EPIC-Peds: A Study to Learn About the Study Medicine Called PF-07321332 (Nirmatrelvir)/Ritonavir in Patients Under 18 Years of Age With COVID-19 That Are Not Hospitalized But Are at Risk for Severe Disease

Study Overview
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Brief Summary
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The purpose of this clinical trial is to learn about the safety, pharmacokinetics (pharmacokinetics helps us understand how the drug is changed and eliminated from your body after you take it), and efficacy (how well a study treatment works in the study) of the study medicine (called nirmatrelvir/ritonavir) for potential treatment of coronavirus disease 2019 (COVID-19). The study medicine will be given to patients under 18 years of age with COVID-19 that are not hospitalized but are at risk for severe disease.

Official Title
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A PHASE 2/3, INTERVENTIONAL SAFETY, PHARMACOKINETICS, AND EFFICACY, OPEN-LABEL, MULTI-CENTER, SINGLE-ARM STUDY TO INVESTIGATE ORALLY ADMINISTERED PF-07321332 (NIRMATRELVIR)/RITONAVIR IN NONHOSPITALIZED SYMPTOMATIC PEDIATRIC PARTICIPANTS WITH COVID-19 WHO ARE AT RISK OF PROGRESSION TO SEVERE DISEASE

Conditions
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COVID-19

Intervention / Treatment
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* Drug: nirmatrelvir
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male and female, age 0 to < 18 years, able to swallow for some participants Confirmed SARS-CoV-2 infection within 72 hours prior to enrollment Initial onset of COVID-19 signs/symptoms within 5 days prior to the day of enrollment and at least 1 of the specified COVID-19 signs/symptoms present at enrollment Has at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19 Exclusion Criteria: History of or need for hospitalization for the medical treatment of COVID-19 Total bilirubin >=2X upper limit of normal (ULN) (except for Gilbert's syndrome) Receiving dialysis or have known moderate to severe renal impairment Suspected or confirmed concurrent active systemic infection other than COVID-19 History of hypersensitivity or other contraindication to any of the components of the study intervention Current or expected use of any medications or substances that are highly dependent on CYP3A4 for clearance or strong inducers of cytochrome P450 (CYP)3A4 Has received or is expected to receive antibody treatment, antiviral treatment or convalescent COVID-19 plasma Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 through the study follow up Females who are pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 nirmatrelvir/ritonavir<br>nirmatrelvir/ritonavir will be given by tablets or powder by mouth twice a day for 5 days (10 doses total). Weight ≥40 kg ≥12 to <18 years ≥6 to <12 years | Drug: nirmatrelvir<br>* PF-07321332<br>Drug: ritonavir<br>* ritonavir<br>|
| Experimental: Cohort 2 nirmatrelvir/ritonavir<br>nirmatrelvir/ritonavir will be given as powder by mouth twice a day for 5 days (10 doses total) Weight ≥20 to <40 kg, ≥6 to <18 years | Drug: nirmatrelvir<br>* PF-07321332<br>Drug: ritonavir<br>* ritonavir<br>|
| Experimental: Cohort 3 nirmatrelvir/ritonavir<br>nirmatrelvir/ritonavir ≥2 to <6 years | Drug: nirmatrelvir<br>* PF-07321332<br>Drug: ritonavir<br>* ritonavir<br>|
| Experimental: Cohort 4 nirmatrelvir/ritonavir<br>nirmatrelvir/ritonavir ≥1 month (≥28 days) to <2 years | Drug: nirmatrelvir<br>* PF-07321332<br>Drug: ritonavir<br>* ritonavir<br>|
| Experimental: Cohort 5 nirmatrelvir/ritonavir<br>nirmatrelvir/ritonavir <1 month (<28 days) old | Drug: nirmatrelvir<br>* PF-07321332<br>Drug: ritonavir<br>* ritonavir<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1-2: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir | Pharmacokinetic (PK) sample(s) for Cohorts 1-2 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (10 to 13 total PK samples for Cohort 1 and 10 samples for Cohort 2). Day 1: 1 hour-post dose by Tasso device and venous blood Day 4: pre-dose (Tasso) Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post AM dose (Tasso); for Cohort 1 pre-dose, and 1, 2 hours post AM dose venous samples in approximately 10 participants. | Day 1: 1 hour-post dose; Day 4: pre-dose; Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post dose | 
| Cohort 1-2: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir | Pharmacokinetic (PK) sample(s) for Cohorts 1-2 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (10 to 13 total PK samples for Cohort 1 and 10 samples for Cohort 2). Day 1: 1 hour-post dose by Tasso device and venous blood Day 4: pre-dose (Tasso) Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post AM dose (Tasso); for Cohort 1 pre-dose, and 1, 2 hours post AM dose venous samples in approximately 10 participants. | Day 1: 1 hour-post dose; Day 4: pre-dose; Day 5: pre-dose, and 1, 2, 4, 6, 8 and 10 hours post dose | 
| Cohort 3: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir | PK sample(s) Cohort 3 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (7 total samples) Day 1: 1 hour-post dose Tasso and venous blood. Day 2: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 3: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 4: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 5: PK pre-dose and post-dose between 1 to 3 hours (Tasso) | Day 1: 1 hour-post dose; Day 2: 2-8 hours post dose; Day 3: 2-8 hours post dose; Day 4: 2-8 hours post dose; Day 5: PK pre-dose and post-dose 1 to 3 hours | 
| Cohort 3: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir | PK sample(s) Cohort 3 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (7 total samples) Day 1: 1 hour-post dose Tasso and venous blood. Day 2: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 3: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 4: between 2-8 hours post AM dose prior to PM dose (Tasso) Day 5: PK pre-dose and post-dose between 1 to 3 hours (Tasso) | Day 1: 1 hour-post dose; Day 2: 2-8 hours post dose; Day 3: 2-8 hours post dose; Day 4: 2-8 hours post dose; Day 5: PK pre-dose and post-dose 1 to 3 hours | 
| Cohort 4-5: Maximum Observed Plasma Concentration (Cmax) of nirmatrelvir and ritonavir | PK sample(s) Cohorts 4-5 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (4 total samples) Day 1: 1 hour-post dose Tasso and 1 venous blood. Day 5: PK pre-dose and post-dose AM between 3 to 5 hours (Tasso) | Day 1: 1 hour-post dose; Day 5: PK pre-dose and post-dose AM between 1 to 3 hours | 
| Cohort 4-5: Area Under the Curve to the End of the Dosing Period (AUC0-tau) of nirmatrelvir and ritonavir | PK sample(s) Cohorts 4-5 will be collected by Tasso micro-sampling device and venous blood sample at the following timepoints: (4 total samples) Day 1: 1 hour-post dose Tasso and 1 venous blood. Day 5: PK pre-dose and post-dose AM between 3 to 5 hours (Tasso) | Day 1: 1 hour-post dose; Day 5: PK pre-dose and post-dose AM between 1 to 3 hours | 
| Incidence of Treatment Emergent Adverse Events (TEAEs) leading to discontinuations. |  | From Baseline up through Day 34 | 
| Incidence of Serious Adverse Events (SAEs) leading to discontinuations. |  | From Baseline up through Day 34 | 
| Incidence of Adverse Events (AEs) leading to discontinuations. |  | From Baseline up through Day 34 | 
| Number of participants with change from Baseline in Vital Signs |  | From Baseline up through Day 34 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Viral load assessment titers measured via reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal or nasal swabs over time | To evaluate the change in viral loads in pediatric participants from birth to <18 years of age with COVID-19 who are at risk of progression to severe disease. | Baseline, Day 4, 5, 6, 10, 14 and 28 | 
| Proportion of participants with COVID-19 related hospitalization or death from any cause | To evaluate the efficacy of nirmatrelvir/ritonavir for the treatment of COVID-19 in nonhospitalized symptomatic pediatric participants with COVID-19 who are at increased risk of progression to severe disease. | From Baseline through Day 28 | 
| Patient assessment on acceptability and palatability of nirmatrelvir/ritonavir (film-coated tablets and oral powder) | Frequency of responses to visual questionnaire on taste. | At baseline only for tablets and after each dose for powder formulation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), Pediatrics