Clinical trial NCT05386472: A Study to Learn About the Study Medicine (Nirmatrelvir Plus Ritonavir) in Pregnant Women With COVID-19
Official title: A PHASE 1, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY, AND TOLERABILITY OF ORALLY ADMINISTERED NIRMATRELVIR/RITONAVIR IN PREGNANT WOMEN WITH MILD-TO-MODERATE COVID-19
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: COVID-19
Keywords: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)
Pregnancy
Paxlovid
Nirmatrelvir
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2022-05-23
Enrollment: 25
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this clinical trial is to learn about how study medicine (Paxlovid, which contains nirmatrelvir and ritonavir) is changed and eliminated from the body, as well as its safety, and the extent to which side effects can be tolerated for treatment of pregnant women with mild or moderate COVID-19 compared to non-pregnant women with mild or moderate COVID-19.

This study is seeking participants who:

* are expecting a healthy baby and are in their second or third trimester pregnancy and have mild or moderate COVID-19
* are not pregnant and have mild or moderate COVID-19.

All participants in this study will take Paxlovid by mouth every 12 hours for 5 days. We will study the experiences of people receiving the study medicine. This will help us decide if the study medicine is safe.

All participants will take part in this study for at least 34 days; pregnant participants will take part until their delivery, so that the study duration may be up to 6 months, depending on their delivery date.

During this time, participants will have 7to 8 visits and, if pregnant, a visit at delivery. Around 2 to 3 visits and the delivery visit will be done in person (at the clinic or at the participant's home). The other 5 visits may be done over the phone, unless in-person visit is necessary as decided by the doctor. Blood samples will be collected on the first 4 to 5 study visits (and at other study visits, if necessary).


Eligibility criteria: Inclusion Criteria:

* All cohorts: Mild-to-moderate COVID-19 infection confirmed in sample collected ≤5 days prior to enrollment; onset within 5 days prior to enrollment and presence of ≥1 sign/symptom on the day of enrollment.
* Cohorts 1\&2: Expecting single baby; Pregnant in 2nd trimester, 14 0/7 to 27 6/7 weeks of gestational age (Cohort 1) or 3rd trimester, ≥28 0/7 and ≤34 6/7 weeks of gestational age (Cohort 2), by ultrasound.
* All cohorts: Otherwise healthy participants who are determined by medical history, physical examination, and clinical judgment to be appropriate for inclusion in the study

Exclusion Criteria:

* All cohorts: Current need for hospitalization or anticipated need for hospitalization in the clinical opinion of the site investigator.
* Cohorts 1\&2: Prior/current major condition or illness of mother/fetus substantially increasing risk of study participation/completion or impacting pregnancy/fetal outcomes in investigator's judgement.
* All cohorts: Current use of any medications that are highly dependent on CYP3A4 for clearance, and which are contraindicated in combination with nirmatrelvir/ritonavir.
* All cohorts: Has received or is expected to receive monoclonal antibody treatment, convalescent COVID-19 plasma, or anti-viral treatment (eg, molnupiravir) for the current SARSCoV-2 infection.
* All cohorts: Participants with moderate to severe kidney impairment

Primary outcomes:
measure: Apparent Oral Clearance (CL/F)
timeFrame: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
measure: Apparent Volume of Distribution (Vz/F)
timeFrame: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)
timeFrame: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
measure: Plasma Decay Half-Life (t1/2)
timeFrame: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
measure: Observed Plasma Trough Concentration (Ctrough)
timeFrame: Day 1: 1-3 hour post-dose; Day 3: 4-8 hour post-dose; Day 4: 8 to less than 12 hour post dose; Day 5: 2-4 hour, 6-8 hour, 10 to less than 12 hour post dose.
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline up through Day 34
measure: Incidence of TEAEs, SAEs, and AEs leading to discontinuations
timeFrame: Baseline up through end of treatment (Day 5/Day 6)
Secondary outcomes:
measure: Number of participants with delivery at medical facility
timeFrame: At delivery of the baby
measure: Number of participants with delivery at home
timeFrame: At delivery of the baby
measure: Number of participants with delivery at other location
timeFrame: At delivery of the baby
measure: Number of participants with caesarean section delivery
timeFrame: At delivery of the baby
measure: Number of participants with vaginal delivery
timeFrame: At delivery of the baby
measure: Number of participants with complications during delivery
timeFrame: At delivery of the baby
measure: Number of full-term live deliveries
timeFrame: At delivery of the baby
measure: Number of premature live deliveries
timeFrame: At delivery of the baby
measure: Number of participants with stillbirths
timeFrame: At delivery of the baby
measure: Number of participants with spontaneous abortions
timeFrame: At delivery of the baby
measure: Number of participants with induced/elective abortions
timeFrame: At delivery of the baby
measure: Number of participants with unknown delivery
timeFrame: At delivery of the baby
measure: Number of aborted or stillborn fetuses with abnormal findings upon gross visual inspection
timeFrame: At delivery of the baby
measure: Gestational age of newborn infants
timeFrame: At birth
measure: Number of neonates with congenital malformation/anomaly or other neonatal problem
timeFrame: At birth
measure: Body weight of newborn infants
timeFrame: At birth
measure: Body length of newborn infants
timeFrame: At birth
measure: Head circumference of newborn infants
timeFrame: At birth
measure: Incidence of SAEs in newborn infants
timeFrame: Birth through 24 hours after birth or until Study Day 34 (whichever is later)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham/Center for Women's Reproductive Health
state: Alabama
city: Cutler Bay
country: United States
facility: Beautiful Minds Clinical Research Center
state: Florida
city: DeBary
country: United States
facility: Omega Research Debary
state: Florida
city: Orlando
country: United States
facility: Omega Research Orlando
state: Florida
city: Tampa
country: United States
facility: Santos Research Center
state: Florida
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Missoula
country: United States
facility: Boeson Research MSO
state: Montana
city: Missoula
country: United States
facility: Origin Health
state: Montana
city: League City
country: United States
facility: Maximos Ob/Gyn
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Clinical Neuroscience Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospital
state: Utah
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: