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Diabetes Mellitus, Type 1Phase 2NCT02464033

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

A Phase 2 study testing GAD-Alum, Vitamin D and Etanercept in people with Diabetes Mellitus, Type 1, run by Johnny Ludvigsson at 8 sites in Sweden.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 8 to 18 years
Conditions the study is for
Diabetes Mellitus, Type 1
What is being tested?
GAD-Alum, Vitamin D and Etanercept
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
8 sitesSweden
Study dates
May 2015to 25 Feb 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Informed consent given by patients and parent(s)/legal guardian(s)
  • Type 1 diabetes according to the ADA classification, diagnosed within the previous 100 days at the time of screening
  • Age 8.00 -17.99 years at time of screening
  • Fasting C-peptide at time of screening ≥0.12 nmol/L
  • Positive for GADA but < 50 000 Units
  • Menarchal females must agree to avoid pregnancy and have a negative urine pregnancy test
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  • Immunity against Varicella, either through previous infection or vaccination
  • Patients must follow the Swedish vaccination programme
  • 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:
  • oral (except low-dose gestagen (lynestrenol and norethisterone), injectable, or implanted hormonal contraceptives (females)
  • intrauterine device (females)
  • intrauterine system (for example, progestin-releasing coil) (females)
  • vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)
  • For males of childbearing potential:
  • Condom (male)

Who cannot join

  • 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 (especially hypoglycemic agents) other than insulin
  • Treatment with Vitamin D, marketed or not, or unwilling to abstain from such medication during the trial
  • A history of hypercalcemia
  • A history of anaemia or significantly abnormal haematology results at screening
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  • A history of epilepsy, head trauma or cerebro-vascular 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 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
  • 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 human immunodeficiency virus (HIV)
  • Prior or active viral hepatitis B or C infection
  • 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)
  • Males or females not willing to use adequate contraception, if sexually active, until 1 year after the last GAD-Alum and etanercept administration, respectively
  • 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.
  • Deemed by the investigator not being able to follow instructions and/or follow the study protocol
  • 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
  • Hypersensitivity to the active substance in Enbrel (etanercept) or other ingredients in Enbrel
  • Active or inactive (latent) tuberculosis (TBC) at screening
  • History of malignancy or significant cardiovascular disease
  • Current or history of leukopenia, anemia and/or thrombocytopenia
  • Liver disease (clinical or hepatic enzymes >3 times the upper limit of normal (ULN))
  • Renal insufficiency (clinical or creatinine >3 times the upper limit of normal (ULN))
  • MS, undefined neurologic condition or known SLE, or anti-nuclear or known doublestranded DNA antibody positivity
  • Arrhythmia
  • Pancreatitis
  • Vitamin D serum levels >100 nmol/L at screening

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Sweden8 sites

  • Helsingborg Hospital

    Helsingborg

  • Linköping University Hospital

    Linköping

  • Lund University Hospital

    Lund

  • Skåne University Hospital, UMAS

    Malmö

  • Örebro University Hospital

    Örebro

  • Sachsska, Södersjukhuset

    Stockholm

  • Uddevalla Hospital

    Uddevalla

  • Västerås Hospital

    Västerås

Other trials in Sweden

About this study

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

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
Being tested
GAD-Alum, Vitamin D, Etanercept
Keywords
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
Medical subject headings
Diabetes Mellitus, Type 1, Diabetes Mellitus, Glucose Metabolism Disorders, Metabolic Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GAD-AlumDrug

    Also called Diamyd

    Recombinant Human Glutamic Acid Decarboxylase (rhGAD65)

  • Vitamin DDrug

    Also called Cholecalciferol

  • EtanerceptDrug

Study groups in NCT02464033
Study groupRoleWhat they receive
AExperimentalAll 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.
Receives: Drug: GAD-Alum; Drug: Vitamin D; Drug: Etanercept

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability

    Number of patients with reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching, Other). Inspection of injection site 60 minutes after GAD-Alum injection by investigator or nurse

    Measured: 1 months

  2. Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability

    Number of patients with reactions of the injection site (Erythema, Oedema, Haematoma, Tenderness, Pain, Itching, Other). Inspection of injection site 60 minutes after GAD-Alum injection by investigator or nurse

    Measured: 2 months

  3. Number of Patients With Any Abnormal Findings From Physical Examinations After Baseline

    Number of patients with any abnormal findings from physical examinations after baseline, including neurological assessments as an assessment of tolerability.

    Measured: Month 1, 2, 3, 6, 9, 15 and 30

  4. Number of Patients With Clinically Significant Laboratory Findings

    Number of patients with clinically significant laboratory findings, laboratory measurements as an assessment of the tolerability

    Measured: Month 1, 2, 3, 6, 9, 15 and 30

  5. GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)

    GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000

    Measured: 6 months

  6. GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)

    GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000

    Measured: 15 months

  7. GAD65AB Titer Measured to Evaluate the Tolerability (Main Study Period)

    GAD65AB titer (GADA) change from baseline. GAD65AB = Antibodies to GAD with molecular mass 65000

    Measured: 30 months

  8. Number of Patients With an Infection Reported as Adverse Event Related to Study Treatment

    Number of patients with an infection reported as Adverse Event related to study treatment (GAD-Alum and/or Etanercept),as an assessment of the tolerability

    Measured: Month 1, 2, 3, 6, 9, 15 and 30

Secondary outcomes (26)

  1. C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline

    Weighted mean C-peptide: (AUC mean 0-120 min) during an MMTT, change from baseline to 6 months. MMTT=Mixed Meal Tolerance Test

    Measured: Baseline and 6 months at 0, 30, 60, 90 and 120 minutes post-dose

  2. C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline

    Weighted mean C-peptide: (AUC mean 0-120 min) during an MMTT, change from baseline to 15 months

    Measured: Baseline and 15 months at 0, 30, 60, 90 and 120 minutes post-dose

  3. C-peptide: Area Under the Curve (AUC 0-120 Min) During an MMTT, Change From Baseline

    Weighted mean C-peptide: (AUC mean 0-120 min) during an MMTT, change from baseline to 30 months

    Measured: Baseline and 30 months at 0, 30, 60, 90 and 120 minutes post-dose

  4. Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L

    Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 6 months

    Measured: 6 months

  5. Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L

    Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 15 months

    Measured: 15 months

  6. Number of Patients With a Stimulated Maximum C-peptide Level Above 0.2 Nmol/L

    Number of patients with a stimulated maximum C-peptide level above 0.2 nmol/L at 30 months

    Measured: 30 months

  7. Hemoglobin A1c (HbA1c), Change From Baseline

    Hemoglobin A1c (HbA1c), change from baseline to 6 months

    Measured: Baseline and 6 months

  8. Hemoglobin A1c (HbA1c), Change From Baseline

    Hemoglobin A1c (HbA1c), change from baseline to 15 months

    Measured: Baseline and 15 months

  9. Hemoglobin A1c (HbA1c), Change From Baseline

    Hemoglobin A1c (HbA1c), change from baseline to 30 months

    Measured: Baseline and 30 months

  10. Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline

    Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline

    Measured: Baseline and 6 months

  11. Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline

    Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline

    Measured: Baseline and 15 months

  12. Exogenous Insulin Dose Per kg Body Weight and 24 Hours, Change From Baseline

    Exogenous 24-hour insulin dose per kg body weight and 24 hours average, change from baseline

    Measured: Baseline and 30 months

  13. C-peptide: Stimulated, 90 Minute Value, Change From Baseline

    C-peptide: Stimulated, 90 minute value, change from baseline to 6 months

    Measured: Baseline and 6 months

  14. C-peptide: Stimulated, 90 Minute Value, Change From Baseline

    C-peptide: Stimulated, 90 minute value, change from baseline to 15 months

    Measured: Baseline and 15 months

  15. C-peptide: Stimulated, 90 Minute Value, Change From Baseline

    C-peptide: Stimulated, 90 minute value, change from baseline to 30 months

    Measured: Baseline and 30 months

  16. C-peptide Fasting Concentration, Change From Baseline

    C-peptide: Fasting concentration, change from baseline to 6 months

    Measured: Baseline and 6 months

  17. C-peptide Fasting Concentration, Change From Baseline

    C-peptide: Fasting, concentration, change from baseline to 15 months

    Measured: Baseline and 15 months

  18. C-peptide Fasting Concentration, Change From Baseline

    C-peptide: Fasting, concentration, change from baseline to 30 months

    Measured: Baseline and 30 months

  19. Spontaneous IL-17a Secretion

    Spontaneous IL-17a secretion at baseline, 6 months, 9 months, 15 months and 30 months

    Measured: Baseline, 6 months, 9 months, 15 months and 30 months

  20. GAD65-induced IL-4 Secretion

    GAD65-induced IL-4 secretion at baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

  21. GAD65-induced IL-13 Secretion

    GAD65-induced IL-13 secretion at baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

  22. GAD65-induced IFN-gamma Secretion

    GAD65-induced IFN-gamma secretion at baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

  23. GAD65-induced TNF-alpha Secretion

    GAD65-induced TNF-alpha secretion at baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

  24. GAD65-induced GM-CSF Secretion

    GAD65-induced GM-CSF secretion baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

  25. GAD65-induced MIP-1b Secretion

    GAD65-induced MIP-1b secretion at baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

  26. GAD65-induced MCP-1 Secretion

    GAD65-induced MCP-1 secretion at baseline, 6 months, 9 months, 15 months, 30 months

    Measured: Baseline, 6 months, 9 months, 15 months, 30 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Jun 2015 (estimated)
  2. Study startMay 2015
  3. Primary completion25 Feb 2019
  4. Study completion25 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02464033
Sponsor's protocol ID
EDCR IIa
Status last verified
Mar 2021
First submitted
19 May 2015
Last updated
29 Mar 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GAD-Alum, Vitamin D and Etanercept in people with Diabetes Mellitus, Type 1, run by Johnny Ludvigsson at 8 sites in Sweden.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Reactions of the Injection Site as an Assessment of the Tolerability (time frame: 1 months). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02464033.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2021.

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