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

Sponsor

Mesoblast, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00690066

Collaborator

Juvenile Diabetes Research Foundation (Other)

Enrollment

Locations

Arms

42.3

Actual Duration (Months)

3.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus Type 1 Diabetes Diabetes Mellitus, Insulin-Dependent Juvenile Diabetes	Drug: PROCHYMAL® Drug: Placebo	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

63 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

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

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 11, 2008

Actual Primary Completion Date :

Dec 12, 2010

Actual Study Completion Date :

Dec 19, 2011

Arms and Interventions

Arm	Intervention/Treatment
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
Placebo Comparator: Placebo Placebo	Drug: Placebo Intravenous infusion of excipients of PROCHYMAL®

Arm

Intervention/Treatment

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

Placebo Comparator: Placebo

Placebo

Drug: Placebo

Intravenous infusion of excipients of PROCHYMAL®

Outcome Measures

Primary Outcome Measures

C-peptide area under the concentration curve (AUC) response (MMTT) [1 year]

Secondary Outcome Measures

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]
Number of severe and documented hypoglycemic events [2 years]
Changes in levels of glutamic acid decarboxylase (GAD) or islet antigen 2 (IA-2) autoantibodies [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama, Division of Endocrinology & Metabolism	Birmingham	Alabama	United States	35294
2	Scripps Whittier Diabetes Institute	La Jolla	California	United States	92037
3	Stanford University	Stanford	California	United States	94305
4	University of Florida	Gainesville	Florida	United States	32610
5	Diabetes Research Institute	Miami	Florida	United States	33136
6	University of Kentucky	Lexington	Kentucky	United States	40502
7	University of Minnesota	Minneapolis	Minnesota	United States	55455
8	Desert Endocrinology CRC	Henderson	Nevada	United States	89052
9	Nevada Alliance Against Diabetes	Las Vegas	Nevada	United States	89101
10	University of North Carolina Diabetes Care Center	Chapel Hill	North Carolina	United States	27599
11	American Health Research, Inc.	Charlotte	North Carolina	United States	28207
12	The Lindner Clinical Trial Center	Cincinnati	Ohio	United States	45219
13	Providence Health Partners - Center for Clinical Research	Dayton	Ohio	United States	45439
14	Cumberland Valley Endocrinology	Carlisle	Pennsylvania	United States	17015
15	AM Diabetes & Endocrinology Center	Bartlett	Tennessee	United States	38133
16	The University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
17	Optimum Clinical Research, Inc.	Salt Lake City	Utah	United States	84102
18	The Strelitz Diabetes Center, Eastern VA Medical School	Norfolk	Virginia	United States	23510
19	University of Wisconsin Health- West Clinic	Madison	Wisconsin	United States	53717
20	Clinical and Transitional Science Institute	Milwaukee	Wisconsin	United States	53226