Back to resultsFirst-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.
Primary Purpose
Viral Disease
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
PF-07304814
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Viral Disease focused on measuring COVID-19, SARS-COV-2
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
3.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.
4.Participants with a known medical history of ischemic heart disease, heart failure, dysrhythmia or other pre-existing cardiac condition.
5. Participants with known HIV infection, acute or chronic history of hepatitis B or C.
6.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.
Sites / Locations
- El Camino Health
- Palo Alto Medical Foundation
- Hoag Memorial Hospital Presbyterian
- UC Davis Health Investigational Drug Pharmacy
- UC Davis Medical Center
- Massachusetts General Hospital Translational and Clinical Research Center
- Massachusetts General Hospital, Clinical Trials Pharmacy
- Massachusetts General Hospital
- Regional One Health
- University Hospital Brugmann
- Santa Casa De Misericórdia de Belo Horizonte
- Hospital Universitario Fundacion Jimenez Diaz
- Hospital Universitario Virgen Del Rocio
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
PF-07304814
Placebo
Arm Description
Part 1: Cohort 1-5 Part 2: Cohort 6-9
Part 1: Cohort 1-5 Part 2: Cohort 6-9
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at 24 Hours (End of Infusion) - Part 1: SAD
C24 was defined as concentration at 24 hours. 24-hour PK draw was approximately 4 hours post end of infusion which corresponded to 28 hours.
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameter: Concentration at 120 Hours (End of Infusion) - Part 2: MAD
C120 was defined as concentration at 120 hours. Blood sample collection at approximately at 2 and 6 hours post the end of the infusion, which correspond to approximately 122 hours and 126 hours post the start of infusion.
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Maximum Observed Concentration (Cmax) - Part 2: MAD
Cmax was defined as maximum observed concentration. Blood sample collection at approximately 2 and 6 hours post the end of the infusion, which correspond to approximately 122 hours and 126 hours post the start of infusion.
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: t½ - Part 2: MAD
t½ was defined as terminal half-life. Blood sample collection at approximately within 30 minutes before end of infusion (~120 hours), and at 2 and 6 hours post the end of the infusion, which correspond to approximately 122h and 126h post the start of infusion.
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at Steady State (Css) - Part 2: MAD
Css was defined as concentration at steady state. Blood sample collection at approximately 2 and 6 hours post the end of the infusion, which correspond to approximately 122 hours and 126 hours post the start of infusion.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04535167
Brief Title
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.
Official Title
A PHASE 1B, 2-PART, DOUBLE-BLIND, PLACEBO-CONTROLLED, SPONSOR-OPEN STUDY, TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF SINGLE ASCENDING (24-HOUR, PART 1) AND MULTIPLE ASCENDING (120-HOUR, PART 2) INTRAVENOUS INFUSIONS OF PF-07304814 IN HOSPITALIZED PARTICIPANTS WITH COVID-19
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Completed
Study Start Date
September 9, 2020 (Actual)
Primary Completion Date
June 7, 2021 (Actual)
Study Completion Date
June 7, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
Detailed Description
It is a 2-part study in hospitalized COVID-19 patients.
Part 1 is to evaluate safety, tolerability, PK and markers of clinical activity of escalating doses of PF-07304814 given as 24-hour IV infusion.
2 planned and 3 optional cohorts with 8 participants each are planned.
Part 2 is to evaluate safety, tolerability, PK and markers of clinical activity of escalating doses of PF- 07304814 given as 120-hour infusion.
2 planned and 2 optional cohorts with 8 participants each are planned
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Viral Disease
Keywords
COVID-19, SARS-COV-2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Model Description
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.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-07304814
Arm Type
Experimental
Arm Description
Part 1:
Cohort 1-5
Part 2:
Cohort 6-9
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Part 1:
Cohort 1-5
Part 2:
Cohort 6-9
Intervention Type
Drug
Intervention Name(s)
PF-07304814
Intervention Description
PF-07304814 is an anti-viral, formulated for intravenous delivery
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo will be formulated for intravenous delivery
Primary Outcome Measure Information:
Title
Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD
Description
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.
Time Frame
Day 1 to 37 days
Title
Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 2: MAD
Description
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.
Time Frame
Day 1 to 41 days
Title
Number of Participants With Discontinuations From Study/Study Drug or Dose Reduction Due to TEAEs - Part 1: SAD
Description
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.
Time Frame
Day 1 up to 37 days
Title
Number of Participants With Discontinuations From Study/Study Drug or Dose Reduction Due to TEAEs - Part 2: MAD
Description
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.
Time Frame
Day 1 to 41 days
Title
Number of Participants With Laboratory Abnormality Without Regard to Baseline Abnormality - Part 1: SAD
Description
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.
Time Frame
Day 1 up to 6 days
Title
Number of Participants With Laboratory Abnormality Without Regard to Baseline Abnormality - Part 2: MAD
Description
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
Time Frame
Day 1 up to 41 days
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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) .
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
Baseline (pre-dose Day 1); Day1-24 hours (End of Treatment), Day 3 (Follow-up 1) and Day 6 (Follow-up 2)
Title
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
Description
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.
Time Frame
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).
Title
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
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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)
Title
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
Description
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.
Time Frame
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 Outcome Measure Information:
Title
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at 24 Hours (End of Infusion) - Part 1: SAD
Description
C24 was defined as concentration at 24 hours. 24-hour PK draw was approximately 4 hours post end of infusion which corresponded to 28 hours.
Time Frame
Pre-dose and 6 hours post-dose on Day 1; 24 hours; 48 hours; and/or early termination.
Title
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameter: Concentration at 120 Hours (End of Infusion) - Part 2: MAD
Description
C120 was defined as concentration at 120 hours. Blood sample collection at approximately at 2 and 6 hours post the end of the infusion, which correspond to approximately 122 hours and 126 hours post the start of infusion.
Time Frame
Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.
Title
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Maximum Observed Concentration (Cmax) - Part 2: MAD
Description
Cmax was defined as maximum observed concentration. Blood sample collection at approximately 2 and 6 hours post the end of the infusion, which correspond to approximately 122 hours and 126 hours post the start of infusion.
Time Frame
Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.
Title
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: t½ - Part 2: MAD
Description
t½ was defined as terminal half-life. Blood sample collection at approximately within 30 minutes before end of infusion (~120 hours), and at 2 and 6 hours post the end of the infusion, which correspond to approximately 122h and 126h post the start of infusion.
Time Frame
Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.
Title
PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at Steady State (Css) - Part 2: MAD
Description
Css was defined as concentration at steady state. Blood sample collection at approximately 2 and 6 hours post the end of the infusion, which correspond to approximately 122 hours and 126 hours post the start of infusion.
Time Frame
Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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.
3.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.
4.Participants with a known medical history of ischemic heart disease, heart failure, dysrhythmia or other pre-existing cardiac condition.
5. Participants with known HIV infection, acute or chronic history of hepatitis B or C.
6.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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
El Camino Health
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
Facility Name
Palo Alto Medical Foundation
City
Mountain View
State/Province
California
ZIP/Postal Code
94040
Country
United States
Facility Name
Hoag Memorial Hospital Presbyterian
City
Newport Beach
State/Province
California
ZIP/Postal Code
92663
Country
United States
Facility Name
UC Davis Health Investigational Drug Pharmacy
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
UC Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Massachusetts General Hospital Translational and Clinical Research Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Massachusetts General Hospital, Clinical Trials Pharmacy
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Regional One Health
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
University Hospital Brugmann
City
Brussels
ZIP/Postal Code
1020
Country
Belgium
Facility Name
Santa Casa De Misericórdia de Belo Horizonte
City
Belo Horizonte
State/Province
Minas Gerais
ZIP/Postal Code
30150221
Country
Brazil
Facility Name
Hospital Universitario Fundacion Jimenez Diaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital Universitario Virgen Del Rocio
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Citations:
PubMed Identifier
34541899
Citation
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.
Results Reference
derived
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4611001
Description
To obtain contact information for a study center near you, click here.
Learn more about this trial
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.
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