Trial Outcomes & Findings for Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis (NCT NCT04008069)

NCT ID: NCT04008069

Last Updated: 2023-10-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: Week 16 to Week 28
• Results posted on: 2023-10-05

Participant Flow

Sixteen participants were screened, fifteen met eligibility criteria and were allocated to treatment.

Participant milestones

Measure	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.	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.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Open-Label Period STARTED	15	0	0
Open-Label Period Completed Treatment up to Week 16	10	0	0
Open-Label Period COMPLETED	10	0	0
Open-Label Period NOT COMPLETED	5	0	0
Randomized-Withdrawal Period STARTED	0	2	8
Randomized-Withdrawal Period Completed Treatment With Study Drug	0	1	5
Randomized-Withdrawal Period COMPLETED	0	1	5
Randomized-Withdrawal Period NOT COMPLETED	0	1	3

Reasons for withdrawal

Measure	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.	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.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
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

Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis

Baseline characteristics by cohort

Measure	All Participants n=15 Participants Participants who enter the study, to receive open-label sarilumab every two weeks for 16 weeks.
Age, Continuous	56.1 years STANDARD_DEVIATION 9.51 • n=5 Participants
Age, Customized < 50 years	4 Participants n=5 Participants
Age, Customized ≥ 50 Years	11 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 16 to Week 28

Population: Assessed in participants in the randomized-withdrawal period

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.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Number of Participants Without Sarcoidosis Flare (Flare-Free Survival)	2 Participants	7 Participants	—

SECONDARY outcome

Timeframe: Baseline and week 16

Population: Participants with available data at each respective time point are included in the analysis

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.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted Baseline	92.1 FVC % predicted Standard Deviation 19.8	113 FVC % predicted Standard Deviation 14.9	95.9 FVC % predicted Standard Deviation 17.3
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted Change at week 16	-2.69 FVC % predicted Standard Deviation 4.89	-11.0 FVC % predicted Standard Deviation NA Not calculable for n of 1	-1.38 FVC % predicted Standard Deviation 4.78

SECONDARY outcome

Timeframe: Baseline, and week 16

Population: Participants with available data at each respective time point are included in the analysis

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.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=1 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted Baseline	92.6 DLCO % predicted Standard Deviation 21.4	90 DLCO % predicted Standard Deviation NA Not calculable for n of 1	93.5 DLCO % predicted Standard Deviation 22.8
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	—	-18.4 DLCO % predicted Standard Deviation 28.9

SECONDARY outcome

Timeframe: Baseline and week 16

Population: Data were collected during the open-label portion of the study only

FEV1 percent predicted is a normalized value of FEV1 calculated using the Knudson equation and based upon participant age, gender, and height.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change in Pulmonary Function (FEV1) Percent Predicted Baseline	89.0 FEV1 % predicted Standard Deviation 19.86	—	—
Change in Pulmonary Function (FEV1) Percent Predicted Week 16	86.0 FEV1 % predicted Standard Deviation 18.25	—	—

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

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).

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score Baseline	2.53 score on a scale Standard Deviation 3.00	7.50 score on a scale Standard Deviation 4.95	2.38 score on a scale Standard Deviation 1.85
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	-1.00 score on a scale Standard Deviation 1.41	-0.75 score on a scale Standard Deviation 0.89
Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score Change at week 28	-1.00 score on a scale Standard Deviation 1.10	-2.00 score on a scale Standard Deviation NA Not calculable for n of 1	-0.80 score on a scale Standard Deviation 1.10

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

Physician rates patient's disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) Baseline	48.0 units on a scale (mm) Standard Deviation 13.2	38.5 units on a scale (mm) Standard Deviation 20.5	45.3 units on a scale (mm) Standard Deviation 13.9
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	-13.0 units on a scale (mm) Standard Deviation 5.66	-35.6 units on a scale (mm) Standard Deviation 11.3
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	-21.0 units on a scale (mm) Standard Deviation NA Not calculable for n of 1	-34.0 units on a scale (mm) Standard Deviation 13.9

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

Patient rates their disease on a 100 mm VAS. Score range: 0 to 100, higher scores correspond to worse disease state.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) Baseline	33.1 units on a scale (mm) Standard Deviation 22.7	11.5 units on a scale (mm) Standard Deviation 9.19	27.4 units on a scale (mm) Standard Deviation 23.6
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	0.50 units on a scale (mm) Standard Deviation 7.78	-11.1 units on a scale (mm) Standard Deviation 19.9
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	-5.00 units on a scale (mm) Standard Deviation NA Not calculable for n of 1	-2.50 units on a scale (mm) Standard Deviation 39.8

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis.

FACIT-F score

Total score range: 0-52, lower scores correspond with more fatigue.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in FACIT-F Score (Fatigue Scale) Baseline	38.1 score on a scale Standard Deviation 10.8	51.0 score on a scale Standard Deviation 0	37.9 score on a scale Standard Deviation 12.4
Change From Baseline in FACIT-F Score (Fatigue Scale) Change at Week 16	1.86 score on a scale Standard Deviation 9.58	-1.50 score on a scale Standard Deviation 2.12	5.62 score on a scale Standard Deviation 9.64
Change From Baseline in FACIT-F Score (Fatigue Scale) Change at Week 28	5.00 score on a scale Standard Deviation 12.8	0 score on a scale Standard Deviation NA Not calculable for n of 1	6.25 score on a scale Standard Deviation 14.5

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=1 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Number of Tender and Swollen Joints Per 68/66 Joint Evaluation Baseline - tender joints	20 joints	—	18 joints
Number of Tender and Swollen Joints Per 68/66 Joint Evaluation Baseline - swollen joints	20 joints	—	18 joints
Number of Tender and Swollen Joints Per 68/66 Joint Evaluation Week 16 - tender joints	4 joints	—	0 joints
Number of Tender and Swollen Joints Per 68/66 Joint Evaluation Week 16 - swollen joints	18 joints	—	16 joints
Number of Tender and Swollen Joints Per 68/66 Joint Evaluation Week 28 - tender joints	0 joints	—	0 joints
Number of Tender and Swollen Joints Per 68/66 Joint Evaluation Week 28 - swollen joints	8 joints	—	8 joints

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants who presented with cutaneous sarcoidosis and with available data at each respective time point.

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).

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=3 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis Baseline	12.7 score on a scale Standard Deviation 9.29	—	9.5 score on a scale Standard Deviation 10.61
Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis Week 16	16.7 score on a scale Standard Deviation 15.50	—	9.0 score on a scale Standard Deviation 11.31
Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis Week 28	—	—	9.0 score on a scale Standard Deviation 11.31

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Data were not collected for this outcome

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

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.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Serum Angiotensin Converting Enzyme Baseline	35.4 U/L Standard Deviation 23.5	63.0 U/L Standard Deviation 7.07	32.6 U/L Standard Deviation 26.6
Change From Baseline in Serum Angiotensin Converting Enzyme Change at week 16	18.1 U/L Standard Deviation 24.6	55.5 U/L Standard Deviation 51.6	8.12 U/L Standard Deviation 11.9
Change From Baseline in Serum Angiotensin Converting Enzyme Change at week 28	7.17 U/L Standard Deviation 20.4	14.0 U/L Standard Deviation NA Not calculable for n of 1	5.80 U/L Standard Deviation 22.5

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

CRP is a protein made by the liver. The level of CRP increases when there's inflammation in the body.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Serum C-Reactive Protein (CRP) Baseline	0.52 mg/dL Standard Deviation 0.49	0.90 mg/dL Standard Deviation 1.13	0.41 mg/dL Standard Deviation 0.42
Change From Baseline in Serum C-Reactive Protein (CRP) Change at week 16	-0.20 mg/dL Standard Deviation 0.76	-0.90 mg/dL Standard Deviation 1.13	-0.22 mg/dL Standard Deviation 0.53
Change From Baseline in Serum C-Reactive Protein (CRP) Change at week 28	-0.20 mg/dL Standard Deviation 0.55	0 mg/dL Standard Deviation NA Not calculable for n of 1	-0.24 mg/dL Standard Deviation 0.61

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

ESR is the rate at which red blood cells in anticoagulated whole blood descend in a standardized tube over a period of one hour.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Baseline	9.33 cells per hour Standard Deviation 5.65	9.50 cells per hour Standard Deviation 2.12	10.9 cells per hour Standard Deviation 7.38
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Change at week 16	-3.00 cells per hour Standard Deviation 6.51	-7.00 cells per hour Standard Deviation 1.41	-3.43 cells per hour Standard Deviation 6.68
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Change at week 28	-2.00 cells per hour Standard Deviation 6.96	-6.00 cells per hour Standard Deviation NA Not calculable for n of 1	-1.20 cells per hour Standard Deviation 7.46

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Data were not collected for this outcome

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

Normal range as calculated by the local laboratory.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range Week 28	0 Participants	0 Participants	0 Participants
Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range Baseline	0 Participants	0 Participants	0 Participants
Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range Week 16	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

Normal range as calculated by the local laboratory.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range Baseline	0 Participants	0 Participants	0 Participants
Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range Week 16	0 Participants	0 Participants	0 Participants
Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range Week 28	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

Normal range as calculated by the local laboratory.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Number of Participants With Serum Creatinine Outside Normal Range Baseline	0 Participants	0 Participants	0 Participants
Number of Participants With Serum Creatinine Outside Normal Range Week 16	0 Participants	0 Participants	0 Participants
Number of Participants With Serum Creatinine Outside Normal Range Week 28	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, week 16, and week 28

Population: Participants with available data at each respective time point are included in the analysis

Normal range as calculated by the local laboratory.

Outcome measures

Measure	Double-Blind Sarilumab (Post-randomization) n=15 Participants After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=2 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 Participants After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Number of Participants With Urine Protein Outside Normal Range Baseline	0 Participants	0 Participants	0 Participants
Number of Participants With Urine Protein Outside Normal Range Week 16	0 Participants	0 Participants	0 Participants
Number of Participants With Urine Protein Outside Normal Range Week 28	0 Participants	0 Participants	0 Participants

Adverse Events

Open-Label Sarilumab (Pre-randomization)

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Double-Blind Sarilumab (Post-randomization)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Double-Blind Placebo (Post-randomization)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Measure	Open-Label Sarilumab (Pre-randomization) n=15 participants at risk On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks.	Double-Blind Sarilumab (Post-randomization) n=2 participants at risk After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 participants at risk After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Infections and infestations COVID-19	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks

Other adverse events

Measure	Open-Label Sarilumab (Pre-randomization) n=15 participants at risk On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks.	Double-Blind Sarilumab (Post-randomization) n=2 participants at risk After completing the open-label period, participants are randomized to receive sarilumab every two weeks for 12 weeks.	Double-Blind Placebo (Post-randomization) n=8 participants at risk After completing the open-label period, participants are randomized receive placebo every two weeks for 12 weeks.
Investigations Transaminitis	13.3% 2/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	25.0% 2/8 • Up to 28 weeks
Blood and lymphatic system disorders Neutropenia	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Blood and lymphatic system disorders Prolonged neutropenia	0.00% 0/15 • Up to 28 weeks	50.0% 1/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Blood and lymphatic system disorders Thrombocytopenia	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	12.5% 1/8 • Up to 28 weeks
Blood and lymphatic system disorders Anemia	13.3% 2/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Skin and subcutaneous tissue disorders Rash	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Infections and infestations Herpes zoster	0.00% 0/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	12.5% 1/8 • Up to 28 weeks
Gastrointestinal disorders Ulcers aphthous oral	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Musculoskeletal and connective tissue disorders Myalgia	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Gastrointestinal disorders Diarrhea	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Eye disorders Peripheral vision defective	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/15 • Up to 28 weeks	50.0% 1/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Reproductive system and breast disorders Cervical radiculopathy	0.00% 0/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	12.5% 1/8 • Up to 28 weeks
Investigations Kappa light chain analysis increased	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Musculoskeletal and connective tissue disorders Herniated disc	0.00% 0/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	12.5% 1/8 • Up to 28 weeks
Investigations Creatinine kinase increased	0.00% 0/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	12.5% 1/8 • Up to 28 weeks
Blood and lymphatic system disorders Hyperbilirubinemia	0.00% 0/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	12.5% 1/8 • Up to 28 weeks
Musculoskeletal and connective tissue disorders Pain in (r) hip	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks
Psychiatric disorders Alcohol rehabilitation	6.7% 1/15 • Up to 28 weeks	0.00% 0/2 • Up to 28 weeks	0.00% 0/8 • Up to 28 weeks

Additional Information

Dr. Matthew C. Baker, Principal Investigator

Stanford University, School of Medicine, Immunology & Rheumatology

Phone: 650- 498-4528

Email: mbake13@stanford.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place