Hydroxychloroquine in Individuals At-risk for Type 1 Diabetes Mellitus

This study is testing a medication, called hydroxychloroquine (HCQ) to assess safety and
effectiveness to prevent individuals at risk of type 1 diabetes (T1D) from progressing to
type 1 diabetes.

HCQ is approved by the U.S. Food and Drug Administration as a treatment for malaria, lupus,
and rheumatoid arthritis. HCQ has been used extensively for treatment of autoimmune disease
in adults, children, and during pregnancy. This medication has not previously been studied as
a treatment to prevent T1D.

The goal of this study is to learn if HCQ can help prevent or delay progression from normal
glucose tolerance (Stage 1) to abnormal glucose tolerance (Stage 2) or type 1 diabetes (Stage
3).

The study involves 5 visits in the first 6 months, then 1 visit every 6 months for the
remainder of the study.

Inclusion Criteria:

1. Participant in TrialNet Pathway to Prevention Study (TN01)

2. Age 3 years or greater at the time of randomization

3. Willing to provide informed consent

4. Normal glucose tolerance by OGTT within 7 weeks (no more than 52 days) of baseline

5. Two or more diabetes-related autoantibodies present on two separate samples

6. Weight of 12 kg or greater at screening

7. If a female participant with reproductive potential, willing to avoid pregnancy and
undergo pregnancy testing prior to randomization and at each study visit

8. Anticipated ability to swallow study medication.

Exclusion Criteria:

1. Abnormal Glucose Tolerance or Diabetes

2. History of treatment with insulin or other diabetes therapies

3. Ongoing use of medications known to influence glucose tolerance

4. Ongoing or anticipated future use of medications known to have untoward interactions
with hydroxychloroquine

5. Known hypersensitivity to 4-aminoquinoline compounds

6. G6PD deficiency

7. History of retinopathy

8. Have an active infection at time of randomization

9. Have serologic evidence of current or past HIV, Hepatitis B (positive for Hepatitis B
core antibody or surface antigen), or Hepatitis C infection

10. Deemed unlikely or unable to comply with the protocol or have any complicating medical
issues, including prolonged QT interval, a disease previously or likely in the future
to require immunosuppression, or abnormal clinical laboratory results that interfere
with study conduct or cause increased risk.