E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | LLT |
E.1.2 | Classification code | 10045228 |
E.1.2 | Term | Type I diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 feasibility and safety of administering an additional intralymphatic booster dose of Diamyd.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to evaluate the effect of the treatment with an additional booster dose of Diamyd on the preservation of endogenous insulin secretion, diabetes status and the immune system. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent given by patients and/or patient’s parent(s) or legal acceptable representative(s) (guardian(s)) according to national regulations 2. T1D according to the ADA classification 3. Carry HLA DR3-DQ2 haplotype 4. Prior participation in either the DIAGNODE-1 or the DIAGNODE-2, having received four or three intralymphatic injections of Diamyd, respectively. 5. Females must agree to avoid pregnancy and have a negative urine pregnancy test. Patients of childbearing potential must agree to use adequate contraception, until 90 days after the administration of Diamyd. Adequate contraception is as follows: For females of childbearing potential: a. oral (except low‐dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives b. combined (estrogen and progestogen containing) c. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation d. intrauterine device e. intrauterine hormone-releasing system (for example, progestin‐releasing coil) f. bilateral tubal occlusion g. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate) h. male partner using condom i. abstinence from heterosexual intercourse For males of childbearing potential: a. condom (male) b. abstinence from heterosexual intercourse |
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E.4 | Principal exclusion criteria |
1. Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted) 2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted) 3. Treatment with any oral or injected anti-diabetic medications other than insulin 4. Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the supplementation period 5. A history of anemia or significantly abnormal hematology results at screening 6. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles 7. Clinically significant history of acute reaction to vaccines or other drugs in the past, including Diamyd 8. Treatment with any vaccine, including influenza or Covid19 vaccine, within 1 month prior to planned study drug dose administration or planned treatment with any vaccine up to 1 month after the injection with study drug 9. Participation in clinical trials (other than DIAGNODE-1 and DIAGNODE-2) with a new chemical entity within the previous 3 months 10. Inability or unwillingness to comply with the provisions of this protocol 11. A history of alcohol or drug abuse 12. A significant illness other than diabetes within 2 weeks prior to first dosing s 13. Ongoing diagnosed or suspected post-Covid19 syndrome 14. Known HIV or hepatitis 15. Females who are lactating or pregnant (the possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior to the Diamyd treatment) 16. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study 17. Deemed by the investigator not being able to follow instructions and/or follow the study protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in this study is to evaluate the feasibility and safety of an additional booster dose of Diamyd, administered into an inguinal lymph node. The variables to evaluate safety are: • Injection site reactions • Occurrence of AEs and SAEs • Laboratory measurements (hematology and clinical chemistry) • Urine analysis (albumin, creatinine) • Physical examinations, including neurological and Vital Signs assessments |
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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) |
The secondary endpoints to evaluate diabetic status are: • Change in C-peptide (Area Under the Curve [AUC]mean 0-120 min-) during a Mixed Meal Tolerance Test (MMTT) between baseline to 12 months. • Change in HbA1c between baseline and 12 months. • Change in daily exogenous insulin consumption between baseline and 12 months. • Change in insulin-dose-adjusted HbA1c (IDAA1c) between baseline and 12 months. • Change in time in glycemic target range 3.9 to 10 mmol/L (70 to 180 mg/dL) [evaluated from CGM data] between baseline and 12 months. • Change in time in hyperglycemic range > 10 mmol/L (> 180 mg/dL) [evaluated from CGM data] between baseline and 12 months.
Exploratory endpoints • Change in maximum C-peptide during MMTT between baseline and 12 months. • C-peptide measured at 30, 60, 90, and 120 minutes during MMTT between baseline and 12 months. • Change in Fasting C-peptide between baseline and 12 months. • Number of self-reported episodes of severe hypoglycemia (Severe hypoglycemia defined as needing help from others and/or seizures and/or unconscious) and DKA. • Number of self-reported episodes of diabetic ketoacidosis • Change in serum GAD65 antibody titers. • Change concentrations of serum GAD65 autoantibody subclasses. • Change in secretion of relevant cytokines such as interleukin (IL)-10, IL-13 and, interferon (IFN)γ, by peripheral blood mononuclear cells (PBMCs) upon stimulation with GAD65. • Change in proliferation of PBMCs upon stimulation with GAD65. • Further exploratory immunological characterization. |
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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 | No |
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 | No |
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 | No |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
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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Last visit of last subject |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |