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
Results First Posted : January 9, 2023
Last Update Posted : January 9, 2023
|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: Diamyd Dietary Supplement: Vitamin D Biological: Placebo for Diamyd Dietary Supplement: Placebo for Vitamin D||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||109 participants|
|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)|
|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|
Active Comparator: Active arm
Patients will be assigned to receive i) three (3) intralymphatic injections with Recombinant human Glutamic Acid Decarboxylase adsorbed to Alhydrogel (Diamyd) on Days 30, 60, and 90 and; ii) oral vitamin D 2000 IU/daily for 4 months (from Day 1 through Day 120)
Alhydrogel®-formulated recombinant human glutamic acid decarboxylase (rhGAD65)
Other Name: GAD-alum
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 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
Dietary Supplement: Placebo for Vitamin D
Placebo oil suspension for Vitamin D
- Change in Stimulated C-peptide During a MMTT [ Time Frame: Baseline and 15 months ]Change in C-peptide between Baseline and 15 Months. C-peptide was measured by Area Under the Curve [AUC] at 0-120 min during a Mixed Meal Tolerance Test (MMTT) and divided by 120 min. The results are given as the ratio (back-transformed from log-scale) between 15 Months and Baseline as predicted by the MMRM (Mixed Model Repeated Measures) model.
- Change in IDAA1c [ Time Frame: Baseline and 15 months ]Change in insulin-dose-adjusted HbA1c (IDAA1c)
- 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 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.
- Percentage of Patients With IDAA1c ≤ 9 [ Time Frame: 15 months ]Percentage of patients with IDAA1c ≤ 9
- Stimulated Maximum C-peptide Above 0.2 Nmol/L [ Time Frame: 15 months ]Percentage 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 ]Percentage of patients with a stimulated 90min C-peptide level above 0.2 nmol/L (0.6 ng/ml)
- 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 Maximum C-peptide [ Time Frame: Baseline and 15 months ]Change in maximum C-peptide during MMTT (nmol/L)
- Change in Fasting C-peptide [ Time Frame: Baseline and 15 months ]Change in Fasting C-peptide (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 Body Weight [ Time Frame: Baseline and 15 months ]Change in body weight (kg)
- Injection Site Reactions [ Time Frame: 15 months ]Injection site reactions
- 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)
- Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations [ Time Frame: 15 months ]
Physical examination (general appearance including skin, mouth, throat, cardiovascular, abdomen, lymphatic glands, and neurological/musculoskeletal [including reflexes]).
Standardised clinical neurological examination including extremity reflexes, Romberg, Walk on a line, 2 meters, Standing on 1 leg, left and right, 15 seconds per leg, Finger-nose, Mimic, Babinski reflex.
The outcome of the assessments was recored as "normal" or "abnormal"
- GAD65A Titer [ Time Frame: Baseline and 15 months ]GAD65A titer (IU/ml)
- Number of Clinically Significant Abnormal Results in Vital Signs [ Time Frame: 15 months ]Vital signs (blood pressure) (mmHg)
- Change in Quality of Life (QoL) [ Time Frame: Baseline and 15 months ]Change in QoL as measured by the standardised measure of health questionnaire EQ-5D-5L between baseline and Month 15. The EQ-5D-5L is based on 5 questions rated at 5 levels indicating from no problem (level 1) to extreme problems (level 5) regarding current state of mobility, self-care, activity, pain and anxiety. The outcome is presented as a weighted index value, where 1 is the best possible health and 0 represents being dead.
- Change in Body Mass Index (BMI) [ Time Frame: Baseline and 15 months ]Change in BMI (kg/m2)
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
|Principal Investigator:||Johnny Ludvigsson, MD, Prof||Universitetssjukhuset i Linköping|