Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis

• ClinicalTrials.gov Identifier: NCT04008069
• Recruitment Status: Active, not recruiting
• First Posted: July 5, 2019
• Last Update Posted: January 27, 2022
• Sponsor: Stanford University
• Information provided by (Responsible Party): Matthew C. Baker, Stanford University

Tracking Information

• First Submitted Date: June 25, 2019
• First Posted Date: July 5, 2019
• Last Update Posted Date: January 27, 2022
• Actual Study Start Date: September 3, 2019
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 2, 2019)

flare-free survival of sarilumab-treated patients compared to placebo-treated controls [ Time Frame: 2 weeks ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 2, 2019)

• Change in physician and patient assessments [ Time Frame: 2 weeks ]
  extrapulmonary physician organ severity tool (ePOST) Score Description:

  1. Slight
  2. Mild
  3. Moderate
  4. Moderate to severe
  5. Severe
  6. Very Severe
• change in FACIT-F score (fatigue scale [ Time Frame: 2 weeks ]
  FACIT-F score Scale: 0: Not at all

  1. A little
  2. Somewhat
  3. Ouite a bit
  4. Very much
• change in prednisone dose [ Time Frame: 2 weeks ]
  prednisone dose
• change in pulmonary function tests (FVC) [ Time Frame: 2 weeks ]
  pulmonary function test (FVC)
• change in ALT [ Time Frame: 2 weeks ]
  ALT
• change in serum creatinine [ Time Frame: 2 weeks ]
  Serum creatinine
• change in the Sarcoidosis Activity and Severity Index for cutaneous sarcoidosis [ Time Frame: 2 weeks ]
  Sarcoidosis Activity and Severity Index
• change in size of sarcoidosis lesions [ Time Frame: 2 weeks ]
  size of sarcoidosis lesions
• Change in Pulmonary Function (FEV1) [ Time Frame: 2 weeks ]
  FEV1
• change in AST [ Time Frame: 2 weeks ]
  AST
• Change in Urine Protein level [ Time Frame: 2 weeks ]
  Urine protein
• 68/66 Joint evaluation [ Time Frame: 2 weeks ]
  Joint evaluation Score: 0: Absent 1: Present 9: Not applicable

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
• Official 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
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.

Masking: Triple (Participant, Care Provider, 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.

Primary Purpose: Treatment

• Condition: Sarcoidosis

Intervention

• Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]_#1
  Sarilumab vs Placebo
• Drug: Placebos
  Placebo

Study Arms

• Experimental: Study drug
  sarilumab 200 mg subcutaneously every two weeks
  Intervention: Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]_#1
• Placebo Comparator: placebo
  placebo subcutaneously every two weeks
  Intervention: Drug: Placebos

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 2, 2019): 15
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04008069
• Other Study ID Numbers: 48375
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Matthew C. Baker, Stanford University
• Study Sponsor: Stanford University
• Collaborators: Not Provided

Investigators

• Principal Investigator: Mark Genovese, MD; Stanford University

• PRS Account: Stanford University
• Verification Date: January 2022