A Phase III Study to Investigate if the Study Drug Diamyd Can Preserve Insulin Production and Improve Glycemic Control in Patients Newly Diagnosed With Type 1 Diabetes

NCT05018585 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DIAGNODE-3 (D/P3/21/7)2024-513304-33-00
• Study Type: interventional
• Target: 321
• Locations: 8 countries
• Sites: 48

Brief Summary

The objective of DIAGNODE-3 is to evaluate the efficacy and safety of three intranodal injections of 4 μg of Diamyd also known as retogatein compared to placebo, along with oral Vitamin D supplementation, to preserve endogenous beta cell function and influence glycemic parameters in adolescent and adults recently diagnosed with T1D carrying the HLA DR3-DQ2 haplotype.

Conditions

Type 1 Diabetes Mellitus

Keywords

Diabetes Mellitus; residual beta cell function; HLA DR3-DQ2; Diabetes Mellitus, Type 1; Autoimmune Diseases; Metabolic Disease; Autoimmune Diabetes; Vitamin D; Immune System Diseases; Insulin Dependent Diabetes; rhGAD65; GAD65; GAD-alum; residual c-peptide; T1D; recent-onset T1D; Type 1 Diabetes; HLA; Diamyd; Diabetes; Newly Diagnosed; New onset; DIAGNODE-3; GAD; Diamyd GAD; Intralymphatic injections; Diabetes immunotherapy; Immunotherapy; Antigen-specific; retogatein

Outcome Measures

Primary Outcomes (2)

• Beta cell function

  Change from baseline to Month 15 in C-peptide area under the curve (AUC) mean 0-120 min during a 2-hour mixed meal tolerance test (MMTT)

  Baseline to 15 months

• Glycemic control

  Change from baseline to Month 15 in hemoglobin A1c (HbA1c).

  Baseline to 15 months

Secondary Outcomes (10)

• Change in time in glycemic target range

  Baseline and 15 months

• Proportion of patients with a stimulated 90 min C-peptide level above 0.2 nmol/L (0.6 ng/ml) at Month 15

  Baseline to Month 15

• Proportion of patients with HbA1c <7 % (53 mmol/mol)

  Baseline to Month 15

• Change in exogenous insulin requirements

  Baseline to Month 15

• Change in hypoglycemic episodes per day

  Baseline to Month 15

Study Arms (2)

Diamyd

EXPERIMENTAL

Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (rhGAD65) on Days 0, 30, and 60 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day -30 through Day 90)

Biological: Recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel®; Dietary Supplement: Colecalciferol 2000 IU

Placebo

PLACEBO COMPARATOR

Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo on Days 0, 30, and 60 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day -30 through Day 90)

Dietary Supplement: Colecalciferol 2000 IU; Biological: Placebo

Interventions

Colecalciferol 2000 IU DIETARY_SUPPLEMENT

Colecalciferol (vitamin D3) 2000 IU (equivalent to 50 microgram vitamin D3).

Also known as: Divisun 2000 IU

Diamyd; Placebo

Placebo BIOLOGICAL

Placebo for Diamyd, Alhydrogel® only

Placebo

Recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel® BIOLOGICAL

Recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel®

Also known as: Diamyd

Diamyd

Eligibility Criteria

• Age: 12 Years - 28 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients are eligible to be included in this study only if all of the following criteria apply:
• Must be capable of providing written, signed, and dated informed consent; and for patients who are minors, age-appropriate assent (performed according to local regulations) and parent/caregiver consent.
• Males and females aged ≥12 and \<29 years old at the time of Screening (V1A).
• Diagnosed with T1D (according to the American Diabetes Association \[ADA\] classification) ≤6 months at the time of Screening (V1A).
• Possess the HLA DR3-DQ2 haplotype (all patients will be tested; prior genetic testing results will not be accepted).
• Fasting C-peptide ≥0.12 nmol/L (≥0.36 ng/mL) on at least one occasion prior to randomization.
• (US ONLY): Fasting C-peptide ≥0.12 - ≤1.5 nmol/L (≥0.36 - ≤4.5 ng/mL) on at least one occasion prior to randomization.
• Possess detectable circulating GAD65 antibodies (lowest level of detection defined by the method used by the central laboratory).
• Possess HbA1c levels between 35 to 80 mmol/mol (5.4 to 9.5%) on at least one occasion prior to randomization.
• i. Females of childbearing potential (FOCBP) must agree to avoid pregnancy and have a negative pregnancy test performed at the required study visits.
• FOCBP must agree to use highly effective contraception, during treatment and, until 90 days after the last administration of study medication. Birth control methods, which may be considered as highly effective (e.g., a failure rate of less than 1% per year when used consistently and correctly) include:
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
• Oral.
• Intravaginal.
• Transdermal.

You may not qualify if:

• Patients are not eligible to be included in this study if any of the following criteria apply:
• Participation in any other trial aimed to influence beta cell function from time of diagnosis of T1D.
• Treatment with any oral or non-insulin injectable anti-diabetic medication or other substance used with the intention to preserve beta cell function (e.g., Verapamil, GABA etc.) within 3 months prior to Randomization.
• History of maturity-onset diabetes of the young (MODY).
• Pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased beta cell capacity (e.g., pancreatogenous diabetes).
• Occurrence of DKA or severe hypoglycemia requiring hospitalization in the period of 90 days prior to Randomization (Visit 2).
• Signs or symptoms suggesting very poorly controlled diabetes e.g., ongoing weight loss, polyuria or polydipsia.
• Hematologic condition that would make HbA1c uninterpretable including:
• Hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis.
• Donation of blood or blood products to a blood bank, blood transfusion or participation in a clinical study requiring withdrawal of \>400 mL of blood during the 8 weeks prior to the Screening visit.
• Significant iron deficiency anemia.
• Heart malformations or vaso-occlusive crisis (VOC) leading to increased turnover of erythrocytes.
• (US ONLY) Clinically significant abnormal hematology results at the time of Screening, specifically any of the following: white blood cells: \< 3.5 x 10\^9/L or \>15 x 10\^9/L; platelets: \<124 x 10\^9/ L hemoglobin: \<10.5 g/dL
• Treatment with marketed or over-the-counter Vitamin D at the time of Screening (V1C) and unwilling to abstain from such medication during the 120 days when the patient will be supplemented with the trial-provided Vitamin D. A patient currently taking Vitamin D at the time of Screening (V1C) must be willing to switch to the trial-provided Vitamin D treatment and to administer it per the trial requirements.
• (US ONLY) History of hyperparathyroidism, hypercalcemia and/or nephrolithiasis, unless appropriately treated, or any other contraindication to use of Vitamin D.

Sponsors & Collaborators

• Diamyd Medical AB: lead

Study Sites (60)

Mary and Dick Allen Diabetes Center at Hoag Hospital

Newport Beach, California, 92663, United States

Location

Stanford University School of Medicine Center for Academic Medicine

Palo Alto, California, 94304, United States

Location

UCSD/ Rady Children's Hospital

San Diego, California, 92123, United States

Location

University of Colorado Anschutz Medical Campus, Barbara Davis Center for Childhood Diabetes

Aurora, Colorado, 80045, United States

Location

Diabetes Research Institute (DRI)-University of Miami Leonard M. Miller School of Medicine (UMMSM)

Miami, Florida, 33136, United States

Location

Rocky Mountain Diabetes and Osteoporosis Center

Idaho Falls, Idaho, 83404, United States

Location

University of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

The Joslin Center

Boston, Massachusetts, 02215, United States

Location

Washington University Diabetes Center at Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Hassenfeld Children&#39;s Hospital at NYU Langone Health, Pediatric Diabetes Center

New York, New York, 10016, United States

Location

Amarillo Medical Specialists

Amarillo, Texas, 79124, United States

Location

Diabetes &amp; Glandular Disease Clinic

San Antonio, Texas, 78237, United States

Location

Nemocnice Jihlava, příspěvková organizace

Jihlava, 586 01, Czechia

Location

Institut klinické a experimentální medicíny

Prague, 140 21, Czechia

Location

Fakultní nemocnice v Motole

Prague, 150 06, Czechia

Location

Krajská zdravotní, a.s. - Masarykova nemocnice v Ústí nad Labem, o.z.

Ústí nad Labem, 400 13, Czechia

Location

Liina Viitas OÜ

Pärnu, 80018, Estonia

Location

North-Estonian Regional Hospital

Tallinn, 13419, Estonia

Location

Tartu University Hospital

Tartu, 50406, Estonia

Location

Tartu University Hospital, Children's Clinic

Tartu, 51014, Estonia

Location

Diabetespraxis Dr. Braun

Berlin, 131 87, Germany

Location

Diabetologische Schwerpunktpraxis Dres. Klaus

Dortmund, 441 37, Germany

Location

DZDM - Diabeteszentrum Duisburg Mitte

Duisburg, 470 51, Germany

Location

Justus-Liebig-Universität Gießen

Giessen, 353 92, Germany

Location

Óbudai Egészségügyi Centrum

Budapest, 1036, Hungary

Location

Heim Pál Országos Gyermekgyógyászati Intézet, Diabetológia

Budapest, 1089, Hungary

Location

Észak-Budai Szent János Centrumkórház, Kútvölgyi Kórház, Belgyógyászat

Budapest, 1125, Hungary

Location

Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi, Oktatókórház, Jósa András Oktatókórház, Gyermekosztály

Nyíregyháza, 4400, Hungary

Location

Markusovszky Egyetemi Oktatókórház, Diabetológiai Szakrendelés

Szombathely, 9700, Hungary

Location

CTU Vasculaire Geneeskunde, Locatie Academic Medical Center (AMC)

Amsterdam, 1105 AZ, Netherlands

Location

Albert Schweitzer Ziekenhuis

Dordrecht, 3318 AT, Netherlands

Location

Bethesda Diabetes Research Center te Hoogeveen

Hoogeveen, 7909 AA, Netherlands

Location

Dept. of Nephrology / Dept. of Endocrinology, Leiden University Medical Center (LUMC)

Leiden, 2333 ZA, Netherlands

Location

Vivendia

Nijmegen, 6532 CL, Netherlands

Location

Diabeter Nederland te Rotterdam

Rotterdam, 3011 TA, Netherlands

Location

Uniwersytecki Dziecięcy Szpital Kliniczny im. L. Zamenhofa w Białymstoku, Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdziałem Kardiologii

Bialystok, 15-274, Poland

Location

Uniwersyteckie Centrum Kliniczne, Klinika Pediatrii, Diabetologii i Endokrynologii

Gdansk, 80-952, Poland

Location

SP ZOZ Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Chorób Metabolicznych i Diabetologii

Krakow, 30-688, Poland

Location

NZOZ Przychodnia Specjalistyczna Medica

Lublin, 20-538, Poland

Location

Kliniczny Szpital Wojewódzki nr 2 im. Św. Jadwigi Królowej w Rzeszowie, II Klinika Pediatrii, Endokrynologii i Diabetologii Dziecięcej

Rzeszów, 35-301, Poland

Location

Instytut Diabetologii Sp. z o.o

Warsaw, 02-117, Poland

Location

Panstwowy Instytut Medyczny MSWiA Klinika Chorob Wewnetrznych, Endokrynologii i Diabetologii

Warsaw, 02-507, Poland

Location

Instytut Pomnik - Centrum Zdrowia Dziecka (IPCZD) Oddział Diabetologii

Warsaw, 04-730, Poland

Location

Hospital De Cruces

Barakaldo, 48903, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital de Sant Joan de Déu - Esplugues De Llobregat, Barcelona

Barcelona, 08950, Spain

Location

Hospital Universitari de Girona Dr. Josep Trueta

Girona, 17007, Spain

Location

Complejo Hospitalario Insular de Gran Canaria

Las Palmas, 35016, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital General Universitario de Valencia

Valencia, 46014, Spain

Location

Skånes universitetssjukhus

Malmo, Skåne County, 20502, Sweden

Location

Akademiskt Specialistcentrum, Centrum for Diabetes

Stockholm, Stockholm County, 102 35, Sweden

Location

Barn-och Ungdomscentrum Västerbotten, Norrlands Universitetssjukhus

Umeå, Västerbotten County, 901 85, Sweden

Location

H.K.H Kronprinsessan Victorias Barn-och Ungdomssjukhus, Universitetssjukhuset i Linköping

Linköping, Östergötland County, 581 85, Sweden

Location

Related Publications (1)

• Ludvigsson J, Eriksson L, Nowak C, Teixeira PF, Widman M, Lindqvist A, Casas R, Lind M, Hannelius U. Phase III, randomised, double-blind, placebo-controlled, multicentre trial to evaluate the efficacy and safety of rhGAD65 to preserve endogenous beta cell function in adolescents and adults with recently diagnosed type 1 diabetes, carrying the genetic HLA DR3-DQ2 haplotype: the DIAGNODE-3 study protocol. BMJ Open. 2022 Oct 31;12(10):e061776. doi: 10.1136/bmjopen-2022-061776.

  PMID: 36316084 DERIVED

Related Links

• Study website

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Autoimmune Diseases; Metabolic Diseases; Immune System Diseases

Interventions

Aluminum Hydroxide; Cholecalciferol

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Johnny Ludvigsson, Professor

  Crown Princess Victoria Children´s Hospital and Linköping University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study is a 2-arm, randomized, double-blind, placebo-controlled, multicenter, clinical trial.

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 24, 2021
• Study Start: May 19, 2022
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); NL (6); DE (4); HU (5); PL (8); SE (4); ES (4); CZ (4)