Diamyd Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes

Diamyd Medical AB109 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

109

Conditions

Diabetes Mellitus, Type 1 Diabetes Mellitus

Eligibility

Sex: ALLMin age: 12 YearsMax age: 24 Years

Medical Language ↔ Plain English

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

Locations (18)

Diabetes Centre, Institute of Clinical and Experimental Medicine

Prague, Czechia

Department of Paediatrics, University Hospital Motol

Prague, Czechia

Diabeter Rotterdam

Rotterdam, Netherlands

Adult and Pediatrics Endocrinology and Diabetology, Hospital Universitario Cruces

Barakaldo, Spain

Adult Endocrinology and Diabetology, Hospital vall D' Hebrón

Barcelona, Spain

Pediatrics Endocrinology and Diabetology, Hospital Vall D'Hebrón

Barcelona, Spain

Adult Endocrinology and Diabetology, Hospital Ramón y Cajal

Madrid, Spain

Adult Endocrinology and Diabetology, Hospital Carlos Haya

Málaga, Spain

Pediatrics Endocrinology and Diabetology, Hospital Materno-Ifantil

Málaga, Spain

Adult Endocrinology and Diabetology, Hospital Macarena

Seville, Spain

...and 8 more locations

Outcomes

Primary Outcomes

Change in Stimulated C-peptide During a MMTT

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.

Time frame: Baseline and 15 months

Secondary Outcomes

Change in IDAA1c

Change in insulin-dose-adjusted HbA1c (IDAA1c)

Time frame: Baseline and 15 months

Change in HbA1c

Change in HbA1c (mmol/mol)

Time frame: Baseline and 15 months

Change in Insulin Consumption

Change in daily exogenous insulin consumption (IU)

Time frame: Baseline and 15 months

Change in Glycemic Variability/Fluctuations

Change in glycemic variability/fluctuations (evaluated from data from continuous glucose monitoring FreeStyle LibrePro, FGM) over 14 day period.

Time frame: Screening and 15 months

Percentage of Patients With IDAA1c ≤ 9

Percentage of patients with IDAA1c ≤ 9

Time frame: 15 months

Stimulated Maximum C-peptide Above 0.2 Nmol/L

Percentage of patients with a stimulated maximum C-peptide level above 0.2 nmol/L (0.6 ng/ml)

Time frame: 15 months

Stimulated C-peptide Above 0.2 Nmol/L at 90 Min

Percentage of patients with a stimulated 90min C-peptide level above 0.2 nmol/L (0.6 ng/ml)

Time frame: 15 months

Number of Hypoglycemias

Number of self-reported episodes of severe hypoglycemia (Severe hypoglycemia defined as needing help from others and/or seizures and/or unconscious) (counts)

Time frame: Baseline and 15 months

Number of Patients Having at Least 1 Severe Hypoglycemic Event

Number of patients having at least 1 severe hypoglycemic event (counts)

Time frame: Baseline and 15 months

Change in Maximum C-peptide

Change in maximum C-peptide during MMTT (nmol/L)

Time frame: Baseline and 15 months

Change in Fasting C-peptide

Change in Fasting C-peptide (nmol/L)

Time frame: Baseline and 15 months

C-peptide Levels During a MMTT

C-peptide measured at 30, 60, 90, and 120 minutes during MMTT (nmol/L) at 15 months

Time frame: 15 months

Change in Body Weight

Change in body weight (kg)

Time frame: Baseline and 15 months

Injection Site Reactions

Injection site reactions

Time frame: 15 months

Number of Clinically Significant Abnormal Results From Laboratory Measurements (Haematology and Clinical Chemistry) and Urinalysis.

Number of clinically significant abnormal results from laboratory measurements (haematology and clinical chemistry) and urinalysis. (counts)

Time frame: 15 months

Number of Clinically Significant Abnormal Results From Physical and Neurological Examinations

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"

Time frame: 15 months

GAD65A Titer

GAD65A titer (IU/ml)

Time frame: Baseline and 15 months

Number of Clinically Significant Abnormal Results in Vital Signs

Vital signs (blood pressure) (mmHg)

Time frame: 15 months

Change in Quality of Life (QoL)

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.

Time frame: Baseline and 15 months

Change in Body Mass Index (BMI)

Change in BMI (kg/m2)

Time frame: Baseline and 15 months

Diamyd Administered Into Lymph Nodes in Combination With Vitamin D in Type 1 Diabetes

Overview

Conditions

Interventions

Eligibility

Locations (18)

Outcomes

Primary Outcomes

Secondary Outcomes