Protege Extension Trial - Long Term Follow Up Trial for Subjects Who Completed the Protege Study (CP-MGA031-01)

An Extension of Study CP-MGA031-01 to Evaluate the Long-Term Efficacy and Safety of Teplizumab (MGA031), a Humanized, FcR Non-Binding, Anti-CD3 Monoclonal Antibody, in Patients With Recent-Onset Type 1 Diabetes Mellitus

The purpose of this study is to assess the long term safety and efficacy in subjects with Type 1 Diabetes Mellitus who completed the Protege Study (CP-MGA031-01).

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Diagnostic test: Blood samples for safety; Behavioral: Patient reported outcome questionnaires; Diagnostic test: Analysis of T-cell subsets

Detailed Description

The primary objective of the extension study is to assess long-term safety, with particular focus on the development of serious adverse events (SAEs), adverse events of special interest (AESIs) including opportunistic infections and lymphoproliferative disease, and other immediately reportable events (IREs), in subjects with recent-onset T1DM who complete CP-MGA031-01.

The secondary objectives of the extension study are to: 1) assess long-term efficacy; 2) evaluate immunological effects(North America only); 3) measure anti-teplizumab antibody levels;4) assess Health Related Quality of Life Questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 219
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta Diabetes Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 37 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Complete Protocol CP-MGA031-01 (i.e., all subjects who complete Study Day 728, regardless of how many doses of study drug are received).
2. Provide written informed consent.

Exclusion Criteria:

None

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double-blind Herold Regimen; Patients who had been assigned to Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.	Diagnostic test: Blood samples for safety; serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies; Behavioral: Patient reported outcome questionnaires; EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.; Diagnostic test: Analysis of T-cell subsets; CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets
Experimental: Double-blind 33.3% Herold Regimen; Patients who had been assigned to 33.3% Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.	Diagnostic test: Blood samples for safety; serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies; Behavioral: Patient reported outcome questionnaires; EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.; Diagnostic test: Analysis of T-cell subsets; CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets
Experimental: Double-blind Curtailed Herold Regimen; Patients who had been assigned to Curtailed Herold Regimen in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.	Diagnostic test: Blood samples for safety; serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies; Behavioral: Patient reported outcome questionnaires; EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.; Diagnostic test: Analysis of T-cell subsets; CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets
Placebo Comparator: Double-blind Placebo; Patients who had been assigned to Placebo in Segment 2 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.	Diagnostic test: Blood samples for safety; serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies; Behavioral: Patient reported outcome questionnaires; EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.; Diagnostic test: Analysis of T-cell subsets; CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets
Experimental: Open-label Herold Regimen; Patients who had been assigned to Herold Regimen in Segment 1 of Study CP-MGA031-01 were enrolled to gather additional safety and efficacy data.	Diagnostic test: Blood samples for safety; serum chemistry, hematology, infection screen, thyroid function, Insulin, hemoglobin A1c,and autoantibodies; Behavioral: Patient reported outcome questionnaires; EQ-5D, Peds QL, Low blood sugar survey, and hospitalization information.; Diagnostic test: Analysis of T-cell subsets; CD3, CD4, CD8, CD19, CD3+ CD16+ CD56+ subsets; CD3-CD16+ CD56+ subsets; CD4+CD25+, CD8+CD25+, CD4+CD69+, CD8+CD69+, CD4+CD40+ subsets CD4+ and CD8+CD25+FoxP3+Treg Subsets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Number of Participants Who Experience an Adverse Event, Serious Adverse Event or Adverse Event of Special Interest.	Duration of study participation up to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.		Month 6
Proportion of Subjects in Segment 2 With Both a Total Daily Insulin Dose of Less Than 0.5 U/kg/Day and Hemoglobin A1c (HbA1c) Level of Less Than 6.5%.		Month 12
Proportion of Subjects With HbA1c <6.5%		Month 6
Mean HbA1c at 6 Months		6 months
Mean HbA1c at 12 Months		Month 12
C-peptide Area Under the Curve (AUC) at 6 Months	This outcome measure summarizes the mean and standard deviation of the observed value.	Month 6
C-peptide AUC at 12 Months	This outcome measure summarizes the mean and standard deviation of the observed value.	Month 12
Total Daily Insulin Usage at 6 Months		Month 6
Total Daily Insulin Usage at 12 Months		Month 12
Mean Values for Participant-reported Outcomes on the 5-dimension European Quality of Life Questionnaire. (EQ-5D)	The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from "no problems", "some problems", and "extreme problems". The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life.	Month 6
Mean Values for Participant-reported Outcomes on the EQ-5D	The EQ-5D is a self-reported survey that measures quality of life across 5 domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is scored on a 3-level severity ranking that ranges from "no problems", "some problems", and "extreme problems". The lowest possible score is 5 and the highest possible score is 15. Lower scores indicate better quality of life.	Month 12
Pediatric Quality of Life Questionnaire Total Score	The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed.	Month 6
Pediatric Quality of Life Questionnaire Total Score	The 23-item PEDs QL generic core scales were designed to measure the core dimensions of health (physical, emotional, social and school functioning). Answers are scored from 0 meaning never to 4 meaning almost always. Lower scores indicated higher quality of life. Items on the questionnaire were reversely scored and linearly transformed to a 0-100 scale, so that higher scores indicated better patient reported outcome. The mean was computed as the sum of the items over the number of items answered (to account for missing data). If more than 50% of the items in the scale were missing, the score was not computed.	Month 12
Percentage of Cells by Immunophenotype		Month 6
Human Anti-human Antibody (HAHA) Levels	Patients with HAHA levels > 0.	Month 6 and 12

Collaborators and Investigators

• Sponsor: MacroGenics
• Collaborators: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: March 26, 2009
• First Posted (Estimated): March 27, 2009

Study Record Updates

• Last Update Posted (Actual): August 9, 2023
• Last Update Submitted That Met QC Criteria: July 19, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Monoclonal antibody; Type 1 Diabetes Mellitus; T1DM; Teplizumab; Protege; MGA031; MacroGenics
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: CP-MGA031-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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