Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis

NCT04008069 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 48375
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.

Conditions

Sarcoidosis

Keywords

glucocorticoid-dependent

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (18)

• Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted

  Baseline and week 16

• Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted

  Baseline, and week 16

• Change in Pulmonary Function (FEV1) Percent Predicted

  Baseline and week 16

• Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score

  Baseline, week 16, and week 28

• Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS)

  Baseline, week 16, and week 28

Study Arms (3)

Open-Label Sarilumab (pre-randomization)

EXPERIMENTAL

On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks.

Drug: Sarilumab

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.

Drug: Sarilumab

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.

Drug: Placebo

Interventions

Sarilumab DRUG

Sarilumab 200 mg administered subcutaneously

Also known as: Kevzara

Double-Blind Sarilumab (post-randomization); Open-Label Sarilumab (pre-randomization)

Placebo DRUG

Placebo administered subcutaneously

Double-Blind Placebo (post-randomization)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University

Palo Alto, California, 94304, United States

Location

Related Publications (1)

• 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.

  PMID: 37471590 DERIVED

MeSH Terms

Conditions

Sarcoidosis

Interventions

sarilumab

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Dr. Matthew C. Baker, Principal Investigator
• Organization: Stanford University, School of Medicine, Immunology & Rheumatology

mbake13@stanford.edu

650- 498-4528

Study Officials

• Matthew Baker, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study doctor and personnel will not know whether you are assigned to the sarilumab group or the placebo group after Week 16.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 25, 2019
• First Posted: July 5, 2019
• Study Start: September 3, 2019
• Primary Completion: July 26, 2022
• Study Completion: September 9, 2022
• Last Updated: October 5, 2023
• Results First Posted: October 5, 2023

Record last verified: 2023-10

Locations

US (1)