Mesenchymal Stem Cells in Early Rheumatoid Arthritis

NCT03186417 | Terminated Phase 1 FDA Drug

• 2 other identifiers: IRB16-00587R21AR069226
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This is a prospective, multicenter, double-blind, placebo controlled interventional study to evaluate the safety and efficacy of allogeneic mesenchymal stem cells (MSCs) in 20 patients with new onset Rheumatoid Arthritis (RA). The study is a single dose, phase I clinical trial and is the first time that this product will be infused in RA patients. The study duration is approximately fourteen months from time of screening to completion. Research hypothesis: The investigators hypothesize that when administered therapeutically, MSCs will induce healthy immune responses and will reduce RA disease activity. This study is primarily focused on demonstrating the safety of this approach.

Conditions

Rheumatoid Arthritis

Keywords

Arthritis, Rheumatoid, Stem Cells, Mesenchymal, Autoimmune

Outcome Measures

Primary Outcomes (4)

• Safety assessed by dose limiting toxicity (DLT)

  • In addition, a DLT will be assigned if through 14 days after the infusion any grade 3-4 adverse event for pulmonary, cardiac, renal, oral mucosal or hepatic, and grade 4 adverse events for other organs occurred per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

  14 days following infusion

• Safety assessed by dose limiting toxicity

  • A DLT is triggered by occurrence through 48 hours after infusion of grade ≥2 infusion-related allergic toxicities, which include rash, flushing, urticaria, dyspnea, fever ≥38°C (≥100.4°F) as scored according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events (CTCAE) version 4.03.

  48 hours following infusion

• Safety assessed by change in spirometry

  • Changes in spirometry following infusion compared to baseline

  30 minutes following infusion

• Safety assessed by all adverse events

  • Incidence and severity of adverse events

  52 weeks following infusion

Secondary Outcomes (2)

• Change in patient reported outcomes

  Up to day 28 after infusion

• DAS28-CRP

  Week 52

Study Arms (3)

Cohort 1

EXPERIMENTAL

2 million human MSC (hMSC)/kg infusion versus placebo infusion

Biological: 2 million hMSC/kg; Biological: placebo

Cohort 2

EXPERIMENTAL

4 million hMSC/kg infusion versus placebo infusion

Biological: 4 million hMSC/kg; Biological: placebo

Cohort 3

EXPERIMENTAL

6 million hMSC/kg infusion versus placebo infusion

Biological: 6 million hMSC/kg; Biological: placebo

Interventions

2 million hMSC/kg BIOLOGICAL

2 million hMSCs/kg infusion

Cohort 1

4 million hMSC/kg BIOLOGICAL

4 million hMSC/kg infusion

Cohort 2

6 million hMSC/kg BIOLOGICAL

6 million hMSC/kg infusion

Cohort 3

placebo BIOLOGICAL

placebo infusion

Cohort 1; Cohort 2; Cohort 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years
• Recent onset rheumatoid arthritis and have known doctor diagnosis ≤ 2 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

You may not qualify if:

• 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), unless there has been no CVA for \> or = 1 year after the resolution of the underlying cause of the CVA

Sponsors & Collaborators

• MetroHealth Medical Center: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (2)

UH Hospitals Cleveland

Cleveland, Ohio, 44106, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Arthritis

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Nora singer, MD

  MetroHealth Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Model Details: This is a dose escalation study using three groups (or cohorts) of patients randomly assigned within treatment groups to MSCs or placebo. The first group will consist of 5 patients who receive MSCs and one patient who receives placebo, the second and third group will consist of five patients each who receive MSCs and two patients who receive placebo. The three doses are 2 million hMSCs/kg (Cohort 1), 4 million hMSCs/kg (Cohort 2), and 6 million hMSCs/kg (Cohort 3) and placebo control of normal saline.

Study Record Dates

• First Submitted: June 12, 2017
• First Posted: June 14, 2017
• Study Start: December 15, 2017
• Primary Completion: April 30, 2023
• Study Completion: May 31, 2023
• Last Updated: June 23, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)