SarcoidosisPhase 2NCT04008069
Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
A Phase 2 study testing Sarilumab in people with Sarcoidosis, run by Stanford University at 1 site in United States.
Trial summary
The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Sarcoidosis
- What is being tested?
- Sarilumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Sep 2019to 9 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.
Read the 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.
- Conditions
- Sarcoidosis
- Being tested
- Sarilumab, Placebo
- Keywords
- glucocorticoid-dependent
- Medical subject headings
- Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SarilumabDrug
Also called Kevzara
Sarilumab 200 mg administered subcutaneously
PlaceboDrug
Placebo administered subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Open-Label Sarilumab (pre-randomization) | Experimental | On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 16 to Week 28
Secondary outcomes (18)
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.
Measured: Baseline and week 16
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.
Measured: Baseline, and week 16
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.
Measured: Baseline and week 16
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
- Slight
- Mild
- Moderate
- Moderate to severe
- Severe
- Very Severe 17 organ domains were rated and summed to create a total score (range 0-102, higher scores correspond with more severity).
Measured: Baseline, week 16, and week 28
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.
Measured: Baseline, week 16, and week 28
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.
Measured: Baseline, week 16, and week 28
Change From Baseline in FACIT-F Score (Fatigue Scale)
FACIT-F score
Total score range: 0-52, lower scores correspond with more fatigue.
Measured: Baseline, week 16, and week 28
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
Measured: Baseline, week 16, and week 28
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).
Measured: Baseline, week 16, and week 28
Change in Size of Sarcoidosis Lesions
Measured: Baseline, week 16, and week 28
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.
Measured: Baseline, week 16, and week 28
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.
Measured: Baseline, week 16, and week 28
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.
Measured: Baseline, week 16, and week 28
Change in Prednisone Dose
Measured: Baseline, week 16, and week 28
Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range
Normal range as calculated by the local laboratory.
Measured: Baseline, week 16, and week 28
Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range
Normal range as calculated by the local laboratory.
Measured: Baseline, week 16, and week 28
Number of Participants With Serum Creatinine Outside Normal Range
Normal range as calculated by the local laboratory.
Measured: Baseline, week 16, and week 28
Number of Participants With Urine Protein Outside Normal Range
Normal range as calculated by the local laboratory.
Measured: Baseline, week 16, and week 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jul 2019
- Study start3 Sep 2019
- Primary completion26 Jul 2022
- Study completion9 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SarcoidosisStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew C. Baker, Stanford University
- Investigators
- Matthew Baker, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04008069
- Sponsor's protocol ID
- 48375
- Status last verified
- Oct 2023
- First submitted
- 25 Jun 2019
- Last updated
- 5 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 37471590
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04008069
- Acronym / sponsor ID
- 48375
- Conditions
- Sarcoidosis
- Keywords
- glucocorticoid-dependent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 3 Sep 2019 (actual)
- Primary completion
- 26 Jul 2022 (actual)
- Study completion
- 9 Sep 2022 (actual)
- First posted
- 5 Jul 2019 (actual)
- Results
- Posted 5 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Open-Label Sarilumab (pre-randomization) | Experimental | Drug: SarilumabOn entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks. |
| Double-Blind Sarilumab (post-randomization) | Experimental | Drug: SarilumabAfter completing the open-label period, participants are randomized in blinded fashion to receive sarilumab every two weeks for 12 weeks. |
| Double-Blind Placebo (post-randomization) | Placebo comparator | Drug: PlaceboAfter completing the open-label period, participants are randomized in blinded fashion to receive placebo every two weeks for 12 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (21 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SarilumabAlso: KevzaraSarilumab 200 mg administered subcutaneously | Drug | Double-Blind Sarilumab (post-randomization), Open-Label Sarilumab (pre-randomization) |
| PlaceboPlacebo administered subcutaneously | Drug | Double-Blind Placebo (post-randomization) |
Primary outcome
Number of Participants Without Sarcoidosis Flare (Flare-Free Survival)
Time frame: 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.
18 secondary outcomes
Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted
Time frame: Baseline and week 16
Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted
Time frame: Baseline, and week 16
Change in Pulmonary Function (FEV1) Percent Predicted
Time frame: Baseline and week 16
Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score
Time frame: Baseline, week 16, and week 28
Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS)
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 From Baseline in FACIT-F Score (Fatigue Scale)
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 Size of Sarcoidosis Lesions
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 Serum C-Reactive Protein (CRP)
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 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
Number of Participants With Serum Creatinine Outside Normal Range
Time frame: Baseline, week 16, and week 28
Number of Participants With Urine Protein Outside Normal Range
Time frame: Baseline, week 16, and week 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37471590Baker 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Baker, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sarilumab in people with Sarcoidosis, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Without Sarcoidosis Flare (Flare-Free Survival) (time frame: Week 16 to Week 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04008069, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.