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EDCR Study - Etanercept Diamyd Combination Regimen -Open Trial to Evaluate Safety in Children With Type 1 Diabetes

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ClinicalTrials.gov Identifier: NCT02464033
Recruitment Status : Active, not recruiting
First Posted : June 8, 2015
Last Update Posted : March 7, 2018
Sponsor:
Collaborators:
Swedish Child Diabetes Foundation
Ostergotland County Council, Sweden
Diamyd Medical AB
Information provided by (Responsible Party):
Johnny Ludvigsson, Linkoeping University

Brief Summary:

The objectives of this study is to:

  • Evaluate the tolerability of a combination therapy with Diamyd, vitamin D and etanercept
  • Evaluate how the above mentioned treatments influence the immune system and endogenous insulin secretion

Condition or disease Intervention/treatment Phase
Diabetes Mellitus, Type 1 Drug: GAD-Alum Drug: Vitamin D Drug: Etanercept Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open Label Trial to Evaluate the Tolerability of a Combination Therapy Consisting of GAD-alum (Diamyd®), Etanercept and Vitamin D in Children and Adolescents Newly Diagnosed With Type 1 Diabetes
Study Start Date : May 2015
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: A
All patients will from Day 1 receive 2 000 IU vitamin D per os per day during 15 months, and from Days 1-90 receive etanercept (Enbrel) injected subcutaneously 0.8 mg/kg body weight (max 50 mg) once a week, and receive 2 subcutaneous injections of 20 μg Diamyd in a prime-and-boost regimen on Days 30 and 60.
Drug: GAD-Alum
Other Name: Diamyd

Drug: Vitamin D
Drug: Etanercept



Primary Outcome Measures :
  1. Reactions of the injection site as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    Reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching)

  2. To Evaluate the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    Incidence of infection as an assessment of the tolerability of a combination therapy

  3. Number of adverse events and number of participants with adverse events as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    Number of adverse events and number of participants with adverse events

  4. Number of serious adverse events and number of participants with serious adverse events as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    Number of serious adverse events and number of participants with serious adverse events

  5. Physical examinations, including neurological assessments as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    Physical examinations, including neurological assessments

  6. Laboratory measurements as an assessment of the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    Laboratory measurements (biochemistry and haematology), including Calcium and Vitamin D in serum

  7. GAD65AB titer measured to Evaluate the tolerability of a combination therapy with Diamyd, Vitamin D and etanercept at Month 6 (main study Period) [ Time Frame: 6 months ]
    GAD65AB titer (GADA)


Secondary Outcome Measures :
  1. Change in immune system markers from baseline to Month 6 (main study period) and subsequent visits during the extension study period [ Time Frame: 6 months, 9, 15 and 30 months ]
    Inflammatory markers, (e.g. TNF-alfa, IL-1 beta, IL-2, IL-17); Th2-deviation of cell-mediated immune response seen e.g. as increased ratio IL-5,10, 13 in comparison with IFN-gamma, TNF-alfa, IL-1 beta and IL-17; Regulatory T-cells

  2. C-peptide: Area Under the Curve (mean 0-120 min) during an MMTT, change from baseline [ Time Frame: 6 months, 9, 15 and 30 months ]
  3. Proportion of patients with a stimulated maximum C-peptide level above 0.2 nmol/L [ Time Frame: 6 months, 9, 15 and 30 months ]
  4. Hemoglobin A1c (HbA1c), change from baseline [ Time Frame: 6 months, 9, 15 and 30 months ]
  5. Exogenous insulin dose per kg body weight and 24 hours, change from baseline [ Time Frame: 6 months, 9, 15 and 30 months ]
  6. C-peptide: Fasting, 90 minute value, change from baseline [ Time Frame: 6 months, 9, 15 and 30 months ]


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Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Informed consent given by patients and parent(s)/legal guardian(s)
  2. Type 1 diabetes according to the ADA classification, diagnosed within the previous 100 days at the time of screening
  3. Age 8.00 -17.99 years at time of screening
  4. Fasting C-peptide at time of screening ≥0.12 nmol/L
  5. Positive for GADA but < 50 000 Units
  6. Menarchal females must agree to avoid pregnancy and have a negative urine pregnancy test
  7. Immunity against Varicella, either through previous infection or vaccination
  8. Patients must follow the Swedish vaccination programme
  9. Patients of childbearing potential must agree to using adequate contraception, if sexually active, until 1 year after the last administration of GAD-alum and etanercept. Adequate contraception is as follows:

For females of childbearing potential:

  1. oral (except low-dose gestagen (lynestrenol and norestisteron), injectable, or implanted hormonal contraceptives (females)
  2. intrauterine device (females)
  3. intrauterine system (for example, progestin-releasing coil) (females)
  4. vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)

For males of childbearing potential:

a. Condom (male)

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 (especially hypoglycemic agents) other than insulin
  4. Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
  5. A history of hypercalcemia
  6. A history of anaemia or significantly abnormal haematology results at screening
  7. A history of epilepsy, head trauma or cerebro-vascular accident, or clinical features of continuous motor unit activity in proximal muscles
  8. Clinically significant history of acute reaction to vaccines or other drugs in the past
  9. Treatment with any vaccine within 4 months prior to planned first administration of GAD-Alum or planned treatment with vaccine up to 4 months after the last injection with GAD-Alum, including influenza vaccine
  10. Participation in other clinical trials with a new chemical entity within the previous 3 months
  11. Inability or unwillingness to comply with the provisions of this protocol
  12. A history of alcohol or drug abuse
  13. A significant illness other than diabetes within 2 weeks prior to first dosing
  14. Known human immunodeficiency virus (HIV)
  15. Prior or active viral hepatitis B or C infection
  16. Females who are lactating or pregnant (for females who have started menstruating the possibility of pregnancy must be excluded by urine βHCG on-site within 24 hours prior to the GAD-Alum and etanercept administration, respectively)
  17. Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last GAD-Alum and etanercept administration, respectively
  18. Presence of associated serious disease or condition, including active skin infections that preclude subcutaneous injection, which in the opinion of the investigator makes the patient non-eligible for the study.
  19. Deemed by the investigator not being able to follow instructions and/or follow the study protocol
  20. Active infection, including chronic and local infection or a history of previous tendency to serious infections, recent or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, or known infection with active EBV or CMV
  21. Hypersensivity to the active substance in Enbrel (etanercept) or other ingredients in Enbrel
  22. Active or inactive (latent) tuberculosis (TBC) at screening
  23. History of malignancy or significant cardiovascular disease
  24. Current or history of leukopenia, anemia and/or thrombocytopeni
  25. Liver disease (clinical or hepatic enzymes >3 times the upper limit of normal (ULN))
  26. Renal insufficiency (clinical or creatinine >3 times the upper limit of normal (ULN))
  27. MS, undefined neurologic condition or known SLE, or anti-nuclear or known doublestranded DNA antibody positivity
  28. Arrhythmia
  29. Pancreatitis
  30. Vitamin D serum levels >100 nmol/L at screening

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): NCT02464033


Locations
Sweden
Helsingborg Hospital
Helsingborg, Sweden
Linköping University Hospital
Linköping, Sweden
Lund University Hospital
Lund, Sweden
Skåne University Hospital, UMAS
Malmö, Sweden
Sachsska, Södersjukhuset
Stockholm, Sweden
Uddevalla Hospital
Uddevalla, Sweden
Västerås Hospital
Västerås, Sweden
Örebro University Hospital
Örebro, Sweden
Sponsors and Collaborators
Johnny Ludvigsson
Swedish Child Diabetes Foundation
Ostergotland County Council, Sweden
Diamyd Medical AB
Investigators
Principal Investigator: Johnny Ludvigsson, MD,PhD,Prof Linkoeping University

Responsible Party: Johnny Ludvigsson, MD, PhD, Professor, Linkoeping University
ClinicalTrials.gov Identifier: NCT02464033     History of Changes
Other Study ID Numbers: EDCR IIa
First Posted: June 8, 2015    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018

Keywords provided by Johnny Ludvigsson, Linkoeping University:
Diamyd
Diabetes
Juvenile Diabetes
Diabetes Type 1
Type 1 Diabetes
Autoimmune Diabetes
Insulin Dependent Diabetes
Type 1 Diabetes MellitusType 1 Diabetes Mellitus
rhGAD65
GAD65
GAD-Alum
Diabetes Mellitus
Diabetes mellitus Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Vitamin D
Etanercept

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Vitamins
Vitamin D
Ergocalciferols
Etanercept
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors