A Phase 2/3 Safety, Pharmacokinetics, and Efficacy Study of Nirmatrelvir/Ritonavir in Paediatric, Nonhospitalized Symptomatic Participants With COVID-19 Who Are at Risk of Progression to Severe Disease.
Open to recruitment
Aim of the study: The purpose of the study is to evaluate the safety, pharmacokinetics, and efficacy of nirmatrelvir/ritonavir for the treatment of non-hospitalised, symptomatic paediatric participants with COVID-19 who are at risk of progression to severe disease.
- Male or female participants:
Cohort 1: Weight ≥40 kg
- ≥12 to <18 years
- ≥6 to <12 years
Cohort 2: Weight ≥20 kg to <40 kg, ≥6 to <18 years
Cohort 3: ≥2 to <6 years
Cohort 4: ≥1 month to <2 years
Cohort 5: <1 month
- From birth (term newborn neonates gestational age 37 weeks or greater at the time of screening) to <18 years of age
- Negative urine pregnancy test for female participants who are biologically capable of having children.
- Female participant of childbearing potential or male participant able to father children who is willing to use a highly effective method of contraception as outlined in this protocol for at least 28 days after the last dose of study intervention if at risk of pregnancy with her/his partner.
- Ability to swallow tablets confirmed by participants’ parent(s)/legal guardian(s) for Cohorts 1 and 2 using this presentation of nirmatrelvir/ritonavir. An age-appropriate formulation will be developed for subsequent cohorts.
- Confirmed SARS-CoV-2 infection as determined by RT-PCR or another method of diagnosis approved by a health authority in any specimen collected within 72 hours prior to enrolment and initial onset of signs/symptoms attributable to COVID-19 within 5 days prior to the day of enrolment and at least 1 of the specified signs/symptoms attributable to COVID-19 present on the day of enrolment.
- Has at least 1 characteristic or underlying medical condition associated with an increased risk of developing severe illness from COVID-19 including:
Risk factors for severe COVID-19 disease <18 years of age:
- Overweight or Obese
- Current smoker
- Immunosuppressive disease (eg, bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications
- Chronic lung disease
- Known diagnosis of hypertension
- Cardiovascular disease
- Type 1 or type 2 diabetes mellitus
- Chronic kidney disease
- Sickle cell disease
- Neurodevelopmental disorders or other conditions that confer medical complexity
- Active cancer, other than localised skin cancer
- Infants (<1 year of age)
- Any new criteria identified by the CDC as risk factor for severe COVID-19 for paediatric participants
- History of hospitalisation for the medical treatment of COVID-19.
- Current need for hospitalisation or anticipated need for hospitalisation within 48 hours after enrolment in the clinical opinion of the site investigator.
- Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention.
- Any comorbidity requiring hospitalisation and/or surgery within 7 days prior to study entry, or that is considered life threatening within 30 days prior to study entry, as determined by the investigator.
- History of hypersensitivity or other contraindication to any of the components of the study intervention, as determined by the investigator.
- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behaviour or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
- Current or expected use of any prohibited medication(s) or those unwilling/unable to use a permitted concomitant medication(s).
- Concomitant use of any medications or substances that are strong inducers of CYP3A4 are prohibited within 28 days prior to first dose of nirmatrelvir/ritonavir and during study treatment.
- Use of monoclonal antibody treatment or convalescent COVID-19 plasma at any time during the course of the study.
- Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 therapeutics, through the long- term follow-up visit.
- Previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer) or known prior participation in this trial or other trial involving nirmatrelvir/ritonavir.
- Known history of any of the following abnormalities in clinical laboratory tests (within past 6 months of the screening visit).
- Receiving dialysis or have known moderate to severe renal impairment.
- Females who are pregnant or breastfeeding.
- Participants who are direct descendants (child or grandchild) of investigational site staff members or Pfizer/BioNTech employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
- Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
What participating in the study involves:
Eligible participants with a confirmed diagnosis of COVID-19 infection enrolled in Cohort 1 (1a 12 to <18 years, 1b 6 to <12 years, weight ≥40 kg) will receive nirmatrelvir/ritonavir for 5 days (10 doses total). Participants enrolled in Cohort 2 (6 to <18 years, weight 10 to <40 kg) will receive a nirmatrelvir/ritonavir for 5 days (10 doses total). Enrolment in Cohorts 1b and 2 will start after pharmacokinetic (PK) data from samples from the first 3 participants enrolled in Cohort 1a are available and the dose is confirmed.
The total study duration is up to 5 weeks and includes a screening period of no more than 48 hours before baseline (Day 1), study intervention for a total of 5 days, efficacy assessments through Day 28, a safety follow-up period through Day 34, and continued collection of ongoing safety information through SAE resolution, as applicable.