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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02293837




Registration number
NCT02293837
Ethics application status
Date submitted
13/11/2014
Date registered
18/11/2014

Titles & IDs
Public title
Tocilizumab (TCZ) in New-onset Type 1 Diabetes
Scientific title
Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)
Secondary ID [1] 0 0
DAIT ITN058AI
Universal Trial Number (UTN)
Trial acronym
EXTEND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes Mellitus 0 0
New-onset Type 1 Diabetes Mellitus 0 0
T1DM 0 0
T1D 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tocilizumab (TCZ)
Treatment: Drugs - Placebo
Other interventions - Standard of Care

Experimental: Tocilizumab (TCZ) + SOC - Subjects will receive intravenous (IV) infusions of either 8.0 mg/kg (body weight =30 kg) or 10.0 mg/kg (body weight \<30kg) tocilizumab every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines \[Standard of Care, SOC\])

Placebo comparator: Tocilizumab Placebo Group + SOC - Subjects will receive IV infusions of either 8.0 mg/kg (body weight = 30kg) or 10.0 mg/kg (body weight \<30kg) placebo every 4 weeks for 24 weeks. Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines \[Standard of Care, SOC\])


Treatment: Drugs: Tocilizumab (TCZ)
Subjects assigned to this group will receive tocilizumab intravenous (IV) infusions of either 8.0 mg/kg (body weight = 30kg) or 10.0 mg/kg (body weight \<30kg) every 4 weeks for 24 weeks.

Treatment: Drugs: Placebo
Subjects assigned to this group will receive placebo intravenous (IV) infusions of either 8.0 mg/kg (body weight = 30kg) or 10.0 mg/kg (body weight \<30kg) every 4 weeks for 24 weeks.

Other interventions: Standard of Care
Participants will also receive standard intensive diabetes management (in accordance with the American Diabetes Association guidelines \[Standard of Care, SOC\])
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC) in Pediatric Participants
Timepoint [1] 0 0
Baseline (Pre-treatment) to Week 52
Secondary outcome [1] 0 0
Change From Baseline in 2-Hour C-peptide Mean Area Under the Curve (mAUC)
Timepoint [1] 0 0
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Secondary outcome [2] 0 0
2-Hour C-peptide Mean Area Under the Curve (mAUC), Mixed Model
Timepoint [2] 0 0
Baseline (Pre-treatment), Weeks 12, 24, 39, 52, 78, and 104
Secondary outcome [3] 0 0
Change From Baseline in 4-Hour C-peptide Mean Area Under the Curve (mAUC)
Timepoint [3] 0 0
Baseline (Pre-treatment) to Weeks 52 and 104
Secondary outcome [4] 0 0
Change From Baseline in Average Insulin Use in Units Per Kilogram Body Weight Per Day
Timepoint [4] 0 0
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Secondary outcome [5] 0 0
Change From Baseline in Average Insulin Use Per Kg, Mixed Model
Timepoint [5] 0 0
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Secondary outcome [6] 0 0
Change From Baseline in Hemoglobin A1c
Timepoint [6] 0 0
Baseline (Pre-treatment) to Weeks 24, 52, and 104
Secondary outcome [7] 0 0
Change From Baseline in Hemoglobin A1C (HbA1c) Level in Participants, Mixed Model
Timepoint [7] 0 0
Baseline (Pre-treatment) to Weeks 12, 24, 39, 52, 78, and 104
Secondary outcome [8] 0 0
Number of Participants Who Experienced at Least One Major Hypoglycemic Event After Treatment Initiation
Timepoint [8] 0 0
Day 0 (Treatment Initiation) to Weeks 52 and 104
Secondary outcome [9] 0 0
Number of Participants Who Experienced Infusion-Related Adverse Events
Timepoint [9] 0 0
Day 0 (Treatment Initiation) to Week 52
Secondary outcome [10] 0 0
Number of Participants Who Experienced Hypersensitivity Adverse Events
Timepoint [10] 0 0
Day 0 (Treatment Initiation) to Week 52

Eligibility
Key inclusion criteria
1. Male or female aged 6-45 years*

-*Current Institutional Review Board (IRB)-approved age eligibility criteria is restricted to subjects 6 to 17 years of age at time of study enrollment
2. Diagnosis of type 1 diabetes mellitus (T1DM), using the American Diabetes Association T1DM criteria, within 100 days of study enrollment
3. Positive for at least one diabetes-related autoantibody, including but not limited to:

1. Glutamate decarboxylase (GAD-65)
2. Insulin, if obtained within 10 days of the onset of exogenous insulin therapy
3. Insulinoma antigen-2 (IA-2)
4. Zinc transporter-8 (ZnT8)
4. Peak stimulated C-peptide level = 0.2 pmol/mL following a mixed-meal tolerance test (MMTT) conducted at least 21 days from diagnosis and within 37 days of randomization (V0)
5. Signed informed consent (and informed assent of minor, if applicable).
Minimum age
6 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Severe reaction or anaphylaxis to human, humanized or murine monoclonal antibodies
2. History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease, or significant dyslipidemia
3. Any history of recent serious bacterial, viral, fungal, or other opportunistic infections
4. Have serologic evidence of current or past HIV (Human immunodeficiency virus), Hepatitis B, or Hepatitis C
5. Positive QuantiFERON Tuberculosis (TB) test, history of TB, or active TB infection
6. Active infection with Epstein-Barr virus (EBV) as defined by EBV viral load =10,000 copies per mL of whole blood
7. Active infection with Cytomegalovirus (CMV) as defined by CMV viral load =10,000 copies per mL of whole blood
8. Diagnosis of liver disease or elevated hepatic enzymes, as defined by Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), or both > 1.5 x the upper limit of age-determined normal (ULN) or total bilirubin > ULN
9. Current or prior treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status
10. Current or prior (within last 30 days) use of drugs other than insulin to treat hyperglycemia (e.g. metformin, sulfonylureas, glinides, thiazolidinediones, exenatide, liraglutide, Dipeptidyl peptidase-4 Intravenous (DPP-IV) inhibitors, or amylin)
11. Current use of any medication known to significantly influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, niacin)
12. Any of the following hematologic abnormalities, confirmed by repeat tests:

1. White blood count <3,000/microL or >14,000/microL
2. Lymphocyte count <500/microL
3. Platelet count <150,000 /microL
4. Hemoglobin <8.5 g/dL
5. . Neutrophil count <2,000 cells/microL.
13. Females who are pregnant, lactating, or planning on pregnancy during the 2- year study period
14. History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease
15. History of alcohol, drug or chemical abuse within 1 year prior to study eligibility screening evaluation
16. Any medical or psychological condition that in the opinion of the principal investigator would interfere with safe completion of the trial
17. Prior participation in a clinical trial that could increase risks associated with this clinical trial
18. Receipt of live vaccine (e.g. varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette-Guérin, and small pox) in the 6 weeks before randomization
19. High lipid levels (fasting Low-density lipoprotein (LDL) cholesterol =160 mg/dL)
20. History of significant allergy (e.g. anaphylaxis) to milk or soy proteins.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/03/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2020
Sample size
Target
Accrual to date
Final
136
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead: Kids Research Institute - Westmead
Recruitment hospital [2] 0 0
Lady Cilento Children's Hospital: Department of Endocrinology - South Brisbane
Recruitment postcode(s) [1] 0 0
Westmead 2145 - Westmead
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Minnesota
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Dakota
Country [12] 0 0
United States of America
State/province [12] 0 0
Tennessee
Country [13] 0 0
United States of America
State/province [13] 0 0
Texas
Country [14] 0 0
United States of America
State/province [14] 0 0
Washington

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Immune Tolerance Network (ITN)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
PPD
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Commercial sector/industry
Name [3] 0 0
Rho Federal Systems Division, Inc.
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Carla Greenbaum
Address 0 0
Benaroya Research Institute at Virginia Mason: Diabetes Research Program
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
When will data be available (start and end dates)?
On average, within 24 months after database lock for the trial.
Available to whom?
Open access.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.immport.org/home


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02293837