First-In-Human Study To Evaluate Safety, Tolerability, And Pharmacokinetics Following Single Ascending And Multiple Ascending Doses of PF-07304814 In Hospitalized Participants With COVID-19.

NCT04535167 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: C46110012020-003905-73
• Study Type: interventional
• Target: 26
• Locations: 4 countries
• Sites: 13

Brief Summary

It is Phase 1b, 2-part, double-blind, placebo-controlled study to evaluate safety, tolerability, and pharmacokinetics of PF-07304814, in patients hospitalized with SARS-CoV-2 virus infection.

Conditions

Viral Disease

Keywords

COVID-19; SARS-COV-2

Outcome Measures

Primary Outcomes (20)

• Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD

  An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. An adverse event was considered a Treatment-Emergent Adverse Event (TEAE) if the event started during the effective duration of treatment.

  Day 1 to 37 days

• Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 2: MAD

  An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. An adverse event was considered a treatment-emergent adverse event (TEAE) if the event started during the effective duration of treatment.

  Day 1 to 41 days

• Number of Participants With Discontinuations From Study/Study Drug or Dose Reduction Due to TEAEs - Part 1: SAD

  An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment.

  Day 1 up to 37 days

• Number of Participants With Discontinuations From Study/Study Drug or Dose Reduction Due to TEAEs - Part 2: MAD

  An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a Treatment-Emergent Adverse Event (TEAE) if the event started during the effective duration of treatment.

  Day 1 to 41 days

• Number of Participants With Laboratory Abnormality Without Regard to Baseline Abnormality - Part 1: SAD

  Laboratory abnormalities reported in at least 1 participant are presented in this OM, including: Hematology - lymphocytes, basophiles; Clinical Chemistry - aspartate aminotransferase, alanine aminotransferase, calcium, bicarbonate, glucose, glucose -FASTING; Urinalysis - urine glucose, urine hemoglobin, urobilinogen and urine erythrocytes (per high power field). Baseline was the last pre-dose measurement. LLN = lower limit of normal, ULN = upper limit of normal.

  Day 1 up to 6 days

• Number of Participants With Laboratory Abnormality Without Regard to Baseline Abnormality - Part 2: MAD

  Laboratory abnormalities reported in at least 1 participant are presented in this OM, including: Hematology - lymphocytes hemoglobin, hematocrit, erythrocytes, ery. mean corpuscular volume, ery. mean corpuscular, hemoglobin; Clinical Chemistry - alanine aminotransferase, protein, albumin, urea nitrogen, creatinine, HDL cholesterol, triglycerides, calcium, phosphate, bicarbonate, glucose; Urinalysis - urine glucose, ketones, urine hemoglobin, urobilinogen, nitrite, leukocyte esterase, urine erythrocytes (per high power field), urine leukocytes (Scalar). Baseline was the last pre-dose measurement. LLN = lower limit of normal, ULN = upper limit of normal

  Day 1 up to 41 days

• Summary of Baseline and Change From Baseline in Systolic and Diastolic Blood Pressure at Day 1 (30 Minutes, 2 Hours, 6 Hour, and 12 Hours; 24 Hours [End of Treatment]), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  Absolute baseline values and changes from baseline in supine systolic and diastolic blood pressure were summarized by treatment and time post-dose. Blood pressure was assessed in the supine position after at least 5 minutes of rest in a quiet setting without distractions. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1), Day 1-30 minutes, 2 hours, 6 hour, and 12 hours; 24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2).

• Summary of Baseline and Change From Baseline in Systolic and Diastolic Blood Pressure at Day2,3,4,5, and 6 (120 Hours), Day7 (Follow-up 1), Day10 (Follow-up 2), Day14 (Follow-up 3), Between Day34-41 (Follow-up 4), and/or Early Termination - Part 2: MAD

  Absolute baseline values and changes from baseline in supine systolic and diastolic blood pressure were summarized by treatment and time post-dose. Blood pressure was assessed in the supine position after at least 5 minutes of rest in a quiet setting without distractions. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1), Day 2, 3, 4, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41) and/or early termination (ET) .

• Summary of Baseline and Change From Baseline in Pulse Rate at Day 1 (30 Minutes, 2 Hours, 6 Hour, and 12 Hours; 24 Hours [End of Treatment]), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  Absolute baseline values and changes from baseline in pulse rate were summarized by treatment and time post-dose. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1), 30 minutes, 2 hours, 6 hour, and 12 hours (post-dose Day 1); 24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2).

• Summary of Baseline and Change From Baseline in Pulse Rate at Day 2, 3, 4, 5, and 6 (120 Hours), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Between Day 34-41 (Follow-up 4), and/or Early Termination - Part 2: MAD

  Absolute baseline values and changes from baseline in pulse rate were summarized by treatment and time post-dose. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1); Day 2, 3, 4, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41) and/or early termination (ET).

• Summary of Baseline and Change From Baseline in Temperature at Day 1 (30 Minutes, 2 Hours, 6 Hour, and 12 Hours; 24 Hours [End of Treatment]), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  Absolute baseline values and changes from baseline in temperature were summarized by treatment and time post-dose. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1); 30 minutes, 2 hours, 6 hour, and 12 hours (post-dose Day1); 24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2).

• Summary of Baseline and Change From Baseline in Temperature at Day 2, 3, 4, 5, and 6 (120 Hours), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Between Day 34-41 (Follow-up 4), and/or Early Termination - Part 2: MAD

  Absolute baseline values and changes from baseline in temperature were summarized by treatment and time post-dose. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1); Day 2, 3, 4, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41) and/or early termination (ET).

• Summary of Baseline and Change From Baseline in Respiratory Rate at Day 1 (30 Minutes, 2 Hours, 6 Hour, and 12 Hours; 24 Hours [End of Treatment]), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  Absolute baseline values and changes from baseline in respiratory rate were summarized by treatment and time post-dose. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1); 30 minutes, 2 hours, 6 hour, and 12 hours (post-dose Day1); 24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2).

• Summary of Baseline and Change From Baseline in Respiratory Rate at Day 2, 3, 4, 5, and 6 (120 Hours), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Between Day 34-41 (Follow-up 4), and/or Early Termination - Part 2: MAD

  Absolute baseline values and changes from baseline in respiratory rate were summarized by treatment and time post-dose. Baseline was defined as the last pre-dose measurement.

  Baseline (pre-dose Day 1); Day 2, 3, 4, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41) and/or early termination (ET).

• Summary of Baseline and Change From Baseline in Pulse Oximetry/SpO2 at 24 Hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  Percent SpO2 values at baseline and changes from baseline were summarized for participants in 3 categories: (1) participants who received supplemental oxygen throughout, (2) participants who received supplemental oxygen at some point during the study, and (3) participants who never received supplemental oxygen. Baseline of pulse oximetry/SpO2 was defined as the last pre-dose measurement. SpO2 = arterial oxygen saturation.

  Baseline (pre-dose Day 1); Day1-24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2)

• Summary of Baseline and Change From Baseline in Pulse Oximetry/SpO2 at Day 2, 3, 4, 5; 6 (120hours), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (Between Day 34-41), and/or Early Termination-Part 2: MAD

  Percent SpO2 values at baseline and changes from baseline were summarized for participants in 3 categories: (1) participants who received supplemental oxygen throughout, (2) participants who received supplemental oxygen at some point during the study, and (3) participants who never received supplemental oxygen. Baseline of pulse oximetry/SpO2 was defined as the last pre-dose measurement. SpO2 = arterial oxygen saturation.

  Baseline (pre-dose Day 1); Day 2, 3, 4, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41), and/or early termination (ET).

• Summary of Baseline and Change From Baseline in ECG Mean Heart Rate at Day 1 (30 Minutes, 2 Hours, 6 Hour, and 12 Hours; 24 Hours [End of Treatment]), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  The average of the triplicate readings collected at each assessment time was calculated for each ECG parameter. Baseline was defined as the average (if possible) of the triplicate pre-dose recordings on Day 1. Only centrally read ECG data was used.

  Baseline (pre-dose Day 1); 30 minutes, 2 hours, 6 hour, and 12 hours (post-dose Day1); 24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2)

• Summary of Baseline and Change From Baseline in ECG Mean Heart Rate at Day 2, 3, 5, 6 (120 Hours), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (Between Day 34-41) and/or Early Termination- Part 2: MAD

  The average of the triplicate readings collected at each assessment time was calculated for each ECG parameter. Baseline was defined as the average (if possible) of the triplicate pre-dose recordings on Day 1. Only centrally read ECG data was used.

  Baseline (pre-dose Day 1); Day 2, 3, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41), and/or early termination(ET)

• Summary of Baseline and Change From Baseline in PR, QRS, QT and QTcF Intervals at Day 1 (30 Minutes, 2 Hours, 6 Hour, and 12 Hours; 24 Hours [End of Treatment]), Day 3 (Follow-up 1) and Day 6 (Follow-up 2) - Part 1: SAD

  The average of the triplicate readings collected at each assessment time was calculated for each ECG parameter. Baseline was defined as the average (if possible) of the triplicate pre-dose recordings on Day 1. Only centrally read ECG data was used.

  Baseline (pre-dose Day 1); 30 minutes, 2 hours, 6 hour, and 12 hours (post-dose Day1); 24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2)

• Summary of Baseline and Change From Baseline in PR, QRS, QT and QTcF Intervals at Day 2, 3, 5, 6 (120 Hours), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (Between Day 34-41) and/or Early Termination- Part 2: MAD

  The average of the triplicate readings collected at each assessment time was calculated for each ECG parameter. Baseline was defined as the average (if possible) of the triplicate pre-dose recordings on Day 1. Only centrally read ECG data was used.

  Baseline (pre-dose Day 1); Day 2, 3, 5; 120 hours (End of Treatment), Day 7 (Follow-up 1), Day 10 (Follow-up 2), Day 14 (Follow-up 3), Follow-up 4 (between Day 34-41), and/or early termination(ET)

Secondary Outcomes (5)

• PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at 24 Hours (End of Infusion) - Part 1: SAD

  Pre-dose and 6 hours post-dose on Day 1; 24 hours; 48 hours; and/or early termination.

• PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameter: Concentration at 120 Hours (End of Infusion) - Part 2: MAD

  Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.

• PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Maximum Observed Concentration (Cmax) - Part 2: MAD

  Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.

• PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: t½ - Part 2: MAD

  Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.

• PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at Steady State (Css) - Part 2: MAD

  Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.

Study Arms (2)

PF-07304814

EXPERIMENTAL

Part 1: Cohort 1-5 Part 2: Cohort 6-9

Drug: PF-07304814

Placebo

PLACEBO COMPARATOR

Part 1: Cohort 1-5 Part 2: Cohort 6-9

Drug: Placebo

Interventions

PF-07304814 DRUG

PF-07304814 is an anti-viral, formulated for intravenous delivery

PF-07304814

Placebo DRUG

Placebo will be formulated for intravenous delivery

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants between the ages of 18 and 79 years.
• Confirmed SARS-CoV-2 infection.
• Hospitalized for COVID-19.
• Symptoms consistent with COVID-19 indicated by at least 1 of the following: fever, cough, sore throat, malaise, headache, muscle pain, shortness of breath, new loss of taste and smell, nausea, chills, fatigue, rhinorrhea, diarrhea, vomiting or radiographic infiltrates by imaging consistent with COVID-19
• Total body weight \>=50 kg (110 lb), BMI \<40 kg/m2; BMI \<35 kg/m2 for 76- 79 years.

You may not qualify if:

• Evidence of critical illness, defined by at least one of the following: Respiratory failure, Multi-organ dysfunction/failure, Cardiac failure or septic shock
• Participants that are anticipated by the study Investigator to progress to critical disease, including mechanical ventilation, within 24 hours of enrolment
• Participants with pre-existing moderate to severe cardiovascular disease, uncontrolled diabetes, or severe asthma or severe COPD.
• Participants with a known medical history of recent acute or chronic liver disease (other than NASH), chronic or active hepatitis B or C infection, or primary biliary cirrhosis.
• Participants with a known medical history of ischemic heart disease, heart failure, dysrhythmia or other pre-existing cardiac condition.
• \. Participants with known HIV infection, acute or chronic history of hepatitis B or C.
• Participants with a known medical history of recurrent seizures. 7. Participants with history of venous thromboembolic event, including deep venous thrombosis or pulmonary embolism 8.Confirmed concurrent active systemic infection other than COVID-19. 9.Current diagnosis of cancer, unless in remission and untreated. 10.Other medical or psychiatric condition including recent or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation 11.Females who are pregnant or breastfeeding.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (13)

El Camino Health

Mountain View, California, 94040, United States

Location

Palo Alto Medical Foundation

Mountain View, California, 94040, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

UC Davis Health Investigational Drug Pharmacy

Sacramento, California, 95817, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Massachusetts General Hospital Translational and Clinical Research Center

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital, Clinical Trials Pharmacy

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Regional One Health

Memphis, Tennessee, 38103, United States

Location

University Hospital Brugmann

Brussels, 1020, Belgium

Location

Santa Casa De Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, 30150221, Brazil

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario Virgen Del Rocio

Seville, 41013, Spain

Location

Related Publications (2)

• Robinson P, Toussi SS, Aggarwal S, Bergman A, Zhu T, Hackman F, Sathish JG, Updyke L, Loudon P, Krishna G, Clevenbergh P, Hernandez-Mora MG, Cisneros Herreros JM, Albertson TE, Dougan M, Thacker A, Baniecki ML, Soares H, Whitlock M, Nucci G, Menon S, Anderson AS, Binks M. Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Intravenous Infusions of PF-07304814 (Lufotrelvir) in Participants Hospitalized With COVID-19. Open Forum Infect Dis. 2023 Jul 10;10(8):ofad355. doi: 10.1093/ofid/ofad355. eCollection 2023 Aug.

  PMID: 37559753 DERIVED

• Crosas-Molist E, Samain R, Kohlhammer L, Orgaz JL, George SL, Maiques O, Barcelo J, Sanz-Moreno V. Rho GTPase signaling in cancer progression and dissemination. Physiol Rev. 2022 Jan 1;102(1):455-510. doi: 10.1152/physrev.00045.2020. Epub 2021 Sep 20.

  PMID: 34541899 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Virus Diseases; COVID-19

Interventions

lufotrelvir

Condition Hierarchy (Ancestors)

Infections; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 will have 2 planned cohorts. Each escalating cohort will be initiated for enrollment after assessment of safety, tolerability and PK data from previous cohorts by an independent IRC and is deemed acceptable. Part 2 will have 2 planned cohort and each escalating cohort will be initiated after all safety, tolerability and PK data from previous cohort is evaluated and is deemed acceptable by a competent regulatory authority.

Study Record Dates

• First Submitted: August 21, 2020
• First Posted: September 1, 2020
• Study Start: September 9, 2020
• Primary Completion: June 7, 2021
• Study Completion: June 7, 2021
• Last Updated: May 3, 2023
• Results First Posted: May 3, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); BR (1); US (9); ES (2)