change at week 16 | -14.8 DLCO % predicted | Standard Deviation 23.5 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | Baseline | 90 DLCO % predicted | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | Baseline | 93.5 DLCO % predicted | Standard Deviation 22.8 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted | Change at week 16 | -18.4 DLCO % predicted | Standard Deviation 28.9 |
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.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Change at week 16 | -4.86 units on a scale (mm) | Standard Deviation 17.8 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Baseline | 33.1 units on a scale (mm) | Standard Deviation 22.7 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Change at week 28 | -3.00 units on a scale (mm) | Standard Deviation 34.4 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Change at week 16 | 0.50 units on a scale (mm) | Standard Deviation 7.78 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Baseline | 11.5 units on a scale (mm) | Standard Deviation 9.19 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Change at week 28 | -5.00 units on a scale (mm) | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Baseline | 27.4 units on a scale (mm) | Standard Deviation 23.6 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Change at week 28 | -2.50 units on a scale (mm) | Standard Deviation 39.8 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) | Change at week 16 | -11.1 units on a scale (mm) | Standard Deviation 19.9 |
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.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Change at week 16 | -22.8 units on a scale (mm) | Standard Deviation 22.2 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Baseline | 48.0 units on a scale (mm) | Standard Deviation 13.2 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Change at week 28 | -31.8 units on a scale (mm) | Standard Deviation 13.5 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Change at week 16 | -13.0 units on a scale (mm) | Standard Deviation 5.66 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Baseline | 38.5 units on a scale (mm) | Standard Deviation 20.5 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Change at week 28 | -21.0 units on a scale (mm) | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Baseline | 45.3 units on a scale (mm) | Standard Deviation 13.9 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Change at week 28 | -34.0 units on a scale (mm) | Standard Deviation 13.9 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) | Change at week 16 | -35.6 units on a scale (mm) | Standard Deviation 11.3 |
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.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Change at week 16 | 18.1 U/L | Standard Deviation 24.6 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Baseline | 35.4 U/L | Standard Deviation 23.5 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Change at week 28 | 7.17 U/L | Standard Deviation 20.4 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Change at week 16 | 55.5 U/L | Standard Deviation 51.6 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Baseline | 63.0 U/L | Standard Deviation 7.07 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Change at week 28 | 14.0 U/L | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Baseline | 32.6 U/L | Standard Deviation 26.6 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Change at week 28 | 5.80 U/L | Standard Deviation 22.5 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum Angiotensin Converting Enzyme | Change at week 16 | 8.12 U/L | Standard Deviation 11.9 |
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.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Change at week 16 | -0.20 mg/dL | Standard Deviation 0.76 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Baseline | 0.52 mg/dL | Standard Deviation 0.49 |
| Double-Blind Sarilumab (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Change at week 28 | -0.20 mg/dL | Standard Deviation 0.55 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Change at week 16 | -0.90 mg/dL | Standard Deviation 1.13 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Baseline | 0.90 mg/dL | Standard Deviation 1.13 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Change at week 28 | 0 mg/dL | — |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Baseline | 0.41 mg/dL | Standard Deviation 0.42 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Change at week 28 | -0.24 mg/dL | Standard Deviation 0.61 |
| Double-Blind Placebo (Post-randomization) | Change From Baseline in Serum C-Reactive Protein (CRP) | Change at week 16 | -0.22 mg/dL | Standard Deviation 0.53 |
Secondary
Change in Prednisone Dose
Time frame: Baseline, week 16, and week 28
Population: Data were not collected for this outcome
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.
Time frame: Baseline and week 16
Population: Data were collected during the open-label portion of the study only
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Change in Pulmonary Function (FEV1) Percent Predicted | Baseline | 89.0 FEV1 % predicted | Standard Deviation 19.86 |
| Double-Blind Sarilumab (Post-randomization) | Change in Pulmonary Function (FEV1) Percent Predicted | Week 16 | 86.0 FEV1 % predicted | Standard Deviation 18.25 |
Secondary
Change in Size of Sarcoidosis Lesions
Time frame: Baseline, week 16, and week 28
Population: Data were not collected for this outcome
Secondary
Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range
Normal range as calculated by the local laboratory.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range | Week 16 | 0 Participants |
Secondary
Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range
Normal range as calculated by the local laboratory.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range | Week 16 | 0 Participants |
Secondary
Number of Participants With Serum Creatinine Outside Normal Range
Normal range as calculated by the local laboratory.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Serum Creatinine Outside Normal Range | Week 16 | 0 Participants |
Secondary
Number of Participants With Urine Protein Outside Normal Range
Normal range as calculated by the local laboratory.
Time frame: Baseline, week 16, and week 28
Population: Participants with available data at each respective time point are included in the analysis
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Sarilumab (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Week 16 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Baseline | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Week 28 | 0 Participants |
| Double-Blind Placebo (Post-randomization) | Number of Participants With Urine Protein Outside Normal Range | Week 16 | 0 Participants |
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
Time frame: Baseline, week 16, and week 28
Population: Participants who presented with inflammatory arthritis and with available data at each respective time point are included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Baseline - swollen joints | 20 joints |
| Double-Blind Sarilumab (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Baseline - tender joints | 20 joints |
| Double-Blind Sarilumab (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 16 - tender joints | 4 joints |
| Double-Blind Sarilumab (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 16 - swollen joints | 18 joints |
| Double-Blind Sarilumab (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 28 - tender joints | 0 joints |
| Double-Blind Sarilumab (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 28 - swollen joints | 8 joints |
| Double-Blind Placebo (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 28 - tender joints | 0 joints |
| Double-Blind Placebo (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 16 - swollen joints | 16 joints |
| Double-Blind Placebo (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Baseline - tender joints | 18 joints |
| Double-Blind Placebo (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Baseline - swollen joints | 18 joints |
| Double-Blind Placebo (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 28 - swollen joints | 8 joints |
| Double-Blind Placebo (Post-randomization) | Number of Tender and Swollen Joints Per 68/66 Joint Evaluation | Week 16 - tender joints | 0 joints |
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).
Time frame: Baseline, week 16, and week 28
Population: Participants who presented with cutaneous sarcoidosis and with available data at each respective time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Sarilumab (Post-randomization) | Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Week 16 | 16.7 score on a scale | Standard Deviation 15.5 |
| Double-Blind Sarilumab (Post-randomization) | Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Baseline | 12.7 score on a scale | Standard Deviation 9.29 |
| Double-Blind Placebo (Post-randomization) | Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Baseline | 9.5 score on a scale | Standard Deviation 10.61 |
| Double-Blind Placebo (Post-randomization) | Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Week 16 | 9.0 score on a scale | Standard Deviation 11.31 |
| Double-Blind Placebo (Post-randomization) | Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis | Week 28 | 9.0 score on a scale | Standard Deviation 11.31 |