Pharmaceutical company Pfizer has initiated a Phase II/III study of Paxlovid (nirmatrelvir [PF-07321332] tablets and ritonavir tablets). The treatment reportedly is the first oral therapy specifically intended to fight COVID-19 that is being evaluated in a pediatric clinical trial.
The treatment currently is authorized under emergency use authorization (EUA) by the US Food and Drug Administration. This EUA covers high-risk patients (both adult and pediatric) who are 12 years of age or older and weigh 40 kg or more.
The study—termed EPIC-PEDS (evaluation of protease inhibition for COVID-19 in pediatric patients)—is aimed at evaluating the safety, pharmacokinetics, and efficacy of Pfizer’s Paxlovid therapy in non-hospitalized, symptomatic, pediatric participants with a confirmed diagnosis of COVID-19, whom medical professionals have determined are at risk of progression to severe disease.
Mikael Dolsten (chief scientific officer and president of worldwide research, development, and medical for Pfizer), said, “Since the beginning of the pandemic, more than 11 million children under the age of 18 in the US alone have tested positive for COVID-19, representing nearly 18% of reported cases and leading to more than 100,000 hospital admissions. There is a significant unmet need for outpatient treatments that can be taken by children and adolescents to help prevent progression to severe illness, including hospitalization or death."
“Paxlovid is already authorized or approved in many countries around the world, with more than 1.5m treatment courses delivered thus far and 30m expected by July to help combat this devastating disease,” Dolsten added. “We are proud to expand studies of our novel COVID-19 treatment to include pediatric participants to further evaluate the safety and efficacy of this treatment in this important population.”
According to Pfizer, the Phase II/III trial is an open-label, multi-center, single-arm study in approximately 140 pediatric participants under 18 years old. Initial enrollment features two cohorts:
- Cohort 1: participants aged 6 to 17 weighing at least 40 kg
- Cohort 2: patients aged 6 to 17 that weigh between 20 kg and 40 kg
Pfizer reports that participants enrolled in the first cohort will receive Paxlovid (nirmatrelvir/ritonavir 300 mg/100 mg) orally twice daily for five days, which is the currently authorized dosing for pediatric patients 12 years of age and older weighing at least 40kg. The participants in the second cohort will receive PAXLOVID (nirmatrelvir/ritonavir 150 mg/100 mg) orally twice daily for five days.
Pfizer also is working on the development of an age-appropriate formulation for three additional planned cohorts younger than 6 years old. The company reports it plans to enroll the trial to include these younger age groups as data from Cohorts 1 and 2 and the new formulation are available; an independent data monitoring committee (DMC) will review the safety data of participants in each cohort.
Data from the Phase II/III study of non-hospitalized, high-risk adults with COVID-19 reportedly showed Paxlovid reduced risk of hospitalization or death by 89% (within three days of symptom onset) and 88% (within five days of symptom onset) from any cause compared to placebo, with no deaths observed in the treatment group. Treatment-emergent adverse events were comparable between PAXLOVID (23%) and placebo (24%), most of which were mild in intensity.
To date, the safety and effectiveness of Paxlovid have not yet been directly established in pediatric patients. Although other clinical trials evaluating the treatment did not include participants under the age of 18, the FDA authorized it for emergency use in pediatric patients 12 years of age and older weighing at least 40 kg, as pharmacokinetic-pharmacodynamic (PK/PD) modeling determined that the authorized adult dosing regimen would result in comparable blood concentration levels of the drug in this population and the adults with similar body weight who were included in the EPIC-HR trial.
Paxlovid currently is authorized or approved in more than 50 countries.