Autoimmune diseases occur when the immune system mistakenly flags certain cells in the body as foreign invaders. The resulting attack can cause irreparable damage to critical organs and tissues. For example, in multiple sclerosis, it’s the myelin coating that insulates nerve cells; in lupus, it can be any number of organs or systems that are damaged. Currently, many of the primary methods to treat patients with autoimmune disease utilize immune suppressors, which help reduce the inflammatory attack on tissues but can put patients at higher risk for developing infections.
Immune tolerance therapies are designed to stop, or even prevent, the autoimmune disease while leaving the body's disease-fighting abilities intact. These tolerance therapies essentially reprogram the immune system, so that a short course of treatment will have long-lasting, perhaps lifelong effects. While immune tolerance therapies are mainly experimental, the Immune Tolerance Network (ITN) believes that targeted reprogramming of the immune system holds a great deal of promise to effectively treat autoimmune diseases with fewer side effects than current drugs.
The clinical heterogeneity of the more than 80 autoimmune diseases presents a significant challenge with respect to the development of therapies designed to re-establish self-tolerance. The ITN’s approach to tolerance in autoimmune diseases attempts to address these challenges through a coordinated program of clinical studies aimed at establishing proof-of-principle either in diseases where a self-antigen has been identified, the target organ is accessible for further study or the disease pathogenesis has been relatively well established.
Given the complex nature of these diseases, and following the approaches being developed in the transplant and allergy portfolios, the ITN builds on results from ongoing trials by developing combination approaches affecting humoral and cellular, as well as adaptive and innate, immune responses. This includes combinations that ablate or anergize effector responses, deviate induced responses and boost regulatory responses. Because combination therapy trials can be logistically and scientifically challenging, the ITN has adopted the use of smaller, mechanistically-based studies as a first step in evaluating promising combinations and establishing a mechanistic plan that will inform on the pathways of tolerance.
Principal Investigator:
Doruk Erkan, MD, MPH | Hospital for Special Surgery
Jason Knight, MD, PhD | University of Michigan
A study about the safety of daratumumab in patients with antiphospholipid syndrome (APS), and its effectiveness at reducing the antiphospholipid antibodies that cause APS.
Category:
Autoimmune Disease
|
Specific Category:
|
Status:
Active
Learn more:
Principal Investigator:
William St. Clair, MD | Duke University
The goal of CONTROL-RA is to see how the experimental study drug, VIB4920, affects control of rheumatoid arthritis (RA).
Category:
Autoimmune Disease
|
Specific Category:
Rheumatoid Arthritis
|
Status:
Active
Learn more:
Principal Investigator:
Betty Diamond, MD | Feinstein Institute for Medical Research
David Wofsy, MD | University of California San Francisco School of Medicine
Maria Dall'Era, MD | University of California San Francisco School of Medicine
The goal of the VIBRANT trial is to determine if treating lupus nephritis with VIB4920 in addition to standard therapy is more effective than treating lupus nephritis with standard therapy alone.
Category:
Autoimmune Disease
|
Specific Category:
Lupus
|
Status:
Active
Learn more:
Principal Investigator:
Patrick Nachman, MD | University of Minnesota
Ignacio Sanz, MD | Emory University
REBOOT will test whether a combination of, belimumab and rituximab, is safe and if this combination is more effective at blocking the immune attack on the kidney of patients with Primary Membranous Neuropathy (MN).
Category:
Autoimmune Disease
|
Specific Category:
|
Status:
Active
Learn more:
Principal Investigator:
Jeffrey Cohen, MD | Cleveland Clinic
George Georges, MD | Fred Hutchinson Cancer Research Center
Paolo Muraro, MD, PhD | Imperial College London
BEAT-MS is a clinical trial comparing chemotherapy followed by autologous hematopoietic stem cell transplant (AHSCT) – a type of bone marrow transplantation – to the most effective medicines regularly used to treat relapsing MS.
Category:
Autoimmune Disease
|
Specific Category:
Multiple Sclerosis
|
Status:
Active
Learn more:
Principal Investigator:
David Fox, MD | University of Michigan | Ann Arbor, MI
Dinesh Khanna, MD | University of Michigan | Ann Arbor, MI
BRAVOS is a clinical trial evaluating Brentuximab Vendotin treatment for Diffuse Cutaneous Systemic Sclerosis.
Category:
Autoimmune Disease
|
Specific Category:
Scleroderma
|
Status:
Active
Learn more:
Principal Investigator:
Brett King, MD, PhD | Yale University
The REVEAL study will investigate whether the experimental study medication, AMG714, can bring back normal color to the skin in vitiligo.
Category:
Autoimmune Disease
|
Specific Category:
|
Status:
Completed
Learn more:
Principal Investigator:
Betty Diamond, MD | Feinstein Institute | Manhasset, NY
David Wofsy, MD | University of California San Francisco | San Francisco, CA
The objective of the CALIBRATE study is to determine if treating lupus nephritis with a combination of rituximab (Rituxan®) and cyclophosphamide (Cytoxan®), or a combination of rituximab and cyclophosphamide followed by treatment with belimumab (Benlysta®) is safe and if this drug combination can block the immune system attacks on the kidney.
Category:
Autoimmune Disease
|
Specific Category:
Lupus
|
Status:
Completed
Learn more:
Principal Investigator:
James Krueger, MD, PhD | Rockefeller University | New York, NY
PAUSE is a clinical trial testing the effectiveness of ustekinumab (STELARA ®) followed by an investigational drug, abatacept, for the treatment of psoriasis. The main goal of the study is to determine the efficacy of abatacept to induce prolonged remission.
Category:
Autoimmune Disease
|
Specific Category:
Psoriasis
|
Status:
Completed
Learn more:
Principal Investigator:
Samia Khoury | Harvard Medical School | Boston, MA
ACCLAIM is a Phase II clinical research trial of the safety and efficacy of abatacept in adults with relapsing-remitting multiple sclerosis (RRMS). The study is testing whether abatacept works differently from most other MS treatments, as it is more specific in the immune cells that it targets.
Category:
Autoimmune Disease
|
Specific Category:
Multiple Sclerosis
|
Status:
Completed
Learn more:
Principal Investigator:
Lloyd Mayer, MD | Mount Sinai Medical Center | New York, NY
The purpose of this study is to determine whether Immucothel, a Keyhole Lymphocyte Antigen (KLH) product, can trigger an immune response when ingested orally and create "oral tolerance" to KLH. If not, Immucothel will be tested with another agent to enhance the immune response.
Category:
Autoimmune Disease
|
Specific Category:
|
Status:
Completed
Learn more:
Principal Investigator:
Richard A. Nash | Fred Hutchinson Cancer Research Center | Seattle, WA
The HALT-MS study is investigating an experimental treatment of intensive immunosuppression followed by a transplant of the participant’s own stem cells, to see whether it can stabilize multiple sclerosis. Bone marrow CD34+ stem cells are collected from the participant, and transplanted back into the body following treatment with high doses of chemotherapy drugs. This study is for individuals with relapsing-remitting or progressive-relapsing MS, who have experienced relapses while on other MS treatments.
Category:
Autoimmune Disease
|
Specific Category:
Multiple Sclerosis
|
Status:
Completed
Learn more:
Principal Investigator:
David Wofsy | University of California | San Francisco, CA
Betty Diamond | Feinstein Institute | Manhasset, NY
This study is for people with systemic lupus who have developed complications in their kidneys, called 'lupus nephritis.' The study will determine whether adding the experimental medication abatacept to standard cyclophosphamide therapy is more effective in improving lupus nephritis than standard cyclophosphamide therapy by itself.
Category:
Autoimmune Disease
|
Specific Category:
Lupus
|
Status:
Completed
Learn more:
Principal Investigator:
Jack Antel | Montreal Neurological Institute | Montreal, Quebec | Canada
This study aims to evaluate the safety and tolerability of a 5 mg dose of the study drug, NBI-5788, for treatment of relapsing-remitting multiple sclerosis patients. A prior phase 2 trial conducted with this drug demonstrated suggestive evidence of treatment benefit with a 5 mg dose of NBI-5788.
Category:
Autoimmune Disease
|
Specific Category:
Multiple Sclerosis
|
Status:
Completed
Learn more:
Principal Investigator:
Florian Kern | Institut für Medizinische Immunologie | Berlin, Germany
This study seeks to optimize and standardize an existing assay which allows the T-cell response directed against in transplant recipients who undergo immune tolerance induction. This study employs a rapid laboratory test that would enable the transplant physicians to look at the patient's immune response to this model virus.
Category:
Autoimmune Disease
|
Specific Category:
|
Status:
Completed
Learn more:
Principal Investigator:
Jean Paul Soullilou | Institute de Transplantation | Nantes, France
This trial investigates the landscape of blood T lymphocytes in patients with active forms of multiple sclerosis. The goal of the study is to demonstrate T cell receptor (TCR) patterns that are specific for disease activity at the patient level and then to use this “TCR signature” to follow regulation of auto reactive T cells, particularly during tolerance induction.
Category:
Autoimmune Disease
|
Specific Category:
|
Status:
Completed
Learn more:
