HLA DR3-DQ2 Haplotype Type 1 diabetes
Conditions
Interventions
At Visit 2, patients will be randomized 2:1 to one of the following two
treatment groups:
Treatment Group 1: 3 intralymphatic injections of 4 µg (0.1 mL) of Diamyd
administered on Days 0, 30 and 60
Sponsors
ICON Clinical Research
Eligibility
Age
12 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Must be capable of providing written, signed, and dated informed consent; and for patients who are minors, age-appropriate assent (performed according to local regulations) and parent/caregiver consent. 2. Males and females aged >=12 and =0.12 nmol/L (>=0.36 ng/mL) on at least one occasion (maximum two tests on different days during the Screening period). 6. Possess detectable circulating GAD65 antibodies (lowest level of detection defined by the method used by the central laboratory). 7. Possess HbA1c levels between 35 to 80 mmol/mol (5.4 to 9.5%) on at least one occasion prior to randomization (maximum one additional test within one month from V1B). 8. Be on a stable insulin dose or insulin dosing regimen for one month prior to inclusion with limited fluctuation of daily insulin requirement based on investigator*s assessment. For example, if the average insulin dose/kg/24h over a 7-day period compared to the previous 7day period does not vary more than approximately 15% and/or if the daily insulin dose does not vary more than 0.1 U/kg/24h, the dose can be considered stable. Individuals that are diagnosed with T1D according to the ADA classification but are not taking insulin are eligible to participate. 9. (i). Females of childbearing potential (FOCBP) must agree to avoid pregnancy and have a negative pregnancy test performed at the required study visits. FOCBP must agree to use highly effective contraception, during treatment and, until 90 days after the last administration of study medication. Birth control methods, which may be considered as highly effective (e.g., a failure rate of less than 1% per year when used consistently and correctly) include: • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: o Oral. o Intravaginal. o Transdermal. • Progestogen-only hormonal contraception associated with inhibition of ovulation: o Oral. o Injectable. o Implantable. • Intrauterine device. • Intrauterine hormone-releasing system. • Bilateral tubal occlusion. • Vasectomized partner (vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner of the FOCBP trial patient and that the vasectomized partner has received medical assessment of the surgical success). • Sexual abstinence (sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient). 9. (ii). Male patients must agree to remain abstinent from heterosexual sex during treatment and for 90 days after treatment or, if sexually active, to use two effective methods of birth control (e.g., male uses a condom and female uses contraception) during and for 90 days after treatment. Acce
Exclusion criteria
Exclusion criteria: 1. Participation in any other trial aimed to influence beta cell function from time of diagnosis of T1D. 2. Treatment with any oral or non-insulin injectable anti-diabetic medication within 3 months prior to Randomization. 3. History of maturity-onset diabetes of the young (MODY). 4. Pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased beta cell capacity. 5. Occurrence of DKA or severe hypoglycemia requiring hospitalization in the period of 90 days prior to Randomization. 6. Signs or symptoms suggesting very poorly controlled diabetes e.g., ongoing weight loss, polyuria or polydipsia. 7. Hematologic condition that would make HbA1c uninterpretable including: a) Hemoglobinopathy, with the exception of sickle cell trait or thalassemia minor; or chronic or recurrent hemolysis. b) Donation of blood or blood products to a blood bank, blood transfusion or participation in a clinical study requiring withdrawal of >400 mL of blood during the 8 weeks prior to the Screening (V1B) visit. c) Significant iron deficiency anemia. d) Heart malformations or vaso-occlusive crisis (VOC) leading to increased turnover of erythrocytes. 8. Treatment with marketed or over-the-counter Vitamin D at the time of Screening (V1C) and unwilling to abstain from such medication during the 120 days when the patient will be supplemented with the study-provided Vitamin D. A patient currently taking Vitamin D at the time of Screening (V1C) must be willing to switch to the study-provided Vitamin D treatment and to administer it per the study requirements. 9. Any clinically significant history of an acute reaction to a vaccine or its constituents (e.g., Alhydrogel). 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 study dose of study drug; or planned treatment with any vaccine up to 4 weeks after the last injection with study drug. 11. Any acute or chronic skin infection or condition that would preclude intralymphatic injection. 12. 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. 13. Continuous/chronic treatment with prescribed or over-the-counter anti-inflammatory therapies. Short-term use (e.g., <7 days) is permissible, for example to treat a headache or in connection with a fever. 14. Known or suspected acute infection, including COVID-19 or influenza, at the time of Randomization or within 4 weeks prior to Randomization. 15. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles. 16. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection. Patients with previous hepatitis C infection that is now cured may be eligible. 17. 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, neurological (including Batten disea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treatment: Intralymphatic injections of 4 µg Diamyd or placebo. Target population: Study participants diagnosed with T1D who carry the HLA DR3-DQ2 haplotype and have antibodies against GAD65. Variable: Change from baseline to Month 24 in C peptide area under the curve (AUC)mean 0-120 min during a 2-hour mixed meal tolerance test (MMTT) Intercurrent event strategy: 1. Study drug discontinuation due to any cause, patient does not withdraw consent: treatment policy strategy. 2. Study drug discontinuation due to any cause, patient withdraws consent: hypothetical strategy. 3. Study drug non-adherence (missing doses) or drug administration error: treatment policy strategy. 4. Prohibited medications and substances, including additional medication (oral or non-insulin injectable therapies) for glycemic control (Sponsor*s Medical Experts will take decision if patient can continue or should be discontinued): hypothetical (if patient is discontinued), or treatment policy (if patient continues in the study) strategy. Population level summary: The geometric mean ratio (Diamyd/placebo) of the change from baseline in C-peptide AUCmean 0-120 min. | — |
Secondary
| Measure | Time frame |
|---|---|
| Treatment: as above. Target population: as above. Variable: Change from baseline to Month 24 in hemoglobin A1c (HbA1c). Intercurrent event strategy: as above. Population level summary: Mean difference in change from baseline. | — |
Countries
Netherlands
Outcome results
None listed