Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial
The Lancet - Early Online Publication, 06/29/2011
Sherry N et al. - Findings of exploratory analyses suggest that future studies of immunotherapeutic intervention with teplizumab might have increased success in prevention of a decline in Β-cell function (measured by C-peptide) and provision of glycaemic control at reduced doses of insulin if they target patients early after diagnosis of diabetes and children.Methods
- In this 2-year trial, patients aged 8—35 years who had been diagnosed with type 1 diabetes for 12 weeks or fewer were enrolled and treated at 83 clinical centres in North America, Europe, Israel, and India.
- Participants were allocated (2:1:1:1 ratio) by an interactive telephone system, according to computer-generated block randomisation, to receive one of three regimens of teplizumab infusions (14-day full dose, 14-day low dose, or 6-day full dose) or placebo at baseline and at 26 weeks.
- The Protégé study is still underway, and patients and study staff remain masked through to study closure.
- The primary composite outcome was the percentage of patients with insulin use of less than 0•5 U/kg per day and glycated haemoglobin A1c (HbA1C) of less than 6•5% at 1 year.
- Analyses included all patients who received at least one dose of study drug.
- 763 patients were screened, of whom 516 were randomised to receive 14-day full-dose teplizumab (n=209), 14-day low-dose teplizumab (n=102), 6-day full-dose teplizumab (n=106), or placebo (n=99).
- Two patients in the 14-day full-dose group and one patient in the placebo group did not start treatment, so 513 patients were eligible for efficacy analyses.
- The primary outcome did not differ between groups at 1 year: 19•8% (41/207) in the 14-day full-dose group; 13•7% (14/102) in the 14-day low-dose group; 20•8% (22/106) in the 6-day full-dose group; and 20•4% (20/98) in the placebo group.
- 5% (19/415) of patients in the teplizumab groups were not taking insulin at 1 year, compared with no patients in the placebo group at 1 year (p=0•03).
- Across the four study groups, similar proportions of patients had adverse events (414/417 [99%] in the teplizumab groups vs 98/99 [99%] in the placebo group) and serious adverse events (42/417 [10%] vs 9/99 [9%]).
- The most common clinical adverse event in the teplizumab groups was rash (220/417 [53%] vs 20/99 [20%] in the placebo group).