Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus
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|ClinicalTrials.gov Identifier: NCT02535689|
Recruitment Status : Completed
First Posted : August 31, 2015
Last Update Posted : August 9, 2018
Systemic lupus erythematosus (lupus) is an autoimmune disease that often involves many systems and organs of the body. Symptoms can include fever, joint pains, and rashes. Serious lupus can also damage organs like the kidneys, lungs, or brain. Drugs used for lupus can have serious side effects. Also, the drugs don t help some people. Researchers want to find new, more effective and safe treatments.
To evaluate the safety and tolerability of the drug tofacitinib (study drug) in people with lupus.
People ages 18 and older who have mild to moderate lupus and are not currently or haven t recently had certain lupus treatments.
Participants will be screened in another protocol.
Participants will have 7 five-hour visits over about 3 months. They will fill out multiple questionnaires. They will have tests, including:
- Physical exam
- Blood and urine tests
- ECG/EKG: Soft electrodes are stuck to the skin to monitor the heart.
- Optional SphygmoCor: Cuffs are attached to the arm and thigh to measure blood pressure and flow speed.
- Optional Endopat: A thimble-shaped cup is placed on the finger to measure blood flow. A cuff is put on the arm to measure blood pressure and flow.
- Optional CAVI: ECG electrodes are placed on both wrists, a microphone placed on the chest, and a blood pressure cuff placed on each arm and leg to measure blood pressure and velocity.
Participants will receive either the study drug or a placebo. They will take this twice a day by mouth for 56 days.
Participants will be contacted by phone 4 times....
|Condition or disease||Intervention/treatment||Phase|
|Systemic Lupus Erythematosus||Drug: Tofacitinib Drug: Placebo||Phase 1|
Systemic Lupus Erythematosus (SLE) is an autoimmune disease with variegated clinical presentation resulting from involvement of multiple biologic pathways. The pathways that lead to loss of tolerance in SLE include: multiple autoreactive cell types (B, T, dendritic, Th17 and regulatory T cells) and abnormal cytokine milieus, genetic factors, environmental and hormonal influences, all of which can influence cell differentiation patterns and reset tolerance checkpoints. In addition, recent studies indicate a putative role for neutrophils in lupus pathogenesis and associated end-organ damage. Currently available therapeutics are frequently inadequate to treat disease flares and simultaneously expose patients to potentially serious toxicities. Further, premature cardiovascular disease not explained by the Framingham risk equation has become one of the most important causes of morbidity and mortality in this patient population. To date, no treatment used in lupus appears to significantly decrease cardiovascular risk. Identifying a drug that has immunomodulatory effects and is also vasculoprotective is an unmet need in this disease.
Tofacitinib is an orally administered Janus kinase (JAK) inhibitor that has recently been approved by the Food and Drug Administration for the treatment of moderate to severe rheumatoid arthritis (RA).
The JAKs are a family of intracellular enzymes (JAK1, 2 and 3 and TYK2) that mediate signaling via a broad range of cytokine receptors. Targeting JAKs is an attractive therapeutic possibility for SLE for many reasons. Many of the inflammatory cytokines implicated in the pathogenesis of SLE signal via the JAK-STAT pathways. JAK inhibitors have been found to have efficacy in various murine models of lupus. Mice treated with a JAK2 inhibitor exhibited reduced serum levels of IL-6, and IL-17 along with reduced numbers of long-lived autoantibody producing plasma cells in the spleen and bone marrow. Furthermore, we have found that administration of tofacitinib reduced serum levels of ANA, IL-6, and IFN-gamma; and ameliorated glomerulonephritis (unpublished data).
This study therefore represents an innovative investigative measure of the safety and efficacy of JAK inhibition in SLE that is predicted by genetic predisposition. We will also investigate effects of tofacitinib on vascular function in SLE subjects and identify biomarkers that may be useful as endpoints in future studies.
To determine the safety and tolerability of tofacitinib in patients with SLE and mild to moderate disease activity.
This is a Phase Ib, randomized, double blind, placebo controlled clinical trial of orally administered tofacitinib, 5 mg twice daily, for the treatment of SLE subjects with mild to moderate disease activity stratified by the presence or absence of STAT4 risk alleles.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Safety of Tofacitinib, an Oral Janus Kinase Inhibitor, in Systemic Lupus Erythematosus; a Phase Ib Clinical Trial and Associated Mechanistic Studies|
|Study Start Date :||August 28, 2015|
|Actual Primary Completion Date :||April 26, 2018|
|Actual Study Completion Date :||April 26, 2018|
Active Comparator: 1
ARM 1: 10 of SLE patients will be heterozygous or homozygous for the STAT 4 risk alleles, receive treatment with tofacitinib 5 mg twice daily.
Oral administration of tofacitinib, 5 mg
Active Comparator: 2
ARM 2: 10 of SLE patients will NOT be heterozygous or homozygous for the STAT 4 risk alleles, receive treatment with tofacitinib 5 mg twice daily.
Oral administration of tofacitinib, 5 mg
Placebo Comparator: 3
ARM 3: 10 of SLE patients will be with variable genotypes will receive placebo twice daily.
- The primary endpoint is safety of tofacitinib in SLE subjects. [ Time Frame: 5 years ]
- Assessments of clinical response. [ Time Frame: 5 years ]Assessment of biologic effects.
- Assessment of biologic effects. [ Time Frame: 5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02535689
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Sarfaraz A Hasni, M.D.||National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)|