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GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT03345004
Recruitment Status : Completed
First Posted : November 17, 2017
Last Update Posted : September 17, 2021
Sponsor:
Information provided by (Responsible Party):
Diamyd Medical AB

Brief 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.

Condition or disease Intervention/treatment Phase
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 Biological: GAD-alum Dietary Supplement: Vitamin D Biological: Placebo for Diamyd (GAD-alum) Dietary Supplement: Placebo for Vitamin D Phase 2

Detailed Description:
The study is a 2-arm, randomized, double-blind, placebo-controlled, multicenter, clinical trial. Eligible patients will receive injections of Diamyd/placebo into an inguinal lymph gland at three occasions, with one month intervals in combination with an oral vitamin D/placebo regimen (starting 1 month ahead of injections) during 4 months. All patients will continue to receive intensive insulin treatment from their personal physicians during the whole study period. The patients will be followed in a blinded manner for a total of 15 months. All patients that have not performed the 15 months visit when the updated protocol is implemented, will be asked to participate in the Extension Study Period which includes an additional visit at month 24.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 109 participants
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)
Primary Purpose: Treatment
Official Title: A Phase IIb, 2-Arm, Randomized, Double-blind, Placebo-Controlled, Multicentre Study to Optimize Diamyd® Therapy Administered Into Lymph Nodes Combined With Oral Vitamin D to Investigate the Impact on the Progression of Type 1 Diabetes
Actual Study Start Date : December 20, 2017
Actual Primary Completion Date : July 13, 2020
Actual Study Completion Date : April 27, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active arm
Patients will be assigned to receive i) three (3) intralymphatic injections with 4µg Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)
Biological: GAD-alum
Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD)
Other Name: Diamyd

Dietary Supplement: Vitamin D
Oil suspension of Vitamin D

Placebo Comparator: Placebo arm
Patients will be assigned to receive i) three (3) intralymphatic injections of Placebo for Diamyd (GAD-alum) on Days 30, 60, and 90 and; ii) oral Placebo for vitamin D once a day for 4 months (from Day 1 through Day 120)
Biological: Placebo for Diamyd (GAD-alum)
Alhydrogel® only

Dietary Supplement: Placebo for Vitamin D
Placebo oil suspension for Vitamin D




Primary Outcome Measures :
  1. Change in stimulated C-peptide during a MMTT [ Time Frame: Baseline and 15 months ]
    Change in C-peptide (Area Under the Curve [AUC]mean 0-120 min) during a Mixed Meal Tolerance Test (MMTT) between baseline to 15 months.


Secondary Outcome Measures :
  1. Change in IDAA1c [ Time Frame: Baseline and 15 months ]
    • Change in insulin-dose-adjusted HbA1c (IDAA1c)

  2. Change in HbA1c [ Time Frame: Baseline and 15 months ]
    • Change in HbA1c (mmol/mol)

  3. Change in insulin consumption [ Time Frame: Baseline and 15 months ]
    • Change in daily exogenous insulin consumption (IU)

  4. Change in glycemic variability/fluctuations [ Time Frame: Screening and 15 months ]
    • Change in glycemic variability/fluctuations (evaluated from data from continuous glucose monitoring FreeStyle LibrePro, FGM) over 14 day period.

  5. Proportion of patients with IDAA1c ≤ 9 [ Time Frame: 15 months ]
    • Proportion of patients with IDAA1c ≤ 9

  6. Stimulated maximum C-peptide above 0.2 nmol/L [ Time Frame: 15 months ]
    • Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L (0.6 ng/ml)

  7. Stimulated C-peptide above 0.2 nmol/L at 90 min [ Time Frame: 15 months ]
    • Proportion of patients with a stimulated 90min C-peptide level above 0.2 nmol/L (0.6 ng/ml)

  8. Number of hypoglycemias [ Time Frame: Baseline and 15 months ]
    • Number of self-reported episodes of severe hypoglycemia (Severe hypoglycemia defined as needing help from others and/or seizures and/or unconscious) (counts)

  9. Number of patients having at least 1 severe hypoglycemic event [ Time Frame: Baseline and 15 months ]
    • Number of patients having at least 1 severe hypoglycemic event (counts)

  10. • Change in maximum C-peptide [ Time Frame: Baseline and 15 months ]
    • Change in maximum C-peptide during MMTT (nmol/L)

  11. • Change in Fasting C-peptide [ Time Frame: Baseline and 15 months ]
    • Change in Fasting C-peptide (nmol/L)

  12. C-peptide levels during a MMTT [ Time Frame: 15 months ]
    • C-peptide measured at 30, 60, 90, and 120 minutes during MMTT (nmol/L) at 15 months

  13. Change in body weight and BMI [ Time Frame: Baseline and 15 months ]
    Change in body weight and BMI

  14. Injection site reactions [ Time Frame: 15 months ]
    • Injection site reactions

  15. Number of clinically significant abnormal results from laboratory measurements (haematology and clinical chemistry) and urinalysis. [ Time Frame: 15 months ]
    Number of clinically significant abnormal results from laboratory measurements (haematology and clinical chemistry) and urinalysis. (counts)

  16. Physical examination [ Time Frame: 15 months ]
    • Physical examinations, including neurological assessments

  17. GAD65A titer [ Time Frame: 15 months ]
    • GAD65A titer (IU/ml)

  18. Vital signs [ Time Frame: 15 months ]
    • Vital signs (blood pressure) (mmHg)

  19. Change in Quality of Life [ Time Frame: Baseline and 15 months ]
    • Change in QoL as measured by questionnaire EQ-5D-5L between baseline and Month 15.



Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. T1D according to the 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03345004


Locations
Show Show 18 study locations
Sponsors and Collaborators
Diamyd Medical AB
Investigators
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Principal Investigator: Johnny Ludvigsson, MD, Prof Universitetssjukhuset i Linköping
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Diamyd Medical AB
ClinicalTrials.gov Identifier: NCT03345004    
Other Study ID Numbers: DIAGNODE-2 (D/P2/17/6)
2017-001861-25 ( EudraCT Number )
First Posted: November 17, 2017    Key Record Dates
Last Update Posted: September 17, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Diamyd Medical AB:
Diamyd
Diabetes
Juvenile Diabetes
Diabetes Type 1
Type 1 Diabetes
Autoimmune Diabetes
Insulin Dependent Diabetes
Type 1 Diabetes Mellitus
rhGAD65
GAD65
GAD-Alum
Diabetes Mellitus
Diabetes Mellitus Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Vitamin D
Vitamins
Micronutrients
Cholecalciferol
Ergocalciferols
Additional relevant MeSH terms:
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Diabetes Mellitus
Diabetes Mellitus, Type 1
Metabolic Diseases
Glucose Metabolism Disorders
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Vitamin D
Ergocalciferols
Vitamins
Aluminum sulfate
Micronutrients
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents
Adjuvants, Immunologic
Immunologic Factors