Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03345004
Recruitment Status : Active, not recruiting
First Posted : November 17, 2017
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Diamyd Medical AB

Tracking Information
First Submitted Date  ICMJE November 1, 2017
First Posted Date  ICMJE November 17, 2017
Last Update Posted Date October 17, 2019
Actual Study Start Date  ICMJE December 20, 2017
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 13, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03345004 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 13, 2017)
  • 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)
  • 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)
  • • Change in maximum C-peptide [ Time Frame: Baseline and 15 months ]
    • Change in maximum C-peptide during MMTT (nmol/L)
  • 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
  • • Change in Fasting C-peptide [ Time Frame: Baseline and 15 months ]
    • Change in Fasting C-peptide (nmol/L)
  • Change in HbA1c [ Time Frame: Baseline and 15 months ]
    • Change in HbA1c (mmol/mol)
  • Change in insulin consumption [ Time Frame: Baseline and 15 months ]
    • Change in daily exogenous insulin consumption (IU)
  • Change in IDAA1c [ Time Frame: Baseline and 15 months ]
    • Change in insulin-dose-adjusted HbA1c (IDAA1c)
  • Proportion of patients with IDAA1c ≤ 9 [ Time Frame: 15 months ]
    • Proportion of patients with IDAA1c ≤ 9
  • 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.
  • 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)
  • 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)
  • Change in Rate of hypoglycemic events [ Time Frame: Baseline and 15 months ]
    • Change in Rate of hypoglycemic events
  • Injection site reactions [ Time Frame: 15 months ]
    • Injection site reactions
  • Adverse Events [ Time Frame: 15 months ]
    • Occurrence of AEs
  • Laboratory analysis of safety parameters [ Time Frame: 15 months ]
    • Laboratory measurements (hematology and clinical chemistry)
  • Urine analysis [ Time Frame: 15 months ]
    • Urine analysis (microalbuminuria, creatinine)
  • Physical examination [ Time Frame: 15 months ]
    • Physical examinations, including neurological assessments
  • GAD65A titer [ Time Frame: 15 months ]
    • GAD65A titer (IU/ml)
  • Vital signs [ Time Frame: 15 months ]
    • Vital signs (blood pressure) (mmHg)
  • Total serum Immunoglobulin E [ Time Frame: 15 months ]
    • Total serum Immunoglobulin E (IgE) (IU/ml).
  • Concentrations of serum autoantibodies [ Time Frame: 15 months ]
    • Concentrations of serum autoantibodies towards GAD65 and IA 2 (IU/ml).
  • Concentrations of serum autoantibodies isotypes [ Time Frame: 15 months ]
    • Concentrations of serum autoantibody isotypes towards GAD65 (IU/ml).
  • Cytokine secretion patterns of PBMCs [ Time Frame: 15 months ]
    • Secretion of cytokines interleukin (IL)-1, IL-2, IL-5, IL-13, IL-10, IL-17, interferon (IFN)γ, and tumour necrosis factor (TNF)α by peripheral blood mononuclear cells (PBMCs) upon stimulation with GAD65.
  • Number of PMBCs secreting specific cytokines [ Time Frame: 15 months ]
    • Number of PBMCs secreting IL-10, IL-4 and/or IFNγ upon stimulation with GAD65 measured by enzyme linked immunosorbent spot forming cell assay (ELISPOT)
  • Proliferation of PBMCs [ Time Frame: 15 months ]
    • Proliferation of PBMCs upon stimulation with GAD65.
  • Flow cytometric analysis of PBMC subsets [ Time Frame: 15 months ]
    • FACS analysis of PBMC subsets.
  • Exploratory immunological characterization [ Time Frame: 15 months ]
    • Further exploratory immunological characterization.
  • 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.
  • Quality adjusted life years [ Time Frame: 15 months ]
    • Quality adjusted life years (QALYs) based on the EQ-5D-5L questionnaire.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 15, 2019)
  • Change in stimulated C-peptide during a MMTT [ Time Frame: Baseline and 24 months ]
    Change in C-peptide (Area Under the Curve [AUC]mean 0-120 min) during a Mixed Meal Tolerance Test (MMTT) between baseline to 24 months.
  • Change in HbA1c [ Time Frame: Baseline and 24 months ]
    Change in HbA1c (mmol/mol)
  • Change in insulin consumption [ Time Frame: Baseline and 24 months ]
    Change in daily exogenous insulin consumption (IU)
  • Change in Fasting C-peptide [ Time Frame: Baseline and 24 months ]
    Change in Fasting C-peptide (nmol/L)
  • Change in glycemic variability/fluctuations [ Time Frame: Screening and 24 months ]
    Change in glycemic variability/fluctuations (evaluated from data from continuous glucose monitoring FreeStyle LibrePro, FGM) over 14 day period.
  • Change in Rate of hypoglycemic events [ Time Frame: Baseline and 24 months ]
    Change in Rate of hypoglycemic events
  • Number of patients having at least 1 severe hypoglycemic event [ Time Frame: Baseline and 24 months ]
    Number of patients having at least 1 severe hypoglycemic event (counts)
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE GAD-Alum (Diamyd) Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes
Official Title  ICMJE 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
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Condition  ICMJE
  • 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
Intervention  ICMJE
  • Biological: GAD-alum
    Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD)
    Other Name: Diamyd
  • Dietary Supplement: Vitamin D
    Oil suspension of Vitamin D
  • Biological: Placebo for Diamyd (GAD-alum)
    Alhydrogel® only
  • Dietary Supplement: Placebo for Vitamin D
    Placebo oil suspension for Vitamin D
Study Arms  ICMJE
  • 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)
    Interventions:
    • Biological: GAD-alum
    • Dietary Supplement: 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)
    Interventions:
    • Biological: Placebo for Diamyd (GAD-alum)
    • Dietary Supplement: Placebo for Vitamin D
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: May 8, 2019)
109
Original Estimated Enrollment  ICMJE
 (submitted: November 13, 2017)
80
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date August 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 24 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czechia,   Netherlands,   Spain,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03345004
Other Study ID Numbers  ICMJE DIAGNODE-2 (D/P2/17/6)
2017-001861-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Diamyd Medical AB
Study Sponsor  ICMJE Diamyd Medical AB
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Johnny Ludvigsson, MD, Prof Universitetssjukhuset i Linköping
PRS Account Diamyd Medical AB
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP