Efficacy and Safety Study of DiaPep277 in Newly Diagnosed Type 1 Diabetes Adults (DIA-AID2)

A Phase 3, Multinational, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Investigate the Clinical Efficacy and Safety of DiaPep277 in Newly Diagnosed Type 1 Diabetes Subjects

This study will look at the treatment effect of DiaPep277 on preservation of beta-cell function, as defined by meal-stimulated secretion of insulin. DiaPep277 is a peptide that changes the way the immune system behaves, stopping its attack on the beta-cells.

Adults (>20 years) with newly diagnosed (<6 months) type 1 diabetes will be treated with 10 injections of DiaPep277 or Placebo over a 2-year treatment and follow-up period.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: DiaPep277; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 475
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Universitatsklinik fur Innere Medzin I, Landeskrankenhaus
  • Vienna, Austria, 1030
    • Rudolfstiftung Hospital
• Belarus
  • Minsk, Belarus, 220013
    • Endocrinological Unit 1st City Clinical Hospital
  • Minsk, Belarus, 220013
    • Republican center of Medical Rehabilitation and Balneotherapy
  • Minsk, Belarus, 220029
    • Health Institution City Endocrinological Dispensary
  • Minsk, Belarus, 220096
    • Belarusian Medical Academy of Postgraduate Education
  • Mogilov, Belarus, 212030
    • Health Institution Mogilev Diagnostic Center
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2H 0K2
      • LMC Endocrinology Centres
  • Ontario
    • Oakville, Ontario, Canada, L6H 3P1
      • LMC Endocrinology Centres
    • Toronto, Ontario, Canada, M4R 2G4
      • LMC Endocrinoly Centres
• Czech Republic
  • Prague, Czech Republic, 10035
    • Fakultni nemocnice Kralovske Vinohrady - II. internal department
  • Prague, Czech Republic, 4140
    • IKEM/Diabetes Centre/Videnska
• Finland
  • Oulu, Finland, 90220
    • Tutkimusyksikko
• Germany
  • Dusseldorf, Germany, 40225
    • DDZ Studienzentrum Deutsches Diabetes Zentrum
  • Giessen, Germany, 35392
    • Universitätsklinikum Gießen
  • Hannover, Germany, 30173
    • Diabetes Centre for Children and Adolescents, Kinderkrankenhaus auf der Bult
  • Munchen, Germany, 80804
    • Institut für Diabetesforschung an der Klinik und Hochschulambulanz für Kinder- und Jugendmedizin
  • Munster, Germany, 48145
    • Institut für Diabetesforschung Münster GmbH
• Hungary
  • Szeged, Hungary, H-6700
    • University of Szeged Faculty of Medicin
  • Veszprem, Hungary, 8200
    • Veszprem Megyei Csolnoky Ferenc Korhaz es Rendelointezet Diabetologia Centrum
  • Zalaegerszeg, Hungary, 9000
    • Zala Megyei Korhaz es Rendelointezet Diabetologia Centrum
• Israel
  • Beer Sheva, Israel, 84101
    • Soroka University Medical Center
  • Beer Sheva, Israel, 84101
    • Diabetes Clinic Soroka University
  • Haifa, Israel, 31096
    • Rambam Medical Cent
  • Holon, Israel
    • Wolfson Medical Center
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Petach-Tiqva, Israel, 49202
    • Institute for Endocrinology and Diabetes Schneider Children's MC
• Italy
  • Palermo, Italy, 90127
    • . Endocrinologia e Malattie Metaboliche, Dipartimento biomedico di medicina interna e specialistica, Ex Istituto di clinica medica, Università di Palerm
  • Rome, Italy, 00128
    • Dept. of Endocrinology and Diabetes University Campus Bio-Medico
  • Rome, Italy, 00161
    • University La Sapienza, Policlinico Umberto I
• Lithuania
  • Jonava, Lithuania, 55201
    • Private Clinic JSC 'Kristavita'
  • Kaunas, Lithuania, 50009
    • Kaunas Medical University Hospital
  • Vilnius, Lithuania, 07156
    • Public Institution 'Seskines Outpatient Clinic'
  • Vilnius, Lithuania, 08661
    • Vilnius Medical University Hospital, Santariskiu Clinic's
• Poland
  • Lodz, Poland, 93-338
    • NZOZ OmniMed
• Russian Federation
  • Chelyabinsk, Russian Federation, 454021
    • State Educational Institution for Additional Professional Education (SEIAPE) "Ural State Medical
  • Kemerovo, Russian Federation, 650066
    • Kemerovo Regional Clinical Hospital
  • Moscow, Russian Federation, 117036
    • Endocrinological scientific center of Rosmedtechnology
  • Moscow, Russian Federation, 125367
    • SEIAPE Endocrinology and Diabetology
  • Moscow, Russian Federation, 127644
    • City Clinical Hospital #81, Endocrinology Department
  • Moscow, Russian Federation, 140091
    • Clinic of New Medical Technology, LLC
  • Nizhni Novgorod, Russian Federation, 603126
    • State Healthcare Institution (SHI) "Nizhegorodskaya
  • Perm, Russian Federation, 614990
    • State Healthcare Institution Perm Region Clinical Hospital
  • Samara, Russian Federation, 443067
    • Limited Liability Company (LLC), Diabetes Center
  • St Petersburg, Russian Federation, 197022
    • State Educational Institution of Higher Professional Education
  • St. Petersburg, Russian Federation, 194354
    • St. Petersburg State Healthcare Institution
  • Tomsk, Russian Federation, 634050
    • Siberian State Medical University of Roszdrav
• Spain
  • Las Palmas de Gran Canaria, Spain, 35016
    • Complejo Hospitalario Universitario Insular Materno-Infantil
  • Lleida, Spain, 25198
    • Hospital Universitari Arnau de Vilanova
• United States
  • California
    • Los Gatos, California, United States, 95032
    • Modesto, California, United States, 95355
      • Sutter Gold Medical Foundation
    • San Diego, California, United States, 92120
      • San Diego Clinical Trials
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Outpatient Pavilion
    • Denver, Colorado, United States, 80209
      • Creekside Endocrine Associates, Inc.
  • District of Columbia
    • Washington, District of Columbia, United States, 20037
      • George Washington University Medical Faculty Associates
  • Florida
    • Aventura, Florida, United States, 33180
      • Innovative Medical Research of South Florida Inc.
    • DeLand, Florida, United States, 32720
    • Orlando, Florida, United States, 32825
      • Orlando Diabetes & Endocrine Specialists, P.A.
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Endocrine Associates
    • Tampa, Florida, United States, 33613
      • Diabetes and Hormonal Disease Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Atlanta Diabetes Associates
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Kentucky Diabetes Endocrinology Center
  • Missouri
    • St. Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Palm Medical Research Center
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Soutwest Clinical Research Center, LLC
  • North Carolina
    • Ashville, North Carolina, United States, 28803
      • Mountain Diabetes and Endocrine Center
    • Durham, North Carolina, United States, 27703
      • University of North Carolina Diabetes Care Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center, The Christ Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Clinical Research & Technology Center
  • Tennessee
    • Bartlett, Tennessee, United States, 38133
      • AM Diabetes & Endocrinology Center
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Institute Of Dallas
    • San Antonio, Texas, United States, 78229
      • Cetero Research
  • Washington
    • Spokane, Washington, United States, 99208
      • Northside Internal Medicine Associates, PS
    • Tacoma, Washington, United States, 98405
      • Multicare Specialties Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• clinical diagnosis of type 1 diabetes within last 6 months
• Age 20-45 years
• fasting basal C-peptide equal or greater than 0.22 nmol/L, lower than 0.8 nmol/L
• BMI between 17 and 30 at screening

Exclusion Criteria:

• Significant disease or condition other than type 1 diabetes
• Diabetes-related complications
• Ongoing treatment with immunosuppressive or immunomodulating agents including chronic corticosteroids

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: DiaPep277; Administration of 1 mg DiaPep277®, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.	Drug: DiaPep277; 1.0 mg dose in 0.5 mL of solution
PLACEBO_COMPARATOR: Placebo; Administration of placebo, subcutaneously (s.c.) in the upper arm at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months, for a total of 10 administrations.	Drug: Placebo; 40 mg mannitol in 0.5 mL of solution. Dosing: 0, 1, 3, 6, 9, 12, 15, 18, 21, 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glucagon-Stimulated C-Peptide AUC at 24 Months	Change in Beta-cell function, measured as stimulated C-peptide secretion 0, 2, 6, 10 and 20 minutes post administration [area under the curve (AUC), 0-20 minutes] at baseline and 24 months, during a glucagon stimulation test (GST). The change in AUC was calculated per patient by subtracting the baseline AUC from the 24 month AUC.	Baseline and 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects That Achieve Good Glycemic Control: HbA1c<7%	The percentage of subjects achieving good glycemic control, i.e. an HbA1c <7% at study end (Month 25). If HbA1c was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with an HbA1c ≤ 7% at study end.	24 and 25 months
Frequency of Hypoglycemic Events	Total number of days with at least one hypoglycemic event recorded	Baseline to 25 Months
Mean Number of Days With at Least One Hypoglycemic Event		Baseline to 25 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Requiring a Daily Insulin Dose ≤ 0.5 IU/kg at End of Study	Percentage of subjects requiring a daily insulin dose ≤ 0.5 IU/kg at end of study (25 Months). If insulin dose was missing at Month 25, but the Month 24 value was available, then the Month 24 value was used to calculate the percentage of subjects with a daily insulin dose ≤ 0.5 IU/kg at study end.	24 and 25 months

Collaborators and Investigators

• Sponsor: Andromeda Biotech Ltd.
• Investigators: Principal Investigator: Thomas Linn, MD, University of Gießen; Principal Investigator: Paolo P Pozzilli, MB, BS, MD, University Campus Bio-Medico, Rome; Principal Investigator: Philip Raskin, MD, UT Southwestern Medical Center, Dallas

Publications and helpful links

General Publications

• Huurman VA, van der Meide PE, Duinkerken G, Willemen S, Cohen IR, Elias D, Roep BO. Immunological efficacy of heat shock protein 60 peptide DiaPep277 therapy in clinical type I diabetes. Clin Exp Immunol. 2008 Jun;152(3):488-97. doi: 10.1111/j.1365-2249.2008.03656.x. Epub 2008 Apr 16.
• Huurman VA, Decochez K, Mathieu C, Cohen IR, Roep BO. Therapy with the hsp60 peptide DiaPep277 in C-peptide positive type 1 diabetes patients. Diabetes Metab Res Rev. 2007 May;23(4):269-75. doi: 10.1002/dmrr.691.
• Schloot NC, Meierhoff G, Lengyel C, Vandorfi G, Takacs J, Panczel P, Barkai L, Madacsy L, Oroszlan T, Kovacs P, Suto G, Battelino T, Hosszufalusi N, Jermendy G. Effect of heat shock protein peptide DiaPep277 on beta-cell function in paediatric and adult patients with recent-onset diabetes mellitus type 1: two prospective, randomized, double-blind phase II trials. Diabetes Metab Res Rev. 2007 May;23(4):276-85. doi: 10.1002/dmrr.707.
• Raz I, Avron A, Tamir M, Metzger M, Symer L, Eldor R, Cohen IR, Elias D. Treatment of new-onset type 1 diabetes with peptide DiaPep277 is safe and associated with preserved beta-cell function: extension of a randomized, double-blind, phase II trial. Diabetes Metab Res Rev. 2007 May;23(4):292-8. doi: 10.1002/dmrr.712.
• Eldor R, Kassem S, Raz I. Immune modulation in type 1 diabetes mellitus using DiaPep277: a short review and update of recent clinical trial results. Diabetes Metab Res Rev. 2009 May;25(4):316-20. doi: 10.1002/dmrr.942.
• Raz I, Elias D, Avron A, Tamir M, Metzger M, Cohen IR. Beta-cell function in new-onset type 1 diabetes and immunomodulation with a heat-shock protein peptide (DiaPep277): a randomised, double-blind, phase II trial. Lancet. 2001 Nov 24;358(9295):1749-53. doi: 10.1016/S0140-6736(01)06801-5.
• Elias D, Avron A, Tamir M, Raz I. DiaPep277 preserves endogenous insulin production by immunomodulation in type 1 diabetes. Ann N Y Acad Sci. 2006 Oct;1079:340-4. doi: 10.1196/annals.1375.052.
• Nussbaum G, Zanin-Zhorov A, Quintana F, Lider O, Cohen IR. Peptide p277 of HSP60 signals T cells: inhibition of inflammatory chemotaxis. Int Immunol. 2006 Oct;18(10):1413-9. doi: 10.1093/intimm/dxl074. Epub 2006 Aug 7.
• Fischer B, Elias D, Bretzel RG, Linn T. Immunomodulation with heat shock protein DiaPep277 to preserve beta cell function in type 1 diabetes - an update. Expert Opin Biol Ther. 2010 Feb;10(2):265-72. doi: 10.1517/14712590903555176.

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): October 1, 2014

Study Registration Dates

• First Submitted: April 13, 2010
• First Submitted That Met QC Criteria: April 13, 2010
• First Posted (ESTIMATE): April 14, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 26, 2016
• Last Update Submitted That Met QC Criteria: April 19, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Diabetes; immunomodulation; autoimmune; beta-cells
• 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: DiaPep277-1001