Nirmatrelvir/Ritonavir for COVID-19 in Children

Recruiting at 111 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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Nirmatrelvir/Ritonavir (Paxlovid) for treating COVID-19 in children?

A study involving three children with mild COVID-19 symptoms showed that Paxlovid helped them become symptom-free within 1-2 days and test negative for the virus within 2-4 days, with no serious side effects observed. ^{1 2 3 4 5}

Is Nirmatrelvir/Ritonavir (Paxlovid) safe for children with COVID-19?

Nirmatrelvir/Ritonavir (Paxlovid) has been used in a small number of children with COVID-19, and it was found to be relatively safe. In these cases, no serious side effects were reported, although one child experienced mild skin rashes that went away after stopping the medication. ^{1 2 6 7 8}

How is the drug Nirmatrelvir/Ritonavir unique for treating COVID-19 in children?

Nirmatrelvir/Ritonavir, also known as Paxlovid, is unique because it combines two antiviral drugs that work together to block the virus from multiplying in the body, which is different from other treatments that might only target one aspect of the virus. This combination is specifically designed to treat COVID-19, whereas other treatments might be repurposed from other viral infections. ^{9 10 11 12 13}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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 are able to swallow.

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

Male and female, age 0 to < 18 years, able to swallow for some participants

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pediatric Nirmatrelvir/Ritonavir Prescribing Patterns During the COVID-19 Pandemic. [2023]

2. China pubmed.ncbi.nlm.nih.gov

[COVID-19 treated with oral Nirmatrelvir-Ritonavir in 3 children]. [2022]

3. Germany 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. [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Nirmatrelvir/ritonavir (Paxlovid®), a treatment for Covid-19]. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Physiologically-Based Pharmacokinetic Modeling of PAXLOVID™ with First-Order Absorption Kinetics. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Nirmatrelvir-ritonivir, COVID-19, and possible adverse cutaneous reactions. [2023]

7. Spain pubmed.ncbi.nlm.nih.gov

Interactions listed in the Paxlovid fact sheet, classified according to risks, pharmacological groups, and consequences. [2022]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Nirmatrelvir Plus Ritonavir: First Approval. [2022]

9. Denmark pubmed.ncbi.nlm.nih.gov

Successful treatment of chronic norovirus gastroenteritis with nitazoxanide in a pediatric kidney transplant recipient. [2021]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Norovirus Infection in Children with Acute Lymphoblastic Leukemia. [2023]

11. Denmark pubmed.ncbi.nlm.nih.gov

Treatment of chronic hepatitis C in children. [2018]

12. New Zealand 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. [2021]

13. United States pubmed.ncbi.nlm.nih.gov

New treatments for chronic hepatitis C: an overview for paediatricians. [2018]