Nirmatrelvir/Ritonavir for COVID-19 in Children

Recruiting at 118 trial locations

Overseen By Pfizer CT.gov Call Center

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: CYP3A4 drugs, Antivirals

Disqualifiers: Renal impairment, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 15

Duration: 1 week

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safety and effectiveness of the combination of nirmatrelvir and ritonavir (known as Paxlovid) for treating COVID-19 in children. It focuses on those under 18 who have COVID-19, are not hospitalized, and have a higher risk of severe illness. Participants must have tested positive for COVID-19 within the last three days and show symptoms like fever or cough. Different groups in the trial will receive the medicine either as tablets or powder. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for COVID-19 in children.

Will I have to stop taking my current medications?

The trial requires that participants do not use medications that are highly dependent on CYP3A4 for clearance or strong inducers of cytochrome P450 (CYP)3A4. If you are taking such medications, you may need to stop them to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown limited information about the safety of nirmatrelvir/ritonavir (Paxlovid) in children, particularly those under 12 years old or weighing less than 88 pounds. The treatment is under study for young people with COVID-19, but its safety for this age group remains under investigation. Previous studies found that it can reduce the risk of hospitalization in children with COVID-19 who are not already hospitalized. Doctors should carefully weigh the benefits and risks before prescribing it to children. While the treatment appears promising, its safety in children continues to be closely monitored and studied. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for COVID-19?

Researchers are excited about Nirmatrelvir and Ritonavir for treating COVID-19 in children because they offer a targeted approach that differs from most existing treatments. While many COVID-19 treatments focus on alleviating symptoms or supporting immune function, Nirmatrelvir is a protease inhibitor that directly targets the virus's ability to replicate. This mechanism of action can potentially limit the progression of the infection more efficiently. Additionally, the treatment's oral administration, available as both tablets and powder, makes it easier for children across various age groups, including infants, to receive the medication. This ease of use and targeted viral inhibition set it apart from current options like monoclonal antibodies or supportive care treatments.

What evidence suggests that nirmatrelvir/ritonavir might be an effective treatment for COVID-19 in children?

Research shows that the medication combination nirmatrelvir/ritonavir, known as Paxlovid, can reduce the risk of hospitalization in children with COVID-19 who are at risk of severe illness but not currently hospitalized. This trial will evaluate nirmatrelvir/ritonavir in various age groups, including teenagers aged 12 to 18, where studies have found it helps prevent serious COVID-19 symptoms. Additionally, evidence suggests that nirmatrelvir/ritonavir could be a safe and effective treatment for severe COVID-19 in children. For children aged 6 to 14, this treatment has proven practical, safe, and effective. Paxlovid has shown promise in managing COVID-19 symptoms in younger age groups, and this trial will further assess its effectiveness across different pediatric cohorts. ^{3 6 7 8 9}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for children and teenagers under 18 who can swallow pills, have tested positive for COVID-19 within the last 72 hours, are at risk of severe illness but not hospitalized. They must show symptoms within 5 days before joining. Those with certain treatments or conditions like severe kidney issues, other infections, or using specific drugs that affect the body's drug processing system cannot join.

Inclusion Criteria

You have tested positive for COVID-19 within the last 3 days before joining the study.

You started showing signs of COVID-19 within 5 days before joining the study, and you still have at least one of the specific COVID-19 signs.

You have a medical condition that makes you more likely to get very sick from COVID-19.

Exclusion Criteria

You have received or are going to receive specific treatments for COVID-19.

You have a serious infection other than COVID-19.

History of hypersensitivity or other contraindication to any of the components of the study intervention

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive nirmatrelvir/ritonavir orally twice a day for 5 days

1 week

Daily visits for 5 days

Pharmacokinetics Monitoring

PK samples collected to assess drug concentration and pharmacokinetics

5 days

Multiple visits for blood sampling

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Visits on Day 10, 14, and 28

What Are the Treatments Tested in This Trial?

Interventions

• Nirmatrelvir
• Ritonavir

Trial Overview

The study tests PF-07321332 (Nirmatrelvir)/Ritonavir in young patients to see how safe it is and how well it works against COVID-19. It looks at how their bodies handle the medication and its effectiveness in preventing serious disease.

How Is the Trial Designed?

Group I: Cohort 5 nirmatrelvir/ritonavir Experimental Treatment 2 Interventions

nirmatrelvir/ritonavir \<1 month (\<28 days) old

Group II: Cohort 4 nirmatrelvir/ritonavir Experimental Treatment 2 Interventions

nirmatrelvir/ritonavir ≥1 month (≥28 days) to \<2 years

Group III: Cohort 3 nirmatrelvir/ritonavir Experimental Treatment 2 Interventions

nirmatrelvir/ritonavir ≥2 to \<6 years

Group IV: Cohort 2 nirmatrelvir/ritonavir Experimental Treatment 2 Interventions

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

Group V: Cohort 1 nirmatrelvir/ritonavir Experimental Treatment 2 Interventions

nirmatrelvir/ritonavir will be given by tablets or powder by mouth twice a day for 5 days (10 doses total). Weight ≥40 kg 1. ≥12 to \<18 years 2. ≥6 to \<12 years

Nirmatrelvir is already approved in United States, European Union for the following indications:

Approved in United States as Paxlovid for:

• Treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death

Approved in European Union as Paxlovid for:

• Treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

A 14-day treatment with nitazoxanide successfully resolved intractable norovirus gastroenteritis in a 13-year-old kidney transplant recipient, demonstrating its potential efficacy even under high levels of immunosuppression.

Nitazoxanide cleared norovirus from the patient's stool, suggesting it could be a viable treatment option for pediatric transplant patients when other therapies fail and reducing immunosuppression is not possible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of chronic norovirus gastroenteritis with nitazoxanide in a pediatric kidney transplant recipient. Haubrich, K., Gantt, S., Blydt-Hansen, T.[2021]

Combination therapy with peginterferon-α and ribavirin has been approved for treating chronic Hepatitis C in children over 3 years old, based on positive results from multicenter studies.

The treatment is derived from adult trials, showing it is more effective than standard interferon-α and ribavirin, although the long-term outcomes and safety in children still require further evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic hepatitis C virus infection in children and adolescents: Epidemiology, natural history, and assessment of the safety and efficacy of combination therapy. Indolfi, G., Bartolini, E., Casavola, D., et al.[2021]

Nirmatrelvir-ritonavir (Paxlovid) has been authorized for emergency use to treat COVID-19, but it is associated with various skin-related side effects that need to be monitored.

There are significant drug-to-drug interactions between Paxlovid and commonly used dermatological medications, which could complicate treatment plans for patients with skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir-ritonivir, COVID-19, and possible adverse cutaneous reactions. Albrecht, JM., Cooper, BR., Waller, JD., et al.[2023]

Nirmatrelvir-ritonavir (Paxlovid®) is an oral treatment for Covid-19 that has been available since February 4, 2022.

It is specifically designed for individuals at very high risk of developing severe forms of the disease, highlighting its targeted use for vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nirmatrelvir/ritonavir (Paxlovid®), a treatment for Covid-19]. Buxeraud, J., Faure, S., Fougere, É.[2022]

Chronic hepatitis C infection in children can lead to serious health issues, but treatment strategies have improved, with sustained virologic response rates of about 36% for conventional interferon and 50% for interferon combined with ribavirin.

Pegylated interferon treatments show promise in adults, but their effectiveness in children is less understood; however, factors like HCV genotype and low pretreatment viral levels are linked to better treatment outcomes, despite potential side effects like flu-like symptoms and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of chronic hepatitis C in children. González-Peralta, RP.[2018]

Paxlovid, which combines nirmatrelvir and ritonavir, is an effective oral antiviral treatment for COVID-19, with nirmatrelvir specifically targeting the SARS-CoV-2 main protease to inhibit viral replication.

Ritonavir enhances the effectiveness of nirmatrelvir by slowing its metabolism, but it also poses a risk for drug interactions due to its role as a CYP3A4 inhibitor, necessitating careful management of other medications during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences. Azanza, JR., Mensa, J., González Del Castillo, J., et al.[2022]

Nirmatrelvir plus ritonavir (Paxlovid™) is an effective treatment for COVID-19, specifically designed for adults at high risk of severe disease who do not need supplemental oxygen, receiving its first authorization in December 2021 in the UK.

The combination works by inhibiting the SARS-CoV-2 main protease (nirmatrelvir) and includes ritonavir to enhance its effectiveness, with emergency use authorization granted in the USA and EU for similar indications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nirmatrelvir Plus Ritonavir: First Approval. Lamb, YN.[2022]

Out of over 1.4 million pediatric patients, only 920 received a prescription for nirmatrelvir/ritonavir (Paxlovid), indicating that it is prescribed infrequently to children, particularly those with chronic health conditions.

A significant portion of patients (53%) who were prescribed nirmatrelvir/ritonavir had no documented COVID-19 infection in their electronic health records, suggesting a need for improved prescribing practices to ensure appropriate use of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic. Bose-Brill, S., Hirabayashi, K., Pajor, NM., et al.[2023]

In a retrospective analysis of 3 mild COVID-19 cases in children treated with Paxlovid, all patients became symptom-free within 1-2 days and tested negative for SARS-CoV-2 within 2-4 days after starting treatment.

Paxlovid was found to be effective and relatively safe, with no significant adverse effects reported, except for one case of mild skin rash that resolved after stopping the medication, and all patients maintained normal liver and kidney function during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[COVID-19 treated with oral Nirmatrelvir-Ritonavir in 3 children]. Shi, S., Dong, N., Ding, Y., et al.[2022]

In a pediatric oncology unit, four children with acute lymphoblastic leukemia experienced severe norovirus infections, leading to chronic viral shedding and complications such as persistent diarrhea and malabsorption.

Among the patients, two did not respond to the antiviral treatment nitazoxanide and unfortunately did not survive, while one child who received both nitazoxanide and favipiravir is currently doing well and continuing chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Norovirus Infection in Children with Acute Lymphoblastic Leukemia. Reddy, NA., Raj, K., Lashkari, HP.[2023]

The standard treatment for pediatric chronic hepatitis C in children aged 3 years and older is pegylated interferon (IFN) α-2a or 2b combined with ribavirin, which was initially developed for adults.

New direct-acting antiviral agents (DAAs) are being developed to target different stages of the hepatitis C virus lifecycle, and future drug regimens specifically designed for children are expected to prioritize high potency, resistance barriers, and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New treatments for chronic hepatitis C: an overview for paediatricians. Serranti, D., Indolfi, G., Resti, M.[2018]

A case report of a 14-year-old kidney transplant patient showed that using nirmatrelvir/ritonavir for COVID-19 led to dangerously high levels of tacrolimus, an immunosuppressant, indicating a significant drug interaction.

After stopping nirmatrelvir/ritonavir, the patient's tacrolimus levels and kidney function returned to normal, highlighting the need for caution when prescribing this COVID-19 treatment to pediatric patients on tacrolimus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elevated tacrolimus levels after treatment with nirmatrelvir/ritonavir (Paxlovid) for COVID-19 infection in a child with a kidney transplant. Young, C., Papiro, T., Greenberg, JH.[2023]

The study developed a physiologically-based pharmacokinetic (PBPK) model for PAXLOVID™, which combines nirmatrelvir and ritonavir, showing that the model accurately predicts the drug's pharmacokinetics in humans, with results within 20% of observed values.

This PBPK model can be used to understand how nirmatrelvir behaves in different populations and to assess drug-drug interactions, highlighting its importance in the development of effective treatments for diseases like COVID-19.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics. Sagawa, K., Lin, J., Jaini, R., et al.[2023]

Citations

1.

nature.com

nature.com/articles/s41467-024-49235-8

Effectiveness of nirmatrelvir/ritonavir in children and ...

The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with ...

2.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38851796/

Effectiveness of nirmatrelvir/ritonavir in children and ...

The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39951139/

Evolving COVID-19 Landscape: Assessing the ...

This study evaluates nirmatrelvir/ritonavir (Paxlovid) in preventing severe coronavirus disease 2019 in adolescents (12-18).

4.

bmcpediatr.biomedcentral.com

bmcpediatr.biomedcentral.com/articles/10.1186/s12887-025-05807-1

Paxlovid for the treatment of severe or critical COVID-19 in ...

Our findings suggest that Paxlovid may be a safe and effective option for treating severe or critical COVID-19 in children.

5.

journals.lww.com

journals.lww.com/md-cases/fulltext/2025/02000/sars_cov_2_treated_with_oral.2.aspx

SARS-COV-2 treated with oral nirmatrelvir–ritonavir in...

This study aimed to analyze the feasibility, safety, and efficacy of nirmatrelvir ritonavir in the treatment of 6 to 14 year old children with severe acute ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39774678/

Safety of Nirmatrelvir-Ritonavir Administration in Children ...

This study reports the clinical outcomes of pediatric patients treated with nirmatrelvir and ritonavir (N/R) for SARS-CoV-2 infection.

7.

chop.edu

chop.edu/clinical-pathway/covid-disease-nirmatrelvir-ritonavir-paxlovid

Nirmatrelvir-ritonavir (Paxlovid) — Clinical Pathway: All ...

Providers should carefully consider the risk/benefit ratio of Paxlovid before prescribing, noting that there are no pediatric safety or efficacy data for this ...

8.

fda.gov

fda.gov/media/155051/download

fact sheet for patients, parents, and caregivers emerg

There is limited information about the safety and effectiveness of using PAXLOVID to treat children younger than 12 years of age or weighing less than 88 pounds ...

9.

publications.aap.org

publications.aap.org/hospitalpediatrics/article/14/8/e341/198033/Pediatric-Nirmatrelvir-Ritonavir-Prescribing

Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During ...

Although nirmatrelvir/ritonavir has a potential role in mitigating COVID-19 disease burden among children,6,11 data on pediatric use, safety, ...