Phase 2
N=67
Imatinib Treatment in Recent Onset Type 1 Diabetes Mellitus
Diabetes Mellitus, Type I · Diabetes Mellitus, Insulin-Dependent, 1 · Type 1 Diabetes Mellitus · Insulin-Dependent Diabetes Mellitus 1 · IDDM
Bottom Line
View on ClinicalTrials.gov: NCT01781975 ↗Enrolled (actual)
67
Serious AEs
16.4%
Results posted
Aug 2018
Primary outcome: Primary: 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 — 0.834; 0.775 nmol/L — p=0.048
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Imatinib Mesylate (Drug); Placebo (For imatinib mesylate) (Drug)
- Age
- Adult · 18+ yrs
- Sex
- All
- Sponsor
- University of California, San Francisco
- Primary completion
- May 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
0.834; 0.775 | 0.048 sig |
| SECONDARY Area Under the Stimulated C-peptide Curve (AUC) Mean Over 4 Hours at 24 Months |
0.472; 0.389 | — |
| SECONDARY Change in HbA1c Levels Over Time |
6.33; 6.51; 6.44; 7.03 | — |
| SECONDARY Change in Insulin Dose (Units/kg) Over Time |
0.307; 0.413; 0.389; 0.488 | — |
| SECONDARY Number of Severe Hypoglycemic Events |
2; 3 | — |
| SECONDARY Number of Adverse Events |
172; 28 | — |
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.
Eligibility Criteria
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.
Exclusion Criteria
- Prior history of any significant cardiac disease such as congestive heart failure, myocardial infarction, arrhythmia, or structural defects or suspicion thereof.
- Leukopenia ( 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.
Data sourced from ClinicalTrials.gov (NCT01781975). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.