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.

• ClinicalTrials.gov Identifier: NCT04535167
• Recruitment Status: Completed
• First Posted: September 1, 2020
• Last Update Posted: June 24, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

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
Viral Disease	Drug: PF-07304814; Drug: Placebo	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

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

Intervention 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: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 9, 2020
• Actual Primary Completion Date: June 7, 2021
• Actual Study Completion Date: June 7, 2021

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 :

1. Frequency of treatment-emergent adverse events (TEAEs) [ Time Frame: 0 hours up to 41 days ]
   Adverse Events (AEs)
2. Number of participants who withdraw due to treatment-emergent adverse events (TEAEs) [ Time Frame: 0 hours up to 41 days ]
   Adverse Events
3. Frequency of treatment-emergent adverse events (TEAEs), causally related to study intervention [ Time Frame: 0 hours up to 41 days ]
   Adverse Events
4. Frequency of treatment-emergent serious adverse events [ Time Frame: 0 hours up to 41 days ]
   Serious Adverse Events
5. Frequency of treatment-emergent infusion site reactions [ Time Frame: 0 hours up to 41 days ]
   Adverse Events
6. Magnitude of abnormal hematologic laboratory findings [ Time Frame: 0 hours up to 41 days ]
   Percent change in laboratory parameters
7. Frequency of abnormal chemistry values [ Time Frame: 0 hours up to 41 days ]
   Adverse Events
8. Frequency of abnormal hematologic laboratory findings [ Time Frame: 0 hours up to 41 days ]
   Adverse Events
9. Magnitude of abnormal urinalysis findings [ Time Frame: 0 hours up to 41 days ]
   Percent change in urinalysis parameters
10. Change from baseline in PR values [ Time Frame: 0 hours up to 41 days ]
    ECG parameters
11. Change from baseline in RR values [ Time Frame: 0 hours up to 41 days ]
    ECG parameters
12. Change from baseline in QTc values [ Time Frame: 0 hours up to 41 days ]
    ECG parameters
13. Change from baseline in QTcF values [ Time Frame: 0 hours up to 41 days ]
    ECG parameters
14. Change from baseline in QRS values [ Time Frame: 0 hours up to 41 days ]
    ECG parameters
15. Change from baseline in pulse rate measurements [ Time Frame: 0 hours up to 41 days ]
    Vital sign measurements
16. Change from baseline in temperature values [ Time Frame: 0 hours up to 41 days ]
    Vital sign measurements
17. Change from baseline in respiratory rate values [ Time Frame: 0 hours up to 41 days ]
    Vital sign measurements
18. Change from baseline in systolic blood pressure [ Time Frame: 0 hours up to 41 days ]
    Vital sign measurements
19. Change from baseline in diastolic blood pressure [ Time Frame: 0 hours up to 41 days ]
    Vital sign measurements
20. Change from baseline in pulse oximetry/SpO2 measurement [ Time Frame: 0 hours up to 41 days ]
    Vital sign measurements

Secondary Outcome Measures :

1. Change in concentration at 24 hours (C24 [end of infusion]) of PF-07304814 and PF-00835231 [ Time Frame: 0 to 28 hours ]
   plasma PK parameters
2. Change in concentration, dose normalised, at 24 hours (C24 (dn) [end of infusion]) of PF-07304814 and PF-00835231 [ Time Frame: 0 to 28 hours ]
   plasma PK parameters
3. Change in concentration at 120 hours (C120[end of infusion]) of PF-07304814 and PF-00835231 [ Time Frame: 0 to 126 hours ]
   plasma PK parameters
4. Change in maximum observed concentration (Cmax) of PF-07304814 and PF-00835231 [ Time Frame: 0 to 126 hours ]
   plasma PK parameters
5. Change in concentration at steady state (Css) of PF-07304814 and PF-00835231 [ Time Frame: 0 to 126 hours ]
   plasma PK parameters
6. Cumulative amount of unchanged drug excreted into urine (Ae) [ Time Frame: 0 to 36 hours ]
   urinary PK parameters (Cohort 2 only)
7. Percent of dose excreted as unchanged drug (Ae%) over dosing period [ Time Frame: 0 to 36 hours ]
   urinary PK parameters (Cohort 2 only)
8. Change in terminal half life (t1/2) of PF-07304814 and PF-00835231 [ Time Frame: 0 to 126 hours ]
   plasma PK parameters

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

• 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.

Contacts and Locations

Locations

United States, California

El Camino Health

Mountain View, California, United States, 94040

Palo Alto Medical Foundation

Mountain View, California, United States, 94040

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States, 92663

UC Davis Health Investigational Drug Pharmacy

Sacramento, California, United States, 95817

UC Davis Medical Center

Sacramento, California, United States, 95817

United States, Massachusetts

Massachusetts General Hospital Translational and Clinical Research Center

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital, Clinical Trials Pharmacy

Boston, Massachusetts, United States, 02114

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Tennessee

Regional One Health

Memphis, Tennessee, United States, 38103

Belgium

University Hospital Brugmann

Brussels, Belgium, 1020

Brazil

Santa Casa De Misericórdia de Belo Horizonte

Belo Horizonte, Minas Gerais, Brazil, 30150221

Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain, 28040

Hospital Universitario Virgen Del Rocio

Sevilla, Spain, 41013

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04535167
• Other Study ID Numbers: C4611001; 2020-003905-73 ( EudraCT Number )
• First Posted: September 1, 2020
• Last Update Posted: June 24, 2021
• Last Verified: June 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

COVID-19; SARS-COV-2

Additional relevant MeSH terms:

COVID-19; Virus Diseases; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases