DIAGNODE-3 study for recently diagnosed type I diabetes

(DIAGNODE-3 Trial)

Recruiting at 118 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 investigates a treatment for individuals recently diagnosed with type 1 diabetes. The researchers aim to determine if a series of injections, combined with Vitamin D, can help maintain the body's natural insulin production and manage blood sugar levels. Participants will receive either the study drug (recombinant human glutamic acid decarboxylase, rhGAD65, formulated in Alhydrogel®) or a placebo, both combined with Vitamin D. Suitable candidates include those diagnosed with type 1 diabetes within the last six months, who have stable insulin requirements, and have tested positive for certain genetic markers. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the active ingredient in Diamyd, recombinant human glutamic acid decarboxylase (rhGAD65), has been safe in previous studies. The treatment is generally well-tolerated when combined with alum, which enhances the body's immune response.

In earlier studies, participants received several injections of this treatment without major safety issues. The treatment did not harm the beta cells, which are crucial for insulin production. Maintaining beta cell function is a key goal in treating type 1 diabetes.

For those considering joining a clinical trial for this treatment, existing evidence suggests it has been safe in past research. However, discussing any concerns with a healthcare provider before making a decision is always wise. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for type 1 diabetes?

Unlike the standard treatments for type 1 diabetes, which typically involve insulin therapy to manage blood sugar levels, Diamyd targets the immune system directly. This treatment uses recombinant human glutamic acid decarboxylase (rhGAD65) formulated in Alhydrogel® to potentially preserve the insulin-producing cells in the pancreas. Researchers are excited about Diamyd because it is administered through intralymphatic injections, which might enhance the immune system's response more effectively than traditional methods. Additionally, combining this with oral vitamin D could further support the immune-modulating effects, offering a novel approach to managing type 1 diabetes from its roots rather than just its symptoms.

What evidence suggests that this trial's treatments could be effective for type 1 diabetes?

Research has shown that a substance called rhGAD65 might help people with type 1 diabetes continue producing insulin. One study found that rhGAD65 works with the immune system to protect insulin-producing cells in the pancreas. Another study discovered that combining rhGAD65 with vitamin D improved insulin production and helped control blood sugar levels in some patients. In this trial, participants in the Diamyd arm will receive rhGAD65 with vitamin D, while those in the Placebo arm will receive a placebo with vitamin D. These findings suggest that rhGAD65, especially when combined with vitamin D, could effectively manage type 1 diabetes by supporting the body's insulin production. ^{2 6 7 8 9}

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

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 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]

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]

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]

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]

Citations

1. repository.niddk.nih.gov repository.niddk.nih.gov/media/studies/tn08-gad-new-onset/Protocol.pdf

Effects of Recombinant Human Glutamic Acid Decarboxylase ... Objective. It is hypothesized that multiple injections with 20µg GAD-alum preserves endogenous insulin production in type 1-diabetes patients 3-45 years of age, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00529399?tab=results

Study Results | Effects of Recombinant Human Glutamic ... A general description of the clinical trial arm. It identifies the role of the intervention that participants receive. Types of arms include experimental arm, ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa0804328

GAD Treatment and Insulin Secretion in Recent-Onset ... The 65-kD isoform of glutamic acid decarboxylase (GAD) is a major autoantigen in patients with type 1 diabetes mellitus. This trial assessed the ability of ...

4. diabetesjournals.org diabetesjournals.org/care/article/44/7/1604/138800/Intralymphatic-Glutamic-Acid-Decarboxylase-With

Intralymphatic Glutamic Acid Decarboxylase With Vitamin D ... This strategy has been successful in allergy immunotherapy (18) and was tested in T1D in a pilot trial with GAD-alum injected into an inguinal ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2405844021027985

The early detection of type 1 diabetes mellitus and latent ... We have developed a rapid test for anti-GAD65 autoantibodies in this assay based on the reverse-flow immunochromatography method.

6. diamyd.com diamyd.com/docs/prodfiles/10-65702-01_rhGAD65_Product_Data_Sheet.pdf

product data sheet 10-65702-01 rhgad65 Protective equipment: Wear suitable protective clothing, such as a lab coat, chemical resistant gloves and chemical safety goggles. Respiratory protection and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00529399

Study Details | NCT00529399 | Effects of Recombinant ... The purpose of this study is to determine whether treatment with multiple injections of GAD-Alum will preserve the body's own (endogenous) insulin production in ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1056872705000036

Original article Clinical evidence for the safety of GAD65 ... The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function.

9. repository.niddk.nih.gov repository.niddk.nih.gov/study/78

TrialNet 08: Effects of Recombinant Human Glutamic Acid ... The primary objective was to assess whether immunization with glutamic acid decarboxylase (GAD) formulated with aluminum hydroxide (GAD-alum) would preserve ...