Diamyd Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes

NCT03345004 | Completed Phase 2 Results DMC

• 2 other identifiers: DIAGNODE-2 (D/P2/17/6)2017-001861-25
• Study Type: interventional
• Target: 109
• Locations: 4 countries
• Sites: 18

Brief Summary

The objective of DIAGNODE-2 is to evaluate the efficacy of Diamyd compared to Placebo, upon administration directly into a lymph node in combination with an oral vitamin D/Placebo regimen, in terms of preserving endogenous insulin secretion as measured by C-peptide.

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Autoimmune Diseases; Metabolic Disease; Glucose Metabolism Disorders; Immune System Diseases; Endocrine System Diseases; Juvenile Diabetes; Insulin Dependent Diabetes; Autoimmune Diabetes; Vitamin D; Physiological Effects of Drugs

Keywords

Diamyd; Diabetes; Juvenile Diabetes; Diabetes Type 1; Type 1 Diabetes; Autoimmune Diabetes; Insulin Dependent Diabetes; Type 1 Diabetes Mellitus; rhGAD65; GAD65; Diabetes Mellitus; Diabetes Mellitus Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Vitamin D; Vitamins; Micronutrients; Cholecalciferol; Ergocalciferols

Outcome Measures

Primary Outcomes (1)

• Change in Stimulated C-peptide During a MMTT

  Change in C-peptide between Baseline and 15 Months. C-peptide was measured by Area Under the Curve \[AUC\] at 0-120 min during a Mixed Meal Tolerance Test (MMTT) and divided by 120 min. The results are given as the ratio (back-transformed from log-scale) between 15 Months and Baseline as predicted by the MMRM (Mixed Model Repeated Measures) model.

  Baseline and 15 months

Secondary Outcomes (20)

• Change in IDAA1c

  Baseline and 15 months

• Change in HbA1c

  Baseline and 15 months

• Change in Insulin Consumption

  Baseline and 15 months

• Change in Glycemic Variability/Fluctuations

  Screening and 15 months

• Percentage of Patients With IDAA1c ≤ 9

  15 months

Study Arms (2)

Active arm

ACTIVE COMPARATOR

Patients will be assigned to receive i) three (3) intralymphatic injections with Recombinant human Glutamic Acid Decarboxylase adsorbed to Alhydrogel (Diamyd) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)

Biological: Diamyd; Dietary Supplement: Vitamin D

Placebo arm

PLACEBO COMPARATOR

Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)

Biological: Placebo for Diamyd; Dietary Supplement: Placebo for Vitamin D

Interventions

Diamyd BIOLOGICAL

Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD65)

Also known as: GAD-alum

Active arm

Vitamin D DIETARY_SUPPLEMENT

Oil suspension of Vitamin D

Active arm

Placebo for Diamyd BIOLOGICAL

Alhydrogel® only

Placebo arm

Placebo for Vitamin D DIETARY_SUPPLEMENT

Placebo oil suspension for Vitamin D

Placebo arm

Eligibility Criteria

• Age: 12 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Informed consent given by patients and/or patient's parent(s) or legal acceptable representative(s) (guardian(s)) according to national regulations
• Type 1 Diabetes (T1D) according to the Amercian Diabetes Association (ADA) classification diagnosed ≤6 months at the time of screening
• Age: ≥12 and \<25 years old
• Fasting C-peptide ≥0.12 nmol/L (0.36 ng/ml) on at least one occasion (maximum 2 tests on different days within a period of 2 weeks)
• Positive for Glutamic Acid Decarboxylase isoform 65 (GAD65A) but \< 50 000 IU/ml
• Females must agree to avoid pregnancy and have a negative urine pregnancy test. Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of Diamyd. Adequate contraception is as follows:
• For females of childbearing potential:
• oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
• combined (estrogen and progestogen containing)
• oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
• intrauterine device
• intrauterine hormone-releasing system (for example, progestin-releasing coil)
• bilateral tubal occlusion
• vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
• male partner using condom

You may not qualify if:

• Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
• Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
• Treatment with any oral or injected anti-diabetic medications other than insulin
• A history of anemia or significantly abnormal hematology results at screening
• A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
• Clinically significant history of acute reaction to vaccines or other drugs in the past
• Treatment with any vaccine, including influenza vaccine, within 4 months prior to planned first study drug dose or planned treatment with any vaccine up to 4 months after the last injection with study drug.
• Participation in other clinical trials with a new chemical entity within the previous 3 months
• Inability or unwillingness to comply with the provisions of this protocol
• A history of alcohol or drug abuse
• A significant illness other than diabetes within 2 weeks prior to first dosing
• Known HIV or hepatitis
• Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior to the Diamyd/placebo treatment)
• Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study
• Deemed by the investigator not being able to follow instructions and/or follow the study protocol

Sponsors & Collaborators

• Diamyd Medical AB: lead

Study Sites (18)

Diabetes Centre, Institute of Clinical and Experimental Medicine

Prague, 14021, Czechia

Location

Department of Paediatrics, University Hospital Motol

Prague, 15006, Czechia

Location

Diabeter Rotterdam

Rotterdam, 3011 TA, Netherlands

Location

Adult and Pediatrics Endocrinology and Diabetology, Hospital Universitario Cruces

Barakaldo, 48903, Spain

Location

Adult Endocrinology and Diabetology, Hospital vall D' Hebrón

Barcelona, 08035, Spain

Location

Pediatrics Endocrinology and Diabetology, Hospital Vall D'Hebrón

Barcelona, 08035, Spain

Location

Adult Endocrinology and Diabetology, Hospital Ramón y Cajal

Madrid, 28033, Spain

Location

Adult Endocrinology and Diabetology, Hospital Carlos Haya

Málaga, 29009, Spain

Location

Pediatrics Endocrinology and Diabetology, Hospital Materno-Ifantil

Málaga, 29011, Spain

Location

Adult Endocrinology and Diabetology, Hospital Macarena

Seville, 41009, Spain

Location

Pediatrics Endocrinology and Diabetology, Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Adult and Pediatrics Endocrinology and Diabetology, Hospital Miguel Servet

Zaragoza, 50009, Spain

Location

Barn- och Ungdomskliniken, Universitetssjukhuset

Linköping, 58185, Sweden

Location

Endokrinmedicinska kliniken. Universitetssjukhuset

Linköping, 58185, Sweden

Location

Barn-och Ungdomsmedicinmottagningen and Endokrinmottagningen, Skånes Universitetssjukhus

Malmo, 20502, Sweden

Location

Barn- och ungdomskliniken, Uddevalla Sjukhus

Uddevalla, 45180, Sweden

Location

Diabetesmottagningen, Uddevalla Sjukhus

Uddevalla, 45180, Sweden

Location

Barnmottagningen, Norrlands Universitetssjukhus

Umeå, 901 85, Sweden

Location

Related Publications (5)

• Ludvigsson J, Wahlberg J, Casas R. Intralymphatic Injection of Autoantigen in Type 1 Diabetes. N Engl J Med. 2017 Feb 16;376(7):697-699. doi: 10.1056/NEJMc1616343. No abstract available.

  PMID: 28199812 BACKGROUND

• Ludvigsson J, Tavira B, Casas R. More on Intralymphatic Injection of Autoantigen in Type 1 Diabetes. N Engl J Med. 2017 Jul 27;377(4):403-5. doi: 10.1056/NEJMc1703468. No abstract available.

  PMID: 28745988 BACKGROUND

• Puente-Marin S, Dietrich F, Achenbach P, Barcenilla H, Ludvigsson J, Casas R. Intralymphatic glutamic acid decarboxylase administration in type 1 diabetes patients induced a distinctive early immune response in patients with DR3DQ2 haplotype. Front Immunol. 2023 Feb 2;14:1112570. doi: 10.3389/fimmu.2023.1112570. eCollection 2023.

  PMID: 36817467 DERIVED

• Nowak C, Lind M, Sumnik Z, Pelikanova T, Nattero-Chavez L, Lundberg E, Rica I, Martinez-Brocca MA, Ruiz de Adana M, Wahlberg J, Hanas R, Hernandez C, Clemente-Leon M, Gomez-Gila A, Ferrer Lozano M, Sas T, Pruhova S, Dietrich F, Puente-Marin S, Hannelius U, Casas R, Ludvigsson J. Intralymphatic GAD-Alum (Diamyd(R)) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2644-2651. doi: 10.1210/clinem/dgac343.

  PMID: 35665810 DERIVED

• Ludvigsson J, Sumnik Z, Pelikanova T, Nattero Chavez L, Lundberg E, Rica I, Martinez-Brocca MA, Ruiz de Adana M, Wahlberg J, Katsarou A, Hanas R, Hernandez C, Clemente Leon M, Gomez-Gila A, Lind M, Lozano MF, Sas T, Samuelsson U, Pruhova S, Dietrich F, Puente Marin S, Nordlund A, Hannelius U, Casas R. Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial. Diabetes Care. 2021 Jul;44(7):1604-1612. doi: 10.2337/dc21-0318. Epub 2021 May 21.

  PMID: 34021020 DERIVED

Related Links

• Information regarding the clinical trial

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Autoimmune Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Immune System Diseases; Endocrine System Diseases

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Director of Clinical Development
• Organization: Diamyd Medical AB

clinicaltrials@diamyd.com

+46 (0) 8 661 00 26

Study Officials

• Johnny Ludvigsson, MD, Prof

  Universitetssjukhuset i Linköping

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: November 1, 2017
• First Posted: November 17, 2017
• Study Start: December 20, 2017
• Primary Completion: July 13, 2020
• Study Completion: April 27, 2021
• Last Updated: January 9, 2023
• Results First Posted: January 9, 2023

Record last verified: 2022-04

Locations

SE (6); NL (1); ES (9); CZ (2)