Sofosbuvir + Ribavirin Effective in Teens With HCV GT 2/3

The study included patients aged 12–17 years
The study included patients aged 12–17 years

BOSTON, MA—For adolescents with chronic hepatitis C virus (HCV) infection, treatment with sofosbuvir (SOF) and ribavirin (RBV) led to a 98% SVR12 rate with no virologic failures, reported Kathleen B. Schwarz, MD, a professor of pediatrics at Johns Hopkins University School of Medicine, Baltimore, MD, at The Liver Meeting® 2016.

The use of HCV-specific direct-acting antivirals “have transformed the treatment of adults with chronic HCV,” noted Dr. Schwarz and colleagues. However, “the standard of care for adolescents and younger children is still limited to pegylated interferon plus RBV for 24–48 weeks."

The estimated prevalence of HCV infection in children is up to 0.4% in the United States and Europe and up to 6% in resource-limited countries, or 11 million infections worldwide, they noted.

The investigators conducted an open-label study to evaluate the safety and efficacy of the all-oral regimen in HCV-infected GT2 (n=13) or GT3 (n=37) adolescents aged 12–17 years.

The patients received SOF 400mg once daily + RBV 15mg/kg daily (max 1400mg daily in 2 divided doses) for 12 weeks (GT2) or 24 weeks (GT3). The primary safety endpoint was adverse events leading to study drug discontinuation, and the key efficacy endpoint was SVR12.

In the HCV GT2 arm, 62% of the patients were male, 85% were white, mean age was 15 years, mean biomass index (BMI) was 21kg/m2 (range 16–28), mean baseline HVC RNA log10 IU/mL was 5.9, and all were treatment-naïve. In the HCV GT3 arm, 57% of patients were male, 92% were white, mean age was 15 years, mean BMI was 23kg/m2 (range 16–32), mean baseline HVC RNA log10 IU/mL was 6.2, and 76% were treatment-naïve.

Pharmacokinetic analyses showed that concentrations of SOF and its primary metabolite, GS-331007, were within the range of adult exposure seen in the Phase 2/3 studies.

Among all adolescents, SVR12 was 98% (49 of 50 patients). For those who were GT2, all 13 patients (100%) achieved SVR12, as did 36 of 37 (97%; one patient was lost to follow-up) who were GT3.

NS5B nucleos(t)ide inhibitor resistance-associated substitution F289L was detected  In 1 patient with HCV GT 3a who achieved SVR12.

The SOF + RBV regimen was well tolerated, Dr. Schwarz reported, with no serious adverse events or treatment discontinuations. In the GT2 arm, the most common adverse events were headache (3 patients; 23%), nausea (3; 23%), upper abdominal pain (2; 15%), and diarrhea (2; 15%) and, in the GT3 arm, headache (9 patients; 24%), nausea (9 patients; 24%), asthenia (5 patients; 14%), and dizziness (4 patients; 11%).

The study is ongoing in children aged 3–11 years.

“SOF + RBV represents an important treatment option for adolescents with chronic HCV GT2 or GT3 infection,” the study concluded.

The study was funded by Gilead Sciences, Inc.

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