Phase 1
Completed N=25
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.
Viral Disease
Source: ClinicalTrials.gov NCT04535167 ↗
Enrolled (actual)
25
Serious AEs
28.0%
Results posted
May 2023
Primary outcomePrimary: Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD — 1; 1; 2; 2 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 1: SAD |
1; 1; 2; 2; 0; 0 | — |
| PRIMARY Number of Participants With TEAEs, SAEs, and Severe TEAEs - Part 2: MAD |
2; 4; 3; 0; 0; 1 | — |
| PRIMARY Number of Participants With Discontinuations From Study/Study Drug or Dose Reduction Due to TEAEs - Part 1: SAD |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Discontinuations From Study/Study Drug or Dose Reduction Due to TEAEs - Part 2: MAD |
0; 0; 1; 0; 0; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormality Without Regard to Baseline Abnormality - Part 1: SAD |
1; 2; 0; 1; 0; 0 | — |
| PRIMARY Number of Participants With Laboratory Abnormality Without Regard to Baseline Abnormality - Part 2: MAD |
0; 2; 1; 0; 2; 0 | — |
| 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 |
116.0; 134.5; 108.0; 127.5; 6.0; -12.5 | — |
| 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 |
105.3; 127.6; 116.5; 4.8; 1.4; -4.3 | — |
| 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 |
83.0; 74.5; 66.0; 75.5; 1.0; 10.0 | — |
| 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 |
74.2; 80.9; 90.3; -4.0; -5.4; -1.5 | — |
| 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 |
37.6; 37.0; 36.5; 37.1; 0.2; -0.2 | — |
| 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 |
36.7; 36.7; 36.3; -0.4; -0.3; 0.2 | — |
| 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 |
21.0; 20.5; 23.0; 20.0; 0.0; -1.0 | — |
| 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 |
23.5; 22.4; 21.0; -3.0; -1.7; -0.5 | — |
| 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 |
92.0; 90.0; 98.0; 94.5; 91.0; 95.0 | — |
| 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 |
93.3; 96.3; 60.0; 97.0; 96.0; 97.3 | — |
| 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 |
87.5; 71.5; 66.0; 71.0; -3.5; -5.5 | — |
| 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 |
70.2; 80.1; 85.0; -4.7; -6.0; -0.7 | — |
| 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 |
153.0; 165.0; 171.0; 183.5; -7.0; -1.5 | — |
| 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 |
145.7; 139.7; 156.0; 3.8; -5.0; 1.3 | — |
| SECONDARY PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at 24 Hours (End of Infusion) - Part 1: SAD |
NA; NA; NA; NA | — |
| SECONDARY PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameter: Concentration at 120 Hours (End of Infusion) - Part 2: MAD |
197.2; 91.64; 1338; 800.8 | — |
| SECONDARY PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Maximum Observed Concentration (Cmax) - Part 2: MAD |
345.3; 272.6; 2382; 1265 | — |
| SECONDARY PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: t½ - Part 2: MAD |
1.79; 2.317 | — |
| SECONDARY PF-07304814 (Prodrug) and PF-00835231 (Active Moiety) Plasma PK Parameters: Concentration at Steady State (Css) - Part 2: MAD |
229.2; 102.2; 1720; 970.2 | — |
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.
- 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.
Data sourced from ClinicalTrials.gov (NCT04535167). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.