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.
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PF-07304814 Part 1: Cohort 1-5 Part 2: Cohort 6-9 |
Drug: PF-07304814
PF-07304814 is an anti-viral, formulated for intravenous delivery
|
| Placebo Comparator: Placebo Part 1: Cohort 1-5 Part 2: Cohort 6-9 |
Drug: Placebo
Placebo will be formulated for intravenous delivery
|
Outcome Measures
Primary Outcome Measures
- Frequency of treatment-emergent adverse events (TEAEs) [0 hours up to 41 days]
Adverse Events (AEs)
- Number of participants who withdraw due to treatment-emergent adverse events (TEAEs) [0 hours up to 41 days]
Adverse Events
- Frequency of treatment-emergent adverse events (TEAEs), causally related to study intervention [0 hours up to 41 days]
Adverse Events
- Frequency of treatment-emergent serious adverse events [0 hours up to 41 days]
Serious Adverse Events
- Frequency of treatment-emergent infusion site reactions [0 hours up to 41 days]
Adverse Events
- Magnitude of abnormal hematologic laboratory findings [0 hours up to 41 days]
Percent change in laboratory parameters
- Frequency of abnormal chemistry values [0 hours up to 41 days]
Adverse Events
- Frequency of abnormal hematologic laboratory findings [0 hours up to 41 days]
Adverse Events
- Magnitude of abnormal urinalysis findings [0 hours up to 41 days]
Percent change in urinalysis parameters
- Change from baseline in PR values [0 hours up to 41 days]
ECG parameters
- Change from baseline in RR values [0 hours up to 41 days]
ECG parameters
- Change from baseline in QTc values [0 hours up to 41 days]
ECG parameters
- Change from baseline in QTcF values [0 hours up to 41 days]
ECG parameters
- Change from baseline in QRS values [0 hours up to 41 days]
ECG parameters
- Change from baseline in pulse rate measurements [0 hours up to 41 days]
Vital sign measurements
- Change from baseline in temperature values [0 hours up to 41 days]
Vital sign measurements
- Change from baseline in respiratory rate values [0 hours up to 41 days]
Vital sign measurements
- Change from baseline in systolic blood pressure [0 hours up to 41 days]
Vital sign measurements
- Change from baseline in diastolic blood pressure [0 hours up to 41 days]
Vital sign measurements
- Change from baseline in pulse oximetry/SpO2 measurement [0 hours up to 41 days]
Vital sign measurements
Secondary Outcome Measures
- Change in concentration at 24 hours (C24 [end of infusion]) of PF-07304814 and PF-00835231 [0 to 28 hours]
plasma PK parameters
- Change in concentration, dose normalised, at 24 hours (C24 (dn) [end of infusion]) of PF-07304814 and PF-00835231 [0 to 28 hours]
plasma PK parameters
- Change in concentration at 120 hours (C120[end of infusion]) of PF-07304814 and PF-00835231 [0 to 126 hours]
plasma PK parameters
- Change in maximum observed concentration (Cmax) of PF-07304814 and PF-00835231 [0 to 126 hours]
plasma PK parameters
- Change in concentration at steady state (Css) of PF-07304814 and PF-00835231 [0 to 126 hours]
plasma PK parameters
- Cumulative amount of unchanged drug excreted into urine (Ae) [0 to 36 hours]
urinary PK parameters (Cohort 2 only)
- Percent of dose excreted as unchanged drug (Ae%) over dosing period [0 to 36 hours]
urinary PK parameters (Cohort 2 only)
- Change in terminal half life (t1/2) of PF-07304814 and PF-00835231 [0 to 126 hours]
plasma PK parameters
Eligibility Criteria
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.
- Participants with known HIV infection, acute or chronic history of hepatitis B or
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | El Camino Health | Mountain View | California | United States | 94040 |
| 2 | Palo Alto Medical Foundation | Mountain View | California | United States | 94040 |
| 3 | Hoag Memorial Hospital Presbyterian | Newport Beach | California | United States | 92663 |
| 4 | UC Davis Health Investigational Drug Pharmacy | Sacramento | California | United States | 95817 |
| 5 | UC Davis Medical Center | Sacramento | California | United States | 95817 |
| 6 | Massachusetts General Hospital Translational and Clinical Research Center | Boston | Massachusetts | United States | 02114 |
| 7 | Massachusetts General Hospital, Clinical Trials Pharmacy | Boston | Massachusetts | United States | 02114 |
| 8 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
| 9 | Regional One Health | Memphis | Tennessee | United States | 38103 |
| 10 | University Hospital Brugmann | Brussels | Belgium | 1020 | |
| 11 | Santa Casa De Misericórdia de Belo Horizonte | Belo Horizonte | Minas Gerais | Brazil | 30150221 |
| 12 | Hospital Universitario Fundacion Jimenez Diaz | Madrid | Spain | 28040 | |
| 13 | Hospital Universitario Virgen Del Rocio | Sevilla | Spain | 41013 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C4611001
- 2020-003905-73