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

NCT ID: NCT03345004

Last Updated: 2023-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-20
• Study Completion Date: 2021-04-27

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.

Detailed Description

The study is a 2-arm, randomized, double-blind, placebo-controlled, multicenter, clinical trial. Eligible patients will receive injections of Diamyd/placebo into an inguinal lymph gland at three occasions, with one month intervals in combination with an oral vitamin D/placebo regimen (starting 1 month ahead of injections) during 4 months. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period. The patients will be followed in a blinded manner for a total of 15 months. All patients that have not performed the 15 months visit when the updated protocol is implemented, will be asked to participate in the Extension Study Period which includes an additional visit at month 24.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active arm

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)

Group Type: ACTIVE_COMPARATOR

Diamyd

Intervention Type: BIOLOGICAL

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

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Oil suspension of Vitamin D

Placebo arm

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)

Group Type: PLACEBO_COMPARATOR

Placebo for Diamyd

Intervention Type: BIOLOGICAL

Alhydrogel® only

Placebo for Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Placebo oil suspension for Vitamin D

Interventions

Diamyd

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

Intervention Type: BIOLOGICAL

Vitamin D

Oil suspension of Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Placebo for Diamyd

Alhydrogel® only

Intervention Type: BIOLOGICAL

Placebo for Vitamin D

Placebo oil suspension for Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

GAD-alum

Eligibility Criteria

Inclusion Criteria

1. Informed consent given by patients and/or patient's parent(s) or legal acceptable representative(s) (guardian(s)) according to national regulations

2. Type 1 Diabetes (T1D) according to the Amercian Diabetes Association (ADA) classification diagnosed ≤6 months at the time of screening

3. Age: ≥12 and <25 years old

4. 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)

5. Positive for Glutamic Acid Decarboxylase isoform 65 (GAD65A) but < 50 000 IU/ml

6. 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:

1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives

2. combined (estrogen and progestogen containing)

3. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation

4. intrauterine device

5. intrauterine hormone-releasing system (for example, progestin-releasing coil)

6. bilateral tubal occlusion

7. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)

8. male partner using condom

9. abstinence from heterosexual intercourse

For males of childbearing potential:

1. condom (male)

2. abstinence from heterosexual intercourse

Exclusion Criteria

1. Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)

2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)

3. Treatment with any oral or injected anti-diabetic medications other than insulin

4. A history of anemia or significantly abnormal hematology results at screening

5. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles

6. Clinically significant history of acute reaction to vaccines or other drugs in the past

7. 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.

8. Participation in other clinical trials with a new chemical entity within the previous 3 months

9. Inability or unwillingness to comply with the provisions of this protocol

10. A history of alcohol or drug abuse

11. A significant illness other than diabetes within 2 weeks prior to first dosing

12. Known HIV or hepatitis

13. 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)

14. 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

15. Deemed by the investigator not being able to follow instructions and/or follow the study protocol

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Diamyd Medical AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johnny Ludvigsson, MD, Prof

Role: PRINCIPAL_INVESTIGATOR

Universitetssjukhuset i Linköping

Locations

Diabetes Centre, Institute of Clinical and Experimental Medicine

Prague, , Czechia

Department of Paediatrics, University Hospital Motol

Prague, , Czechia

Diabeter Rotterdam

Rotterdam, , Netherlands

Adult and Pediatrics Endocrinology and Diabetology, Hospital Universitario Cruces

Barakaldo, , Spain

Adult Endocrinology and Diabetology, Hospital vall D' Hebrón

Barcelona, , Spain

Pediatrics Endocrinology and Diabetology, Hospital Vall D'Hebrón

Barcelona, , Spain

Adult Endocrinology and Diabetology, Hospital Ramón y Cajal

Madrid, , Spain

Adult Endocrinology and Diabetology, Hospital Carlos Haya

Málaga, , Spain

Pediatrics Endocrinology and Diabetology, Hospital Materno-Ifantil

Málaga, , Spain

Adult Endocrinology and Diabetology, Hospital Macarena

Seville, , Spain

Pediatrics Endocrinology and Diabetology, Hospital Virgen del Rocío

Seville, , Spain

Adult and Pediatrics Endocrinology and Diabetology, Hospital Miguel Servet

Zaragoza, , Spain

Barn- och Ungdomskliniken, Universitetssjukhuset

Linköping, , Sweden

Endokrinmedicinska kliniken. Universitetssjukhuset

Linköping, , Sweden

Barn-och Ungdomsmedicinmottagningen and Endokrinmottagningen, Skånes Universitetssjukhus

Malmo, , Sweden

Barn- och ungdomskliniken, Uddevalla Sjukhus

Uddevalla, , Sweden

Diabetesmottagningen, Uddevalla Sjukhus

Uddevalla, , Sweden

Barnmottagningen, Norrlands Universitetssjukhus

Umeå, , Sweden

Countries

Czechia; Netherlands; Spain; Sweden

References

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.

Reference Type: BACKGROUND

PMID: 28199812 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28745988 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36817467 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35665810 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34021020 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.diagnode-2.com

Information regarding the clinical trial

Other Identifiers

2017-001861-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

DIAGNODE-2 (D/P2/17/6)

Identifier Type: -

Identifier Source: org_study_id