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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Juvenile Diabetes, Type 1 Diabetes Mellitus, Type 1 Diabetes, Diabetes Mellitus, Insulin-Dependent

Intervention / Treatment
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* Drug: PROCHYMAL®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prochymal<br>PROCHYMAL® | Drug: PROCHYMAL®<br>* Intravenous infusion of ex vivo cultured adult human mesenchymal stem cells<br>* Other names: Prochymal;|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Intravenous infusion of excipients of PROCHYMAL®<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Juvenile Diabetes, Adult Human Stem Cells, Mesenchymal Stem Cells, MSCs, Insulin, Osiris, Prochymal, T1DM, Type 1 Diabetes Mellitus, Type 1 Diabetes, Diabetes Mellitus, Insulin-Dependent