Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis

• Register: ClinicalTrials.gov
• Last refreshed on: 16 October 2023
• Main ID: NCT04008069
• Date of registration: 25/06/2019
• Prospective Registration: Yes
• Primary sponsor: Stanford University
• Public title: Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
• Scientific title: A Phase II, Single-Site, Double-Blind, Placebo-Controlled Randomized Withdrawal Study Assessing the Efficacy and Safety of Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
• Date of first enrolment: September 3, 2019
• Target sample size: 16
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT04008069
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Matthew Baker, MD
• Affiliation: Stanford University

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Sarcoidosis

Intervention(s)

Drug: Placebo

Drug: Sarilumab

Primary Outcome(s)

Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) [Time Frame: Week 16 to Week 28]

Secondary Outcome(s)

Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS) [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in Serum Angiotensin Converting Enzyme [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in Erythrocyte Sedimentation Rate (ESR) [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted [Time Frame: Baseline, and week 16]

Change in Prednisone Dose [Time Frame: Baseline, week 16, and week 28]

Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range [Time Frame: Baseline, week 16, and week 28]

Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in FACIT-F Score (Fatigue Scale) [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS) [Time Frame: Baseline, week 16, and week 28]

Change in Size of Sarcoidosis Lesions [Time Frame: Baseline, week 16, and week 28]

Number of Participants With Serum Creatinine Outside Normal Range [Time Frame: Baseline, week 16, and week 28]

Number of Tender and Swollen Joints Per 68/66 Joint Evaluation [Time Frame: Baseline, week 16, and week 28]

Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis [Time Frame: Baseline, week 16, and week 28]

Change in Pulmonary Function (FEV1) Percent Predicted [Time Frame: Baseline and week 16]

Number of Participants With Urine Protein Outside Normal Range [Time Frame: Baseline, week 16, and week 28]

Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted [Time Frame: Baseline and week 16]

Change From Baseline in Serum C-Reactive Protein (CRP) [Time Frame: Baseline, week 16, and week 28]

Secondary ID(s)

48375

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 05/10/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT04008069