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

NCT02464033 | Completed Phase 2 Results DMC

• 1 other identifier: EDCR IIa
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

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

Conditions

Diabetes Mellitus, Type 1

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

Outcome Measures

Primary Outcomes (8)

• 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

  1 months

• 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

  2 months

• 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.

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

• Number of Patients With Clinically Significant Laboratory Findings

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

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

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

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

  6 months

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

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

  15 months

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

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

  30 months

• 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

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

Secondary Outcomes (26)

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

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

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

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

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

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

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

  6 months

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

  15 months

Study Arms (1)

A

EXPERIMENTAL

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; Drug: Vitamin D; Drug: Etanercept

Interventions

GAD-Alum DRUG

Recombinant Human Glutamic Acid Decarboxylase (rhGAD65)

Also known as: Diamyd

A

Vitamin D DRUG

Also known as: Cholecalciferol

A

Etanercept DRUG

A

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• 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:

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Johnny Ludvigsson: lead
• Swedish Child Diabetes Foundation: collaborator
• Ostergotland County Council, Sweden: collaborator
• Diamyd Medical AB: collaborator

Study Sites (8)

Helsingborg Hospital

Helsingborg, Sweden

Location

Linköping University Hospital

Linköping, Sweden

Location

Lund University Hospital

Lund, Sweden

Location

Skåne University Hospital, UMAS

Malmo, Sweden

Location

Örebro University Hospital

Örebro, Sweden

Location

Sachsska, Södersjukhuset

Stockholm, Sweden

Location

Uddevalla Hospital

Uddevalla, Sweden

Location

Västerås Hospital

Västerås, Sweden

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases

Interventions

Vitamin D; Cholecalciferol; Etanercept

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholestenes; Cholestanes; Sterols; Membrane Lipids; Lipids; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Johnny Ludvigsson, MD, PhD, Prof Linkoeping University
• Organization: Linkoeping University

Johnny.Ludvigsson@liu.se

+46 13 28 68 54

Study Officials

• Johnny Ludvigsson, MD,PhD,Prof

  Linkoeping University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD, Professor

Study Record Dates

• First Submitted: May 19, 2015
• First Posted: June 8, 2015
• Study Start: May 1, 2015
• Primary Completion: February 25, 2019
• Study Completion: February 25, 2019
• Last Updated: March 29, 2021
• Results First Posted: September 25, 2019

Record last verified: 2021-03

Locations

SE (8)