Study Description

Rheumatoid Arthritis (RA) affects adults in the prime of their life and their career with two peaks of onset, the first in the mid-life around the age of forty and the second in the sixties. RA affects women more frequently than men with up to 1% of the population affected. The burden to society includes but is not limited to the potential loss of individuals who are at the peak of their careers themselves who may be affected by RA or who may be responsible for caring for a family member with RA.

This study proposes a double-blind placebo-controlled Phase I cell therapy clinical trial in seropositive, new-onset RA patients (within 2 years of diagnosis) who have high disease activity despite an adequate trial of methotrexate, a Disease Modifying Anti-Rheumatic Drug (DMARD).

The driving hypothesis for this clinical trial is that MSCs will have therapeutic value in restoring immune tolerance. MSCs have the potential to delay or abort onset of full-blown RA by resetting the immune system, inducing immune tolerance and dampening the observed amplification of adaptive immune mechanisms that perpetuate joint inflammation. Multiple RA therapies are available, but none specifically repair autoimmunity; rather most interfere with both autoimmunity and protective host immunity. Most affected require lifelong therapy, rendering RA patients susceptible to infection and malignancy beyond that which RA itself confers. This study will focus on the safety of IV delivery of adult, bone marrow-derived allogeneic MSCs collected from a normal donor and expanded ex vivo. Patients will be randomized to MSCs or placebo and treated with a single infusion of MSCs while remaining on concomitant methotrexate except in the interval immediately after MSC infusion (so as not to damage the infused MSCs).

ELIGIBILITY CRITERIA:

Ages Eligible for Study:           18 Years to 80 Years   (Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  No

Inclusion Criteria:

• 18-80 years
• Recent onset rheumatoid arthritis and have known doctor diagnosis ≤ 1 years and symptoms for ≤ 2 years.
• Patients must have detectable serum auto-antibodies against cyclic citrullinated peptides and/or high titer serum rheumatoid factor at screening or prior to screening.
• Subjects must have active synovitis of at least one joint.
• Patients who have been intolerant or had inadequate response to at least twelve weeks total of methotrexate, ten weeks of which methotrexate must have been dosed at ≥15 mg per week or with low dose steroids (< 10 mg prednisone per day).
• Clinically stable with no significant changes in health status within 2 weeks prior to randomization

Exclusion Criteria:

• Prior use of DMARDs other than non-steroidals, low dose prednisone, hydroxychloroquine and methotrexate
• Use of leflunomide or sulfasalazine for more than 3 days and less than 3 half lives have passed since discontinuing. For leflunomide, wash out is permissible.
• Prior use of Biologic DMARDs
• Presence of active infection
• History of chronic viral infections including Hepatitis B or C or HIV. Treated Hepatitis C is allowed if the viral in non-detectable
• Known chronic liver disease
• Pregnant, breastfeeding, or desire to become pregnant or unwilling to practice birth control during participation in the study and for twelve months after completing the study infusion, unless surgically sterilized or postmenopausal during the study.
• Active tuberculosis (TB) requiring treatment within 3 years prior to baseline
• Latent TB diagnosed during screening that has not been appropriately treated
• History of Cancer requiring chemotherapy within the past 5 years except Human Papillomavirus (HPV) related cervical changes that are not carcinoma in situ.
• Chronic obstructive pulmonary disease or known lung disease except for mild asthma treated with bronchodilators.
• Use of an investigational agent within the 4-week period prior to screen
• If Dimethyl sulfoxide (DMSO) is used in the preparation of MSCs then subjects with known sensitivity to DMSO will be excluded
• History of Transient Ischemic Attack
• History of Cerebrovascular Accident (stroke)
• Clinically significant heart disease (New York Heart Association, class III and class IV).

Study Design:

Allocation: Randomized

Intervention Model: Sequential Assignment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

Study Location(s):

UH Hospitals Cleveland, Cleveland, Ohio, United States, 44106

MetroHealth Medical Center, Cleveland, Ohio, United States, 44109

Study Website:

https://clinicaltrials.gov/ct2/show/NCT03186417?term=NCT03186417&rank=1