PROCHYMAL® (Human Adult Stem Cells) for the Treatment of Recently Diagnosed Type 1 Diabetes Mellitus (T1DM)

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of PROCHYMAL® (Ex Vivo Cultured Adult Human Mesenchymal Stem Cells) for the Treatment of Recently Diagnosed Type 1 Diabetes Mellitus

The purpose of this study is to establish the safety and efficacy of multiple administrations of PROCHYMAL® in participants recently diagnosed with type 1 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes; Type 1 Diabetes Mellitus; Diabetes Mellitus, Insulin-Dependent; Juvenile Diabetes
• Intervention / Treatment: Drug: PROCHYMAL®; Drug: Placebo

Detailed Description

Diabetes mellitus refers to disorders in which the body has trouble controlling its blood glucose levels. There are two main types of diabetes: type 1 and type 2. Type 1 diabetes mellitus (T1DM), which is being studied in this trial, is an autoimmune disorder in which the body's own immune system attacks and destroys the cells that make insulin. These cells are called beta cells. As beta cells are destroyed, less insulin can be made. This causes blood sugar levels to increase above normal and can cause life-threatening hypo- and hyper-glycemic reactions. For this reason, people with type 1 diabetes must take insulin to help control their blood sugar levels. Over time, poorly controlled diabetes can lead to a variety of serious health conditions, including heart disease, stroke, blindness, amputations, kidney disease, and nerve damage. Insulin is the primary method of controlling diabetes by regulating blood glucose levels, but it may not reverse or prevent disease progression. The active ingredient in PROCHYMAL® is adult human mesenchymal stem cells (MSCs). MSCs have been shown to interact with the immune cells in the body, reducing inflammation and assisting in tissue repair. This study will help determine whether MSCs can protect normal pancreatic tissue from autoimmune attack and repair damaged pancreatic tissue, leading to an increase in insulin production and decrease in circulating blood glucose. The characteristics and biologic activity of PROCHYMAL®, along with a good safety profile in human trials to date, suggest that PROCHYMAL® may be a good candidate for addressing Type 1 Diabetes.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama, Division of Endocrinology & Metabolism
  • California
    • La Jolla, California, United States, 92037
      • Scripps Whittier Diabetes Institute
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Miami, Florida, United States, 33136
      • Diabetes Research Institute
  • Kentucky
    • Lexington, Kentucky, United States, 40502
      • University of Kentucky
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Desert Endocrinology CRC
    • Las Vegas, Nevada, United States, 89101
      • Nevada Alliance Against Diabetes
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Diabetes Care Center
    • Charlotte, North Carolina, United States, 28207
      • American Health Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Clinical Trial Center
    • Dayton, Ohio, United States, 45439
      • Providence Health Partners - Center For Clinical Research
  • Pennsylvania
    • Carlisle, Pennsylvania, United States, 17015
      • Cumberland Valley Endocrinology
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • AM Diabetes & Endocrinology Center
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Optimum Clinical Research, Inc.
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • The Strelitz Diabetes Center, Eastern VA Medical School
  • Wisconsin
    • Madison, Wisconsin, United States, 53717
      • University of Wisconsin Health- West Clinic
    • Milwaukee, Wisconsin, United States, 53226
      • Clinical and Transitional Science Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 33 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant must have a diagnosis of type 1 diabetes mellitus based on the American Diabetes Association (ADA) criteria.
• Participant must be screened between 2 and 20 weeks from initial T1DM diagnosis
• Participants must be between the ages of 12 and 35 (inclusive).
• Participant must have at least one diabetes-related autoantibody present (either GAD or IA-2).
• Participant must have some beta cell function as determined by C-peptide testing (at least 0.2 pmol/mL (0.6 ng/mL) during MMTT.
• Participants must be willing to comply with "intensive diabetes management" as directed by the Investigator with the goal of maintaining blood glucose as close to normal as possible (i.e., glycosylated hemoglobin A1c (HbA1c) value of ≤ 7.0%).
• Participants must be willing to comply with the schedule of study visits and protocol requirements.

Exclusion Criteria:

• Participant has Body Mass Index (BMI) ≥ 30.
• Participant has evidence of retinopathy at baseline.
• Participant has abnormally high lipid levels.
• Participant has abnormal blood pressure.
• Participant has an abnormal serum creatinine.
• Participant has evidence of clinically significant proteinuria.
• Participant has diabetic ketoacidosis.
• Participant is being treated for a severe active infection of any type.
• A female participant who is breast-feeding, pregnant, or intends to become pregnant during the study.
• Participant with clinically relevant uncontrolled medical condition not associated with diabetes (e.g. hematologic, renal, hepatic, neurologic, cardiac, or respiratory).
• Participant has received an investigational drug (not approved by the FDA) for any indication 30 days prior to the screening visit.
• Participant is allergic to bovine or porcine products.
• Participant has evidence of active malignancy or prior history of active malignancy that has not been in remission for at least 5 years.
• Participant has any medical condition, which in the opinion of the Investigator, rendered his/her participation in this study unsuitable.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Intravenous infusion of excipients of PROCHYMAL®
Experimental: Prochymal; PROCHYMAL®	Drug: PROCHYMAL®; Intravenous infusion of ex vivo cultured adult human mesenchymal stem cells; Other Names: ex vivo cultured adult human mesenchymal stem cells; Prochymal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
C-peptide area under the concentration curve (AUC) response (MMTT)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of severe and documented hypoglycemic events	2 years
Peak C-peptide response (MMTT)	2 years
Basal C-peptide response	2 years
Total daily insulin dose (units/kg)	2 years
Glycosylated hemoglobin (HbA1c) levels	2 years
Changes in levels of glutamic acid decarboxylase (GAD) or islet antigen 2 (IA-2) autoantibodies	2 years

Collaborators and Investigators

• Sponsor: Mesoblast, Inc.
• Collaborators: Juvenile Diabetes Research Foundation
• Investigators: Study Director: Mahboob Rahman, MD, Mesoblast, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2008
• Primary Completion (Actual): December 12, 2010
• Study Completion (Actual): December 19, 2011

Study Registration Dates

• First Submitted: June 2, 2008
• First Submitted That Met QC Criteria: June 2, 2008
• First Posted (Estimate): June 4, 2008

Study Record Updates

• Last Update Posted (Actual): December 23, 2021
• Last Update Submitted That Met QC Criteria: December 20, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Insulin; Mesenchymal Stem Cells; Type 1 Diabetes Mellitus; Type 1 Diabetes; Juvenile Diabetes; T1DM; MSCs; Prochymal; Adult Human Stem Cells; Osiris; Diabetes Mellitus, Insulin-Dependent
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Anti-Infective Agents; Antiviral Agents; Anti-Inflammatory Agents; Remestemcel-l
• Other Study ID Numbers: 901

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No