E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage 1 or stage 2 pre-type1 diabetes (seropositive for two or more T1D–associated autoantibodies) |
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E.1.1.1 | Medical condition in easily understood language |
Prediabetes (the autoimmune process leading to type 1 diabetes) |
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E.1.1.2 | Therapeutic area | Body processes [G] - Metabolic Phenomena [G03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to evaluate the feasibility and safety of two and three intralymphatic injections of Diamyd (one month apart) in individuals aged 8 - <18 years with Human Leukocyte Antigen (HLA) haplotype DR3-DQ2 and multiple islet autoantibodies (Stage 1 or Stage 2) at increased risk for Type 1 Diabetes (T1D). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the effect of Diamyd treatment on the individuals’ immune system and metabolic status as well as progression from Stage 1 to Stage 2 or Stage 3 T1D. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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). |
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E.4 | Principal 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) 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary endpoint • Variables that indicate safety and feasibility of treatment: - Occurrence of AEs (including Injection site reactions) and SAEs - Physical examinations, including neurological assessments - Laboratory measurements, including hematology, clinical chemistry, metabolic status parameters (fasting C-peptide, HbA1c, fasting glucose) and urine analysis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints • Number of individuals progressing from stage 1 to stage 2 and from stage 2 to stage 3. • Time to T1D diagnosis. • Time from stage 1 to stage 2. and time from stage 2 to stage 3. • Change in C-peptide /insulin /glucose (Area Under the Curve [AUC]mean 0-120 min) during a 2-hour Oral Glucose Tolerance Test (OGTT) from screening to 6, 12 months. • Change in Hemoglobin A1c (HbA1c) from baseline to 6, 12 months. • Change in time in glycemic target range 3.9 to 10 mmol/L (70 to 180 mg/dL) and 3.9 to 7.8 mmol/L (70 to 140 mg/dL) evaluated from continuous glucose monitoring (CGM) data from screening to 6, 12 months. • Change in time in range > 13.9 mmol/L (> 250 mg/dL) evaluated from CGM data from screening to 6, 12 months. • Change in time in range > 10 mmol/L (> 180 mg/dL) evaluated from CGM data from screening to 6, 12 months. • Change in time in range > 7.8 mmol/L (> 140 mg/dL) evaluated from CGM data from screening to 6, 12 months. • Change in glycemic variation (Coefficient of variation [CV], SD) evaluated from CGM data from screening to 6, 12 months. • Variables that indicate effects on the immune system such as the concentration of serum autoantibodies. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |