DIAGNODE-3 study for recently diagnosed type I diabetes

(DIAGNODE-3 Trial)

Recruiting at 111 trial locations

Overseen By Chief Operating Officer

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Diamyd Medical AB

Must be taking: Insulin

Must not be taking: Anti-diabetics, Immunosuppressants

Disqualifiers: Pancreatic disorders, Hepatic disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 5

Duration: 3 months

330 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests if using Diamyd and Vitamin D can help young people and adults with Type 1 Diabetes. The goal is to help their bodies keep making insulin for longer. High dose vitamin D and omega 3 have shown promise in prolonging remission in Type 1 Diabetes.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop taking any oral or non-insulin injectable anti-diabetic medications within 3 months prior to joining. You must also stop taking any Vitamin D supplements and switch to the study-provided Vitamin D. Other medications are not specifically mentioned, so consult with the trial team for guidance.

What safety data is available for the treatment in the DIAGNODE-3 study for type 1 diabetes?

The treatment, known as GAD-alum or Diamyd, has been evaluated in several studies. These studies, including phase II and III trials, have shown that the treatment is safe and well-tolerated in children, adolescents, and adults with recent-onset type 1 diabetes or latent autoimmune diabetes. The safety data from these trials indicate that the treatment does not cause significant adverse effects and is considered safe for use in clinical settings. ^{1 2 3 4 5}

Is the drug Diamyd a promising treatment for recently diagnosed type 1 diabetes?

Yes, Diamyd, which is a drug made from a protein called GAD65, shows promise in treating recently diagnosed type 1 diabetes. Studies suggest it can help preserve the body's ability to produce insulin, which is important for managing diabetes. ^{1 2 3 4 5}

What data supports the idea that DIAGNODE-3 study for recently diagnosed type I diabetes is an effective treatment?

The available research shows that the treatment, which involves using a special protein called GAD-alum, helps preserve the body's ability to produce insulin in children and adolescents with type 1 diabetes. Studies have shown that after receiving the treatment, patients maintained some insulin production for up to 30 months. This suggests that the treatment can slow down the progression of the disease by protecting the insulin-producing cells in the pancreas. Additionally, the treatment was found to be safe and well-tolerated in clinical trials. ^{1 2 3 5 6}

Who Is on the Research Team?

Johnny Ludvigsson, Professor

Principal Investigator

Crown Princess Victoria Children´s Hospital and Linköping University

Are You a Good Fit for This Trial?

We are recruiting adolescents and adults recently diagnosed with type I diabetes who carry the the genetic human leukocyte antigen (HLA) Dr3-DQ2 haplotype. A haplotype is a group of genes, often inherited together and part of your genetic makeup, or DNA. Participants will be initially screened to see if they carry this HLA genotype and thereby qualify for the study.

Inclusion Criteria

I was diagnosed with Type 1 Diabetes less than 6 months ago.

My insulin dose has been stable for the last month.

Have you been diagnosed with type 1 diabetes within the last 6 months?

Exclusion Criteria

I haven't had any vaccines, including flu and COVID-19, in the last 4 weeks and won't have any for 4 weeks after starting the study drug.

I haven't taken any diabetes pills or non-insulin injections in the last 3 months.

I do not have any severe inherited blood disorders, except for sickle cell trait or thalassemia minor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants receive three intralymphatic injections of Diamyd or placebo at one-month intervals, along with oral Vitamin D supplementation

3 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

21 months

Regular visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Colecalciferol 2000 IU
• Placebo for recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel®
• Recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel®

Trial Overview The active ingredient in Diamyd is the human protein glutamic acid decarboxylase (GAD). Treatment with Diamyd is thought to intervene in the autoimmune attack and thereby preserve the body's ability to produce insulin.

How Is the Trial Designed?

Group I: Diamyd Experimental Treatment 2 Interventions

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

Group II: Placebo Placebo Group 2 Interventions

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

Placebo for recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel® is already approved in United States, European Union for the following indications:

Approved in United States as Diamyd for:

• Type 1 Diabetes (Stage 3) in patients with HLA DR3-DQ2 genotype

Approved in European Union as Diamyd for:

• Type 1 Diabetes in patients with HLA DR3-DQ2 genotype

Who Is Running the Clinical Trial?

Diamyd Medical AB

Lead Sponsor

Trials

9

Recruited

600+

Published Research Related to This Trial

GAD-alum is a vaccine designed to induce immune tolerance to GAD65, a protein targeted by the immune system in Type 1 diabetes, potentially preventing further damage to insulin-producing β-cells.

Clinical trials are currently assessing the safety and efficacy of GAD-alum immunotherapy in patients with Type 1 diabetes and other autoimmune diabetes forms, indicating a promising approach to managing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GAD-alum immunotherapy in Type 1 diabetes mellitus. Morales, AE., Thrailkill, KM.[2013]

In a 4-year study involving 70 children and adolescents with recent-onset type 1 diabetes, GAD-alum treatment showed a significant preservation of insulin secretion (C-peptide levels) compared to placebo, especially in patients diagnosed within 6 months.

The treatment was found to be safe, with no serious adverse events reported, indicating that GAD-alum could be a promising option for managing type 1 diabetes in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. Ludvigsson, J., Hjorth, M., Chéramy, M., et al.[2021]

In a combined analysis of two studies involving 70 children and adolescents, treatment with two doses of GAD-alum showed no adverse events and effectively preserved insulin secretion over 30 months.

Patients receiving GAD-alum had significantly less decline in stimulated C-peptide levels compared to those receiving a placebo, indicating better maintenance of insulin production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GAD-treatment of children and adolescents with recent-onset type 1 diabetes preserves residual insulin secretion after 30 months. Ludvigsson, J., Chéramy, M., Axelsson, S., et al.[2022]

Diamyd, an alum formulation of a recombinant human protein, has shown safety and tolerability in Phase II clinical trials for adults with type 1 diabetes (T1DM) and latent autoimmune diabetes (LADA).

The drug is currently advancing through Phase II/III and III clinical trials, indicating ongoing research into its efficacy for preventing and treating T1DM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diamyd, an alum-formulated recombinant human GAD65 for the prevention of autoimmune diabetes. Hinke, SA.[2016]

In a study involving 70 children with recent-onset type 1 diabetes, treatment with GAD-alum led to an early enhancement of T-helper 2 immune responses, specifically increasing levels of IL-5 and IL-13 just one month after the first injection.

The immunomodulatory effects of GAD-alum continued to evolve over time, with a broader range of cytokines being produced at 3 and 9 months, indicating a sustained immune response that may help preserve insulin secretion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65). Axelsson, S., Hjorth, M., Akerman, L., et al.[2016]

In a study involving 334 patients aged 10 to 20 with recent-onset type 1 diabetes, treatment with GAD-alum did not significantly preserve beta-cell function compared to placebo, as measured by stimulated C-peptide levels over 15 months.

GAD-alum treatment also showed no impact on secondary outcomes such as insulin dosage, glycated hemoglobin levels, or rates of hypoglycemia, indicating that it may not be an effective intervention for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. Ludvigsson, J., Krisky, D., Casas, R., et al.[2012]

Citations

1. England pubmed.ncbi.nlm.nih.gov

GAD-alum immunotherapy in Type 1 diabetes mellitus. [2013]

2. Germany pubmed.ncbi.nlm.nih.gov

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial. [2021]

3. England pubmed.ncbi.nlm.nih.gov

GAD-treatment of children and adolescents with recent-onset type 1 diabetes preserves residual insulin secretion after 30 months. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Diamyd, an alum-formulated recombinant human GAD65 for the prevention of autoimmune diabetes. [2016]

5. England pubmed.ncbi.nlm.nih.gov

Early induction of GAD(65)-reactive Th2 response in type 1 diabetic children treated with alum-formulated GAD(65). [2016]

6. United States pubmed.ncbi.nlm.nih.gov

GAD65 antigen therapy in recently diagnosed type 1 diabetes mellitus. [2012]