Clinical Study Overview

The safety and efficacy of LAMPIT for the treatment of Chagas disease in pediatric patients birth to <18 years of age and weighing at least 2.5 kg were demonstrated in one prospective, randomized, double-blind trial conducted in Argentina, Bolivia and Colombia (Trial 1, NCT02625974). This trial consisted of 2 parts, Part 1 which included treatment with LAMPIT and one year post-treatment follow-up and Part 2, which included an additional three-years of follow up.

Trial 1: Treatment with LAMPIT including One Year Post-treatment Follow-up (Part 1)

Pediatric patients (n=330) with serologic evidence of T. cruzi infection and without Chagas disease-related cardiac or gastrointestinal symptoms were randomly assigned in a 2:1 fashion to a 60-day (n=219) or a 30-day (n=111) LAMPIT treatment regimen. Patients were followed up for one year. LAMPIT was administered three times a day with food using the following body weight-based dosing regimens: pediatric patients weighing less than 41 kg received a total daily dose of 10-20 mg/kg, and those weighing 41 kg or more received a total daily dose of 8-10 mg/kg [see Dosage and Administration (2.2)]. Chagas disease diagnosis was confirmed by direct observation of T. cruzi by concentration test in patients <8 months of age at randomization and by demonstrating positive results for both the lysate enzyme-linked immunosorbent assay (ELISA) and the recombinant ELISA in patients ≥8 months to <18 years of age at randomization. 

Serological response to treatment was defined as ≥20% decrease in optical density measured by lysate and recombinant ELISA in subjects >8 months to <18 years or seroconversion to negative (defined as negative immunoglobulin G concentration in all patients) at 1-year post-treatment follow-up.

The results for both the lysate ELISA and the recombinant ELISA (Table 5) showed superiority in favor of the LAMPIT 60-day arm compared to the LAMPIT 30-day arm (not an approved dosing regimen). 

Table 5: Efficacy Results using Lysate ELISA and Recombinant ELISA at 1 year Post-Treatment

The F29 ELISA detects antibodies to recombinant antigens obtained from the flagellar protein F29 of T. cruzi. Of the 214 patients who were seropositive for the assay at baseline, 46 of 142 (32.4%) in the 60-day LAMPIT treatment arm and 20 of 72 (27.8%) in the 30-day LAMPIT treatment arm (not an approved dosing regimen) seroconverted to negative at the 1-year post-treatment follow-up. Twenty of 59 (33.9%, 95% CI: 22.1%, 47.4%) patients between 6 and 12 years of age in the 60-day arm seroconverted to negative at the 1-year post-treatment follow-up. A similar seroconversion rate was observed in patients 6 and 12 years of age in the 30-day treatment arm. These rates were higher than the 2.8% conversion rate from historical data1 for untreated patients between 6 and 12 years old at 12 months using the F29 ELISA.

Trial 1: Additional Three-years of Follow-up (Part 2)

To determine the seroconversion rate in patients treated with LAMPIT at the 4-year time point, a total of 295 (197 in the 60-day regimen and 98 in the 30-day regimen) of the 330 pediatric patients were followed for another 3 years after the end of Part 1. Seroconversion to negative confirmed by three assays, lysate ELISA, recombinant ELISA and IHA, was evaluated in patients in the 60-day treatment arm by age group (Table 6) in Part 2. Patients were considered as seroconverted to negative if all three test results were negative. All seroconversions at 4 years post-treatment were from patients who were <2 years of age at baseline. Nine of 11 (81.8%) patients in the 60-day treatment arm who were <8 months of age at baseline seroconverted to negative at 4 years post-treatment. Among 39 patients in the 60-day treatment arm who were 0 to 4 years of age at baseline, 9 (23.1%) seroconverted for 2 or more consecutive years, which was higher than the 0% conversion rate from historical data2 for untreated patients infected between 0 and 4 years of age during long-term follow-up.

Table 6: Efficacy Results using Seroconversion to Negative Confirmed by Lysate ELISA, Recombinant ELISA and IHA at 4 years Post-Treatment

* A positive T. cruzi concentration test was required for subjects <8 months of age at baseline for enrollment

The efficacy of LAMPIT in pediatric patients 5 to <18 years of age was extrapolated from efficacy established in the younger pediatric population between 0 and 4 years of age. Biologically, it is expected that LAMPIT would have the same effect on T. cruzi in all pediatric age groups. The pathogenesis of Chagas disease is the same across the pediatric population; however, older patients may have a longer duration of infection than younger patients. Given longer duration of infection, time to seroconversion is expected to be longer. Based on published studies, younger pediatric patients seroconvert faster.2,3 The lack of seroconversion to negative on traditional assays in older pediatric patients in Trial 1 is not unexpected given the duration of follow up of 4 years. It is expected that seroconversion rates would increase in older pediatric age groups over time. Supportive evidence of efficacy was provided by data on seroconversion to negative by the F29 ELISA.