Diamyd Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes
Condition: Diabetes Mellitus, Type 1; Diabetes Mellitus; Autoimmune Diseases; Metabolic Disease; Glucose Metabolism Disorders; Immune System Diseases; Endocrine System Diseases; Juvenile Diabetes; Insulin Dependent Diabetes; Autoimmune Diabetes; Vitamin D; Physiological Effects of Drugs
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases
Intervention: Diamyd; Vitamin D; Placebo for Diamyd; Placebo for Vitamin D
Intervention description: Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD65); Oil suspension of Vitamin D; Alhydrogel® only; Placebo oil suspension for Vitamin D
Intervention MeSH terms: Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The study is a 2-arm, randomized, double-blind, placebo-controlled, multicenter, clinical trial.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 109.0
Sex: All
Minimum age: 12 Years
Maximum age: 24 Years
Healthy volunteers: No
Keywords: Diamyd; Diabetes; Juvenile Diabetes; Diabetes Type 1; Type 1 Diabetes; Autoimmune Diabetes; Insulin Dependent Diabetes; Type 1 Diabetes Mellitus; rhGAD65; GAD65; Diabetes Mellitus; Diabetes Mellitus Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Vitamin D; Vitamins; Micronutrients; Cholecalciferol; Ergocalciferols

Summary:

      The objective of DIAGNODE-2 is to evaluate the efficacy of Diamyd compared to Placebo, upon
      administration directly into a lymph node in combination with an oral vitamin D/Placebo
      regimen, in terms of preserving endogenous insulin secretion as measured by C-peptide.
    

Eligibility criteria:

        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. Type 1 Diabetes (T1D) according to the Amercian Diabetes Association (ADA)
             classification diagnosed ≤6 months at the time of screening

          3. Age: ≥12 and <25 years old

          4. Fasting C-peptide ≥0.12 nmol/L (0.36 ng/ml) on at least one occasion (maximum 2 tests
             on different days within a period of 2 weeks)

          5. Positive for Glutamic Acid Decarboxylase isoform 65 (GAD65A) but < 50 000 IU/ml

          6. Females must agree to avoid pregnancy and have a negative urine pregnancy test.
             Patients of childbearing potential must agree to use adequate contraception, until one
             (1) year after the last administration of Diamyd. Adequate contraception is as
             follows:

        For females of childbearing potential:

          1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or
             implanted hormonal contraceptives

          2. combined (estrogen and progestogen containing)

          3. oral, intravaginal or transdermal progesterone hormonal contraception associated with
             inhibition of ovulation

          4. intrauterine device

          5. intrauterine hormone-releasing system (for example, progestin-releasing coil)

          6. bilateral tubal occlusion

          7. vasectomized male (with appropriate post vasectomy documentation of the absence of
             sperm in the ejaculate)

          8. male partner using condom

          9. abstinence from heterosexual intercourse

        For males of childbearing potential:

          1. condom (male)

          2. abstinence from heterosexual intercourse

        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. A history of anemia or significantly abnormal hematology results at screening

          5. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features
             of continuous motor unit activity in proximal muscles

          6. Clinically significant history of acute reaction to vaccines or other drugs in the
             past

          7. Treatment with any vaccine, including influenza vaccine, within 4 months prior to
             planned first study drug dose or planned treatment with any vaccine up to 4 months
             after the last injection with study drug.

          8. Participation in other clinical trials with a new chemical entity within the previous
             3 months

          9. Inability or unwillingness to comply with the provisions of this protocol

         10. A history of alcohol or drug abuse

         11. A significant illness other than diabetes within 2 weeks prior to first dosing

         12. Known HIV or hepatitis

         13. 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/placebo treatment)

         14. 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

         15. Deemed by the investigator not being able to follow instructions and/or follow the
             study protocol