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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01781975




Registration number
NCT01781975
Ethics application status
Date submitted
17/01/2013
Date registered
1/02/2013
Date last updated
11/02/2020

Titles & IDs
Public title
Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus
Scientific title
Safety and Efficacy of Imatinib for Preserving Beta-Cell Function in New-Onset Type 1 Diabetes Mellitus
Secondary ID [1] 0 0
17-2013-6
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diabetes Mellitus, Type I 0 0
Diabetes Mellitus, Insulin-Dependent, 1 0 0
Type 1 Diabetes Mellitus 0 0
Insulin-Dependent Diabetes Mellitus 1 0 0
IDDM 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 - Imatinib Mesylate
Treatment: Drugs - Placebo (For imatinib mesylate)

Experimental: Imatinib Mesylate - 400 mg imatinib given once daily basis.

Placebo Comparator: Placebo - Placebo given once daily basis.


Treatment: Drugs: Imatinib Mesylate


Treatment: Drugs: Placebo (For imatinib mesylate)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Area Under the Stimulated C-peptide Curve (AUC) Mean Over the First 2 Hours of a 4 Hour Mixed Meal Tolerance Test at the 1 Year Visit
Timepoint [1] 0 0
Visit 9 (Week 52) at 0, 15, 30, 60, 90, 120 minutes post-dose
Secondary outcome [1] 0 0
Area Under the Stimulated C-peptide Curve (AUC) Mean Over 4 Hours at 24 Months
Timepoint [1] 0 0
Visit 13 (Week 104)
Secondary outcome [2] 0 0
Change in HbA1c Levels Over Time
Timepoint [2] 0 0
Visit 9 (Week 52) and Visit 13 (Week 104)
Secondary outcome [3] 0 0
Change in Insulin Dose (Units/kg) Over Time
Timepoint [3] 0 0
Visit 9 (Week 52) and Visit 13 (Week 104)
Secondary outcome [4] 0 0
Number of Severe Hypoglycemic Events
Timepoint [4] 0 0
Visit 0 (Week 0), Visit 9 (Week 52), and Visit 13 (Week 104)
Secondary outcome [5] 0 0
Number of Adverse Events
Timepoint [5] 0 0
Adverse Events will be assessed at Visit 0 (week 0), Visit 1 (Week 2), Visit 2 (Week 4), and every month thereafter.

Eligibility
Key inclusion criteria
- Males and females age 12-45 years of age who meet the ADA standard T1DM criteria1.
Positive for at least one islet cell autoantibody. Initial enrollment will be for
subjects ages 18-45, with the goal to lower the age down to 12 upon acceptable safety
review and prospect of benefit for this initial older cohort.

- Diagnosis of T1DM within 100 days of Visit 0.

- Peak stimulated C-peptide level >0.2 pmol/mL following an MMTT.

- Participants of childbearing age who are sexually active must agree to use an
effective form of birth control (e.g., barrier method, oral contraception, or
surgery). For females, these contraceptive measures must be maintained throughout the
study; for males these measures must be followed for a minimum of 3 months after
discontinuation of imatinib therapy.
Minimum age
18 Years
Maximum age
45 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Prior history of any significant cardiac disease such as congestive heart failure,
myocardial infarction, arrhythmia, or structural defects or suspicion thereof.

- Leukopenia (<3,000 leukocytes/µL), neutropenia (<1,500 neutrophils/µL), or
thrombocytopenia (<125,000 platelets/µL).

- Low Hemoglobin (baseline hemoglobin below lower limit of normal)

- Prior history of anaphylaxis, angioedema or serious cutaneous drug reactions

- Any sign of significant chronic active infection (e.g., hepatitis, tuberculosis, EBV,
CMV, or toxoplasmosis), or screening laboratory evidence consistent with a significant
chronic active infection (such as positive for HIV, PPD, or HBSAg). Significant acute
infections must be resolved before treatment may commence, e.g., acute respiratory
tract, urinary tract, or gastrointestinal tract infections.

- Anticipated ongoing use of diabetes medications other than insulin that affect glucose
homeostasis, such as metformin, sulfonylureas, thiazolidinediones, glucagon-like
peptide 1 (GLP-1) mimetics, dipeptidyl peptidase IV (DPP-IV) inhibitors, or amylin.

- Prior or current treatment that is known to cause a significant, ongoing change in the
course of T1DM or immunologic status, including high-dose inhaled, extensive topical
or systemic glucocorticoids.

- Evidence of liver dysfunction, with alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) >2.0 times the upper limit of normal persistent for 1 week or
greater.

- Evidence of renal insufficiency as indicated by serum creatinine > 1.2 times the upper
limit of normal and confirmed in a repeat test at least one week apart. Evidence of
clinically significant metabolic bone disease (except adequately treated rickets).

- Females who are pregnant at the time of screening or unwilling to defer pregnancy
during the 24-month study period.

- Prior treatment with imatinib or related tyrosine kinase inhibitor.

- Unable to avoid medications that affect CYP3A4: either inducers that may decrease
imatinib levels, or inhibitors that may increase drug concentrations. (Refer to
section 1.5.1.12 for a complete list of inducers and inhibitors.)

- Height standard deviation score =2 standard deviations below mean

- Any sign of QT prolongation on Visit -1 noted on ECG (> 450 ms in males and > 470 ms
in females)

- Known coagulation disorders or use of anticoagulants

- Current and anticipated on-going treatment with drugs that may increase or decrease
imatinib plasma concentrations (CYP3A4 family inhibitors or inducers) or drugs that
may have their plasma concentration altered by imatinib (drugs metabolized by CYP3A4/5
and CYP2D6).

- Any condition that, in the investigator's opinion, may compromise study participation
or may confound the interpretation of the study results.

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 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
1/01/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2018
Sample size
Target
Accrual to date
Final
67
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Walter and Eliza Hall Institute of Medical Research - Melbourne
Recruitment postcode(s) [1] 0 0
3050 - Melbourne
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
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
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
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Other
Name
University of California, San Francisco
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Juvenile Diabetes Research Foundation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of insulin-producing
ß cells. Although exogenous insulin is widely available, it is not possible for affected
individuals to consistently achieve euglycemia with current technology, and thus they are at
risk for devastating long-term complications. This phase II study is designed to evaluate the
safety and efficacy of imatinib mesylate as a novel therapy for new-onset T1DM. Imatinib is a
first-in-class tyrosine kinase inhibitor.

This study will explore the potential role of short-term therapy with imatinib to induce
tolerance and possibly lead to a durable long-term remission of T1DM.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01781975
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stephen E Gitelman, MD
Address 0 0
University of California, San Francisco
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01781975