Evaluation of Intralymphatic Administration of Recombinant Human Glutamate Decarboxylase 2 in HLA DR3-DQ2 Positive Individuals at Risk for Type 1 Diabetes

Trial ID: 2024-513350-30-00
Protocol: D/P2/22/8
Sponsor: Diamyd Medical AB

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Diseases & Conditions

Type 1 diabetes mellitus

Objectives

The primary objective of this study is to evaluate the **feasibility** and **safety** of administering two and three intralymphatic injections of Diamyd, spaced one month apart, in individuals aged 8 to less than 18 years who possess the HLA haplotype DR3-DQ2 and multiple islet autoantibodies, placing them at increased risk for **Type 1 diabetes mellitus**. This evaluation is clinically relevant as it aims to determine the potential of Diamyd to safely delay or prevent the onset of Type 1 diabetes in a high-risk population, which could significantly impact disease management and patient outcomes.

The secondary objectives are to assess the effect of Diamyd treatment on the individuals' immune system and metabolic status, as well as the progression from stage 1 to stage 2, or from stage 2 to stage 3 of Type 1 diabetes. These evaluations are crucial for understanding the broader implications of Diamyd treatment on disease progression and patient health.

Participants

The clinical trial involves a study population of **children and adolescents** aged 8 to less than 18 years, both male and female, who are at increased risk for **Type 1 diabetes mellitus**. Participants possess the HLA haplotype DR3-DQ2 and are seropositive for multiple islet autoantibodies, including GADA and at least one additional T1D-associated autoantibody such as IA-2A, ZnT8A, or IAA. The trial focuses on a vulnerable population, requiring written informed consent or assent from the participants and their parents or caretakers. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria emphasize the presence of specific genetic and immunological markers, ensuring the inclusion of individuals at a particular stage of risk for developing Type 1 diabetes.

Plans and Procedures

The clinical trial is designed to evaluate the **feasibility** and **safety** of intralymphatic administration of Diamyd in individuals at risk for **Type 1 diabetes mellitus**. This is a Phase II open-label study involving participants aged 8 to less than 18 years who possess the HLA DR3-DQ2 haplotype and are seropositive for multiple islet autoantibodies. The trial will assess the effects of two or three injections of Diamyd, administered one month apart, into an inguinal lymph node. The study is expected to commence recruitment on October 4, 2024, and conclude by December 31, 2026.

The trial follows a structured sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the principal inclusion criteria, which include obtaining written informed consent from participants and their guardians. Participants will then undergo a series of follow-up visits corresponding to each injection, spaced one month apart, to monitor safety and feasibility outcomes. The end-of-study visit will occur after the final injection to assess the primary endpoint, which focuses on the feasibility and safety of the treatment regimen.

Participant involvement is expected to last for a maximum of two months, aligning with the treatment period of two to three injections. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events that compromise participant safety, or any protocol deviations that affect the integrity of the trial. The study is not classified as a low-intervention trial, and it does not involve a pediatric formulation. The trial is conducted under the sponsorship of Diamyd Medical AB, with the investigational product being a suspension for injection containing the active substance **glutamate decarboxylase 2, human, recombinant**. The trial does not include any secondary endpoints or additional medicinal products.

Treatment

The clinical trial involves the administration of the experimental medication **Diamyd**, which is a **suspension for injection**. The active substance in Diamyd is **glutamate decarboxylase 2, human, recombinant**, a protein of non-human origin. The pharmaceutical form of Diamyd is specifically designed for **intralymphatic use**. The dosing regimen consists of a maximum daily dose of 4 µg micrograms, with a total maximum dose of 12 µg micrograms over the treatment period. The treatment is administered over a period of 2 months, with injections given one month apart. The study aims to evaluate the safety and feasibility of this administration method in individuals at risk for Type 1 diabetes.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are utilized in this study. The focus is solely on the administration of Diamyd to assess its effects. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol. The trial is conducted under the sponsorship of Diamyd Medical AB, and the product is not classified as an orphan drug. The formulation is not specifically pediatric, although the study includes participants aged 8 to less than 18 years.

Efficacy

The clinical trial aims to assess the **efficacy** of Diamyd, a suspension for injection containing the active substance glutamate decarboxylase 2, human, recombinant. The primary endpoint focuses on evaluating the feasibility and safety of administering two or three intralymphatic injections of Diamyd into an inguinal lymph node. This study targets individuals aged 8 to less than 18 years who possess the HLA DR3-DQ2 haplotype and are seropositive for multiple islet autoantibodies, indicating an increased risk for Type 1 diabetes. The trial is designed as a Phase II open-label study, with the primary objective of determining the safety and feasibility of the treatment regimen. The trial is scheduled to commence recruitment on October 4, 2024, and is expected to conclude by December 31, 2026.

Inclusion and Exclusion Criteria

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Inclusion Criteria

Written informed consent/assent from the individual and the individual's parents or caretaker(s)
Males and females aged ≥8 and <18 years old at the time of Screening.
Possess the HLA DR3-DQ2 haplotype.
Seropositive for GADA and at least one additional T1D-associated autoantibody (IA-2A, ZnT8A or IAA).

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Exclusion Criteria

Diagnosis of T1D (stage 3 T1D, according to the American Diabetes Association [ADA] classification).
Fasting glucose > 7 mmol/L (126 mg/dl), 2-hour-OGTT plasma glucose > 11.1 mmol/L (200 mg/dL) or HbA1c > 6.5% (48 mmol/mol) at the screening Visit.
Treatment with any anti-diabetic medication, including the use of external insulin.
Participation in any other clinical trial testing pharmaceutical treatments.
Recent (past 12 months) or current treatment with immunosuppressant therapy, including chronic use of glucocorticoid therapy. Inhaled, topical, and intranasal steroid use is acceptable. Short courses (e.g., ≤5 days) of oral or intra-articular injections of steroids will be permitted on trial.
History of hyperparathyroidism, hypercalcemia and/or nephrolithiasis, unless appropriately treated, or any other contraindication to use of Vitamin D.
History of epilepsy, serious head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles.
Any clinically significant history of an acute reaction to a vaccine or its constituents (e.g., Alhydrogel) or lidocaine (local anesthetic)
Any acute or chronic skin infection or condition that would preclude intralymphatic injection.
Treatment with any (live or inactive) vaccine, including influenza vaccine and Coronavirus Disease 2019 (COVID-19) vaccine, within 4 weeks prior to planned first dose of study drug; or planned treatment with any vaccine up to 4 weeks after the last injection with study drug.
Ongoing diagnosed post-COVID19 syndrome.
Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. Individuals with previous hepatitis C infection that is now cured may be eligible.
Any clinically significant concomitant medical condition, including but not limited to other autoimmune diseases, cardiovascular, gastrointestinal, hematological, immune, renal including a history of renal transplantation or neurological that in the opinion of the investigator would interfere with trial participation or procedures. Celiac disease with adequate diet as well as stable autoimmune thyroiditis will be permitted.
Any clinically significant abnormal findings detected during Screening that might jeopardize the individual's safety or ability to complete the trial.
Females who are lactating or pregnant (for females who have started menstruating the possibility of pregnancy must be excluded by urine βHCG onsite prior to the study drug administration).
Males or females not willing to use adequate contraception, if sexually active, until 90 days after the last Diamyd administration. Adequate contraception is as follows: For females of childbearing potential (FOCBP) a. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives b. intrauterine device c. intrauterine system (for example, progestin-releasing coil) d. refraining from heterosexual intercourse if that is the preferred and usual lifestyle of the subject. For sexually active males a. condom b. Abstinence from heterosexual intercourse if that is the preferred and usual lifestyle of the subject. c. Vasectomy