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
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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 |
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 |

Arm | Intervention/treatment |
---|---|
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)
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Biological: Diamyd
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)
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Biological: Placebo for Diamyd
Alhydrogel® only 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)

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Ages Eligible for Study: | 12 Years to 24 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Informed consent given by patients and/or patient's parent(s) or legal acceptable representative(s) (guardian(s)) according to national regulations
- Type 1 Diabetes (T1D) according to the Amercian Diabetes Association (ADA) classification diagnosed ≤6 months at the time of screening
- Age: ≥12 and <25 years old
- 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)
- Positive for Glutamic Acid Decarboxylase isoform 65 (GAD65A) but < 50 000 IU/ml
- 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:
- oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
- combined (estrogen and progestogen containing)
- oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
- intrauterine device
- intrauterine hormone-releasing system (for example, progestin-releasing coil)
- bilateral tubal occlusion
- vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
- male partner using condom
- abstinence from heterosexual intercourse
For males of childbearing potential:
- condom (male)
- abstinence from heterosexual intercourse
Exclusion Criteria:
- Previous or current treatment with immunosuppressant therapy (although topical or inhaled steroids are accepted)
- Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
- Treatment with any oral or injected anti-diabetic medications other than insulin
- A history of anemia or significantly abnormal hematology results at screening
- A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
- Clinically significant history of acute reaction to vaccines or other drugs in the past
- 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.
- Participation in other clinical trials with a new chemical entity within the previous 3 months
- Inability or unwillingness to comply with the provisions of this protocol
- A history of alcohol or drug abuse
- A significant illness other than diabetes within 2 weeks prior to first dosing
- Known HIV or hepatitis
- 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)
- 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
- Deemed by the investigator not being able to follow instructions and/or follow the study protocol

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 |
Documents provided by Diamyd Medical AB:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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 |
Results First Posted: | January 9, 2023 |
Last Update Posted: | January 9, 2023 |
Last Verified: | April 2022 |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
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 |
Diabetes Mellitus Diabetes Mellitus, Type 1 Metabolic Diseases Glucose Metabolism Disorders Endocrine System Diseases Autoimmune Diseases Immune System Diseases Vitamin D |
Ergocalciferols Cholecalciferol Vitamins Micronutrients Physiological Effects of Drugs Bone Density Conservation Agents Calcium-Regulating Hormones and Agents |