Viral Disease Clinical Trial
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
| Verified date | April 2023 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Completed |
| Enrollment | 26 |
| Est. completion date | June 7, 2021 |
| Est. primary completion date | June 7, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 79 Years |
| Eligibility | - Inclusion Criteria: 1. Male or female participants between the ages of 18 and 79 years. 2. Confirmed SARS-CoV-2 infection. 3. Hospitalized for COVID-19. 4. 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 5. Total body weight >=50 kg (110 lb), BMI <40 kg/m2; BMI <35 kg/m2 for 76- 79 years. - Exclusion Criteria: 1. Evidence of critical illness, defined by at least one of the following: Respiratory failure, Multi-organ dysfunction/failure, Cardiac failure or septic shock 2. Participants that are anticipated by the study Investigator to progress to critical disease, including mechanical ventilation, within 24 hours of enrolment 3. 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. |
| Country | Name | City | State |
|---|---|---|---|
| Belgium | University Hospital Brugmann | Brussels | |
| Brazil | Santa Casa De Misericórdia de Belo Horizonte | Belo Horizonte | Minas Gerais |
| Spain | Hospital Universitario Fundacion Jimenez Diaz | Madrid | |
| Spain | Hospital Universitario Virgen Del Rocio | Sevilla | |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Massachusetts General Hospital Translational and Clinical Research Center | Boston | Massachusetts |
| United States | Massachusetts General Hospital, Clinical Trials Pharmacy | Boston | Massachusetts |
| United States | Regional One Health | Memphis | Tennessee |
| United States | El Camino Health | Mountain View | California |
| United States | Palo Alto Medical Foundation | Mountain View | California |
| United States | Hoag Memorial Hospital Presbyterian | Newport Beach | California |
| United States | UC Davis Health Investigational Drug Pharmacy | Sacramento | California |
| United States | UC Davis Medical Center | Sacramento | California |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
United States, Belgium, Brazil, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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 | |
| Primary | 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). | |
| Primary | 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) . | |
| Primary | 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). | |
| Primary | 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). | |
| Primary | 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). | |
| Primary | 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). | |
| Primary | 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). | |
| Primary | 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). | |
| Primary | 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) | |
| Primary | 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). | |
| Primary | 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) | |
| Primary | 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) | |
| Primary | 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) | |
| Primary | 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 | 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. | Pre-dose and 6 hours post-dose on Day 1; 24 hours; 48 hours; and/or early termination. | |
| Secondary | 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. | Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination. | |
| Secondary | 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. | Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination. | |
| Secondary | 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. | Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination. | |
| Secondary | 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. | Pre-dose on Day1; Day 2, 3, 5 and 6 (end of treatment day), 7 (Follow-up 1), and/or early termination. |
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