NCT03793439

Tofacitinib Hypothesis-generating, Pilot Study for Corticosteroid-Dependent Sarcoidosis

Completed Phase 1 Results posted Last updated 18 February 2022

What this trial tests

Phase 1 trial testing Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial in Sarcoidosis, Pulmonary in 5 participants. Completed in 24 June 2021.

Timeline

15 May 2019

Primary endpoint
24 June 2020

24 June 2021

Quick facts

Lead sponsor	Oregon Health and Science University
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	5
Start date	15 May 2019
Primary completion	24 June 2020
Estimated completion	24 June 2021
Sites	1 location across United States

Drugs / interventions tested

• Tofacitinib 5mg Oral Tablet [Xeljanz] 16 week trial — full drug profile →
• Spirometry
• RNA Sequencing
• Laboratory testing
• Corticosteroid — full drug profile →
• Tofacitinib 5mg [Xeljanz] 1 year open-label extension — full drug profile →

Conditions studied

• Sarcoidosis, Pulmonary — all drugs for Sarcoidosis, Pulmonary →
• Sarcoidosis Lung — all drugs for Sarcoidosis Lung →
• Sarcoidosis — all drugs for Sarcoidosis →

Sponsor

Oregon Health and Science University

Who can join

Adults 18 to 89, any sex, with Sarcoidosis, Pulmonary or Sarcoidosis Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With 50% Reduction in Corticosteroid Requirement Primary · 16 weeks

50% reduction in corticosteroid requirement by week 16, without significant decline in their pulmonary function-defined as a \>15% decline in forced vital capacity (FVC), forced expiratory volume at 1 second (FEV1), or diffusing capacity of lung for carbon monoxide (DLCO) relative to the baseline value

Group	Value	95% CI
Open Label	3

Number of Participants With Significantly Decreased Expression of STAT1 Mediated Genes as Determined by RNA Sequencing Secondary · 16 weeks

Peripheral blood RNA sequencing performed before and after 16 weeks of tofacitinib treatment. Significant changes are defined as at least 1.5 fold change in the expression of STAT1-mediated genes, with a false discover rate p value of \< 0.05.

Group	Value	95% CI
Open Label	0

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected from week 0 (start of study drug) until study drug was stopped, plus 4 weeks of post-treatment follow up. This corresponded to 72 weeks for subjects who completed the study and open-label extension: study (16 weeks), open-label extension (52 weeks), and post-treatment follow up (4 weeks). Adverse event data from subjects who terminated the study early were collected until study drug was stopped + 4 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Open Label

Serious: 2/5 (40%)

Deaths: 0/5

Serious adverse events (2 terms)

Reaction	System	Open Label
Peripheral motor neuropathy	Nervous system disorders	—
Skin infection	Skin and subcutaneous tissue disorders	—

Other adverse events (8 terms — click to expand)

Reaction	System	Open Label
Arthralgia	Musculoskeletal and connective tissue disorders	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—
Vomiting	Gastrointestinal disorders	—
Diarrhea	Gastrointestinal disorders	—
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Renal colic	Renal and urinary disorders	—
Bronchial infection	Respiratory, thoracic and mediastinal disorders	—

Most-reported serious reactions: Peripheral motor neuropathy, Skin infection.

Data from ClinicalTrials.gov NCT03793439 adverse events section.

Sponsor's own description

This is a pilot study to determine whether further research is warranted to assess whether tofacitinib is an effective steroid sparing treatment for pulmonary sarcoidosis. The primary endpoint for this study is a 50% or greater reduction in corticosteroid requirement.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens.
   Hu Q, Bian Q, Rong D, Wang L, et al · · 2023 · cited 190× · PMID 36911202 · DOI 10.3389/fbioe.2023.1110765
2. Janus kinase inhibition induces disease remission in cutaneous sarcoidosis and granuloma annulare.
   Damsky W, Thakral D, McGeary MK, Leventhal J, et al · · 2020 · cited 95× · PMID 31185230 · DOI 10.1016/j.jaad.2019.05.098
3. JAK-STAT signaling in human disease: From genetic syndromes to clinical inhibition.
   Luo Y, Alexander M, Gadina M, O'Shea JJ, et al · · 2021 · cited 92× · PMID 34625141 · DOI 10.1016/j.jaci.2021.08.004
4. The Promise of JAK Inhibitors for Treatment of Sarcoidosis and Other Inflammatory Disorders with Macrophage Activation: A Review of the Literature.
   Wang A, Singh K, Ibrahim W, King B, et al · · 2020 · cited 64× · PMID 32226347
5. Treatment of Multiorgan Sarcoidosis With Tofacitinib.
   Damsky W, Young BD, Sloan B, Miller EJ, et al · · 2020 · cited 54× · PMID 31916703 · DOI 10.1002/acr2.11112
6. Refractory Sarcoidosis: A Review.
   El Jammal T, Jamilloux Y, Gerfaud-Valentin M, Valeyre D, et al · · 2020 · cited 45× · PMID 32368072 · DOI 10.2147/tcrm.s192922
7. Tofacitinib as a Steroid-Sparing Therapy in Pulmonary Sarcoidosis, an Open-Label Prospective Proof-of-Concept Study.
   Friedman MA, Le B, Stevens J, Desmarais J, et al · · 2021 · cited 36× · PMID 33825964 · DOI 10.1007/s00408-021-00436-8
8. Comprehensive Care for Patients with Sarcoidosis.
   Moor CC, Kahlmann V, Culver DA, Wijsenbeek MS. · · 2020 · cited 32× · PMID 32024123 · DOI 10.3390/jcm9020390