Study to Evaluate the Safety and Feasibility of Diamyd® in Individuals At Risk for Type 1 Diabetes

A 2-arm randomized Phase II Open Label Study to evaluate the safety and feasibility of intralymphatic administration of Diamyd® (Diamyd) in individuals at risk of Type 1 diabetes carrying the HLA DR3-DQ2 haplotype.

The trial is a 2-arm, randomized, open label clinical trial in individuals aged 8 - \<18 years with HLA DR3-DQ2 and multiple islet autoantibodies (Stage 1 or Stage 2) at increased risk for T1D. At baseline eligible individuals at risk of T1D will be randomized 1:1 into 2 or 3 injections of Diamyd® administered into an inguinal lymph node. Subjects will be followed for a total of 12 months post-enrollment.

Eligibility Criteria:
Inclusion Criteria:

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

Exclusion Criteria:

1. Diagnosis of T1D (stage 3 T1D, according to the American Diabetes Association \[ADA\] classification).
2. 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.
3. Treatment with any anti-diabetic medication, including the use of external insulin.
4. Participation in any other clinical trial testing pharmaceutical treatments.
5. 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.
6. History of hyperparathyroidism, hypercalcemia and/or nephrolithiasis, unless appropriately treated, or any other contraindication to use of Vitamin D.
7. History of epilepsy, serious head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
8. Any clinically significant history of an acute reaction to a vaccine or its constituents (e.g., Alhydrogel) or lidocaine (local anesthetic)
9. Any acute or chronic skin infection or condition that would preclude intralymphatic injection.
10. 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.
11. Ongoing diagnosed post-COVID19 syndrome.
12. 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.
13. 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.
14. Any clinically significant abnormal findings detected during Screening that might jeopardize the individual's safety or ability to complete the trial.
15. 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).
16. 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)

1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
2. intrauterine device
3. intrauterine system (for example, progestin-releasing coil)
4. refraining from heterosexual intercourse if that is the preferred and usual lifestyle of the subject.

For sexually active males

1. condom
2. Abstinence from heterosexual intercourse if that is the preferred and usual lifestyle of the subject.