NIRMATRELVIR for COVID-19 | SARS-CoV-2 infection

Inclusion criteria

• {"criterion_text":"- Male or female participants: • Cohort 1: Weight ≥40 kg a. ≥12 to <18 years b. ≥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 (≥28 days) to <2 years • Cohort 5: <1 month (<28 days) From birth (postmenstrual age of 44 weeks or greater weighing >2.6 kg 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 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 partner.Note: If the childbearing potential changes after start of the study (eg, a premenarchal female participant experiences menarche) or the risk of pregnancy changes (eg, a female participant who was not heterosexually active becomes active), the participant must discuss this with the investigator, who should determine if a female participant must begin a highly effective method of contraception. If reproductive status is questionable, additional evaluation should be considered."}
• {"criterion_text":"- Until oral powder is available for use, ability to swallow tablets confirmed by participants’ parent(s)/legal guardian(s) for Cohorts 1 and 2 using the presentation of nirmatrelvir/ritonavir supplied in the study."}
• {"criterion_text":"- 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 enrollment and initial onset of signs/symptoms attributable to COVID-19 within 5 days prior to the day of enrollment and at least 1 of the specified signs/symptoms attributable to COVID-19 present on the day of enrollment. Note: RT-PCR is the preferred method; however, with evolving approaches to confirmation of SARS-CoV-2 infection, other molecular or antigen tests that detect viral RNA or protein are allowed. The test result must be available to confirm eligibility. Participants may be enrolled based on positive results of a rapid SARS-CoV-2 antigen test performed at screening."}
• {"criterion_text":"- 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 (BMI [kg/m2] ≥85th percentile for age and gender based on CDC growth charts o For children <2 years of age, sex specific weight-for-length; • Current smoker (cigarette smoking within the past 30 days) and history of at least 100 lifetime cigarettes; • Immunosuppressive disease (eg, bone marrow or organ transplantation or primary immune deficiencies) OR prolonged use of immune-weakening medications: o Has received corticosteroids at a dose known to cause immune suppression, based on the clinical judgement of the investigator, for at least 14 days, within 30 days prior to study entry o Has received treatment with biologics (eg, infliximab, ustekinumab), immunomodulators (eg, methotrexate, 6MP, azathioprine) or cancer chemotherapy within 90 days prior to study entry o HIV infection with CD4 cell count <200 mm3 and a viral load lower than 400 copies/mL; • Chronic lung disease o If asthma, requires daily prescribed therapy; • Known diagnosis of hypertension; • Cardiovascular disease; • Type 1 or Type 2 diabetes mellitus; • Chronic kidney disease defined as eGFR between 45 to 89 mL/min/1.73m2 or eCrCl between 45 to 89 mL/min; • Sickle cell disease; • Neurodevelopmental disorders (eg, cerebral palsy, Down’s syndrome, ADHD, intellectual and developmental disabilities, learning disabilities, limitations with self-care of activities of daily living) or other conditions that confer medical complexity (eg, genetic or metabolic syndromes and severe congenital anomalies, congenital malformations); • Active cancer, other than localized skin cancer, including those requiring treatment as long as the treatment is not among the prohibited medications that must be administered/continued during the trial period; • Infants (<1 year of age); • Spinal cord injury • Any new criteria identified by the CDC as a risk factor for severe COVID-19 for pediatric participants."}

Exclusion criteria

• {"criterion_text":"- Hospitalization History of hospitalization for the medical treatment of current COVID-19 infection. • Current need for hospitalization or anticipated need for hospitalization for the treatment of COVID-19 within 48 hours after enrollment in the clinical opinion of the site investigator Note: Children hospitalized for quarantine only or who are in the hospital to receive treatment for other conditions may be eligible provided that all study procedures can be completed."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Known history of any of the following abnormality in clinical laboratory tests (within past 6 months of the screening visit): • Total bilirubin ≥2 X ULN (except for Gilbert’s syndrome)"}
• {"criterion_text":"- Receiving dialysis or have known moderate to severe renal impairment ie, eGFR <45 mL/min/1.73 m2 or eCrCl <45 mL/min) within 6 months of the screening visit using the age-appropriate calculation o If participant <1 month of age, use the Bedside Schwartz Equation; o If participant ≥1 month to <2 years of age, use the Bedside Schwartz Equation; o If participant ≥2 years to <12 years of age, use the Modified Schwartz Equation; o If participant is ≥12 years to <18 years of age and is either receiving dialysis or has known moderate to severe renal impairment (estimated creatinine clearance of <45 mL/min) within 6 months of the screening visit use the Cockcroft-Gault Formula. Note: If the investigator suspects the participant may have any of the above laboratory values, confirmatory tests should be performed at screening to confirm eligibility before the first dose of study intervention."}
• {"criterion_text":"- Females who are pregnant or breastfeeding"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention."}
• {"criterion_text":"- History of hypersensitivity or other contraindication to any of the components of the study intervention, as determined by the investigator."}
• {"criterion_text":"- Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study,"}
• {"criterion_text":"- Known medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic or active hepatitis B or C infection, primary biliary cirrhosis, Child Pugh Class B or C or acute liver failure."}
• {"criterion_text":"- Current or expected use of any prohibited medication(s) or those and that are highly dependent on CYP3A4 for clearance, and for which elevated plasma concentrations may be associated with serious and/or life-threatening events during treatment and for 4 days after the last dose of nirmatrelvir/ritonavir"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Use of monoclonal antibody treatment, antiviral treatment (eg, molnupiravir) or convalescent COVID-19 plasma for treatment of COVID-19 at any time during the course of the study and expectation to receive SARS-CoV-2 vaccine prior to Day 34 of the study."}
• {"criterion_text":"- Participating in another clinical study with an investigational compound or device, including those for COVID-19 therapeutics, through the long-term follow-up visit."}

Primary endpoints

• {"endpoint_text":"- Plasma nirmatrelvir PK parameters including Cmax, AUC0-tau, t1/2, and Ctrough.","definition_or_measurement_approach":"Plasma pharmacokinetic parameters measured in plasma (Cmax, AUC0-tau, t1/2, Ctrough) as listed."}
• {"endpoint_text":"- Incidence of TEAEs, SAEs, AEs leading to discontinuations, and vital sign measurements","definition_or_measurement_approach":"Incidence (frequency) of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events leading to discontinuation, and recorded vital sign measurements over study period."}

Secondary endpoints

• {"endpoint_text":"- SARS-CoV-2 viral RNA measured via RT-PCR in nasopharyngeal or nasal swabs over time","definition_or_measurement_approach":"Viral RNA quantified by RT-PCR on nasopharyngeal or nasal swab specimens collected over time."}
• {"endpoint_text":"- Proportion of participants with COVID-19 related hospitalization or death from any cause through Day 28","definition_or_measurement_approach":"Proportion (percentage) of participants experiencing COVID-19‑related hospitalization or death up to Day 28."}
• {"endpoint_text":"- Acceptability and palatability assessments of nirmatrelvir/ritonavir (filmcoated tablets and oral powder)","definition_or_measurement_approach":"Assessments of acceptability and palatability for film‑coated tablets and oral powder formulations as collected in study assessments."}

Methods

• Recruitment material: Flyer (documents: K2_2_Recruitment material_Flyer_C4671026_BG_EN_Public and K2_1...BG) — intended for caregivers/participants; English and Bulgarian versions available.
• Recruitment material: Poster (K3_2_Recruitment material_Poster_C4671026_BG_EN_Public and BG) — English and Bulgarian.
• Recruitment material: Brochure (K4_2_Recruitment material_Brochure_C4671026_BG_EN_Public and BG) — English and Bulgarian.
• HCP to Caregiver Letter (K5_2_Recruitment material_HCP to Caregiver Letter_C4671026_BG_EN_Public) — healthcare‑provider to caregiver recruitment channel; English and Bulgarian versions available.
• Informed Consent Flipchart (K6_2_Recruitment material_Informed Consent Flipchart_C4671026_BG EN_Public) — recruitment/consent support material; English and Bulgarian.

Bulgaria

Earliest CTIS Part Ii Submission Date

18-01-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

117

Number Of Sites

4

Number Of Participants

30

Hungary

Earliest CTIS Part Ii Submission Date

18-01-2024

Latest Decision Or Authorization Date

14-05-2024

Processing Time Days

117

Number Of Sites

1

Number Of Participants

9

Primary sponsor

Full Name

Pfizer Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Ppd Inc.

Responsibilities

sponsorDuties code: 4

Name

Premier Research International LLC

Responsibilities

Data Acquisition; Dictionary Coding

Name

Syneos Health Inc.

Responsibilities

sponsorDuties code: 11

Name

Parexel International Corp.

Responsibilities

sponsorDuties code: 14

Third parties

• {"country":"United States","full_name":"Ppd Inc.","duties_or_roles":"sponsorDuties code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Premier Research International LLC","duties_or_roles":"Data Acquisition; Dictionary Coding","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"sponsorDuties code: 11","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"York Bioanalytical Solutions Limited","duties_or_roles":"Biomarker Development and Bioanalysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Translation Services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"sponsorDuties code: 14","organisation_type":"Pharmaceutical company"}