Dose Escalation Study of PF-07209326 in Healthy Participants and Participants With Sickle Cell Disease

A RANDOMIZED, DOUBLE-BLIND, PLACEBO CONTROLLED EVALUATION OF SINGLE DOSES OF PF-07209326 IN HEALTHY PARTICIPANTS (SAFETY, TOLERABILITY, AND PHARMACOKINETICS [PK]) FOLLOWED BY AN OPEN LABEL, REPEAT DOSE EVALUATION IN SICKLE CELL DISEASE PARTICIPANTS (SAFETY, TOLERABILITY, PK AND EFFICACY)

This Phase 1 first-in-human, first-in-patient, single ascending dose and multiple dose study will be a randomized, double-blind, placebo-controlled investigation of the safety, tolerability, and pharmacokinetics of PF-07209326 in healthy participants and participants with sickle cell disease.

Study Overview

• Status: Completed
• Conditions: Healthy; Sickle Cell Anemia
• Intervention / Treatment: Biological: PF-07209326; Biological: PF-07209326; Biological: Placebo

Detailed Description

Part 1 will evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of single ascending doses of PF-07209326 delivered by subcutaneous injection or intravenous delivery in healthy volunteer participants. After establishing the safety and tolerability in healthy participants, Part 2 will evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of subcutaneously delivered multiple dose of PF-07209326 in participants with sickle cell disease.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • Howard University College of Medicine
  • Florida
    • Fort Myers, Florida, United States, 33908
      • Golisano Children's Hospital of Southwest Florida
    • Fort Myers, Florida, United States, 33908
      • Lee Health - Golisano Children's Hospital of Southwest Florida
    • Hollywood, Florida, United States, 33023
      • Foundation for Sickle Cell Disease Research
    • Hollywood, Florida, United States, 33024
      • Foundation for Sickle Cell Disease Research
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston Hospital-Aflac Cancer and Blood Disorders Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Clinical Research Center
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Prism Research LLC dba Nucleus Network
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Herbert Irving Pavilion
    • New York, New York, United States, 10032
      • CUMC Research Pharmacy
    • New York, New York, United States, 10032
      • CUIMC Research Pharmacy
  • Texas
    • Houston, Texas, United States, 77004
      • UT Physicians Comprehensive Sickle Cell Center Houston
    • Houston, Texas, United States, 77030
      • Memorial Hermann clinical research unit
    • Houston, Texas, United States, 77030
      • UT Physicians Comprehensive Sickle Cell Center Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria Health Participants:

1. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria Healthy Participants:

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, immunocompromised (or known disorder of the immune system), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
2. History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C antibody (HCVAb). Hepatitis B vaccination is allowed.
3. History of active or latent tuberculosis (TB) regardless of treatment or positive QuantiFeron TB test.

4. Participants with any of the following acute or chronic infections or infection history:

   • Any infection requiring treatment within 2 weeks prior to the screening visit.
   • Any infection requiring hospitalization, parenteral antimicrobial therapy within 30 days of the first dose of investigational product.
   • Any infection judged to be an opportunistic infection, within the past 6 months of the first dose of the investigational product.
   • Known active or history of frequent bacterial, viral, fungal, mycobacterial or other infections as determined by the PI.
   • Participants with a fever within the last 7 days prior to dosing.
5. Participants with a history of allergic or anaphylactic reaction to therapeutic or diagnostic protein.
6. Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.

Inclusion Criteria for SCD Participants

1. Participants between the ages of 16 and 70 years old with a confirmed diagnosis of stable sickle cell disease (HbSS or HBS β0 thalassemia).
2. Medical history of ≥2 and ≤ 10 medical utilization VOCs in 12 months prior to screening.
3. ≥75% of daily ePRO diary completion, over a minimum of 14 days during the screening period.
4. Fully vaccinated for COVID-19 in accordance with the Center for Disease Control guidance prior to Screening or must be negative for SARS-CoV-2 by polymerase chain reaction (PCR) within 72 hours of the Day 1 visit.
5. Body Mass Index (BMI) ≤34.9 kg/m2 and weight ≥50 kg.

Exclusion Criteria for SCD Participants

1. Evidence of ongoing uncontrolled clinically significant co-morbidity (e.g. intercurrent events that result in signs symptoms that have an adverse impact on the respective individual's usual function) hematological (non-SCD), renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including stroke within 2 years prior to screening), hepatic, psychiatric or neurological.
2. Evidence or history of cardiac disease includes myocardial infarction, clinically significant cardiac arrhythmia (eg, atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, supraventricular tachycardia, and ventricular tachycardia), left ventricular failure, unstable angina, and coronary artery bypass grafting.
3. History of cancer (other than cutaneous basal cell or carcinoma in-situ) in the previous 5 years.
4. Active infection with Hepatitis B or C or HIV. Individuals seropositive for infection with Hepatitis C must be negative for viral RNA by PCR on at least 2 determinations.
5. History of active or latent tuberculosis (TB) regardless of treatment or positive QuantiFeron TB test.
6. Major surgery <3 months prior to baseline or planned significant medical procedures during the study.

7. Participants with any of the following acute or chronic infections or infection history:

   • Any infection requiring systemic treatment within 2 weeks prior to the screening visit.
   • Any infection requiring hospitalization, parenteral antimicrobial therapy within 30 days of the first dose of investigational product.
   • Any infection judged to be an opportunistic infection, within the past 6 months of the first dose of the investigational product.
   • Known active or history of frequent viral, fungal or other infections as determined by the Investigator.
   • Participants with a fever within the last 7 days prior to dosing.
8. Evidence or history of clinically significant orthostatic blood pressure changes.
9. Other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
10. Participants with a history of allergic or anaphylactic reaction to therapeutic or diagnostic protein.
11. Administration of voxelotor within 4 weeks prior to screening or planned use during the study.
12. Administration of crizanlizumab within 12 weeks prior to screening or planned use during the study.
13. Planned transfusion during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Healthy Participants; Participants will receive single ascending doses of subcutaneous (SC) or intravenous PF-07209326	Biological: PF-07209326; Participants will receive SC or IV single ascending doses; Biological: PF-07209326; SCD participants will receive a multiple dose of subcutaneous PF-07209326
Placebo Comparator: Placebo Healthy Participants; Participants will receive matching placebo	Biological: Placebo; Participants will receive matching placebo
Experimental: Treatment for SCD; Participants will receive a multiple dose of subcutaneous PF-07209326	Biological: PF-07209326; Participants will receive SC or IV single ascending doses; Biological: PF-07209326; SCD participants will receive a multiple dose of subcutaneous PF-07209326

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs	Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs	Day 1 up to Day 85 (SAD) or Day 113 (MD)
Percentage of subjects with laboratory abnormalities	Percentage of subjects with laboratory abnormalities	Day 1 up to Day 85 (SAD) or Day 113 (MD)
Number of subjects with change from baseline in vital signs	blood pressure, pulse rate, temperature, respiration rate	Day 1 up to Day 85 (SAD) or Day 85 (MD)
Number of subjects with change from baseline in electrocardiogram (ECG) parameters	Number of subjects with change from baseline in electrocardiogram (ECG) parameters	Day 1 up to Day 85 (SAD) or Day 85 (MD)
Percentage of subjects with injection site reactions	Percentage of subjects with injection site reactions	Day 1 up to Day 11 post (SAD) Day 1 up to Day 85 (MD)
Percentage of subjects with infusion site reactions	Percentage of subjects with infusion site reactions	Day 1 up to Day 11 post each dose (SD)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAD: Single Dose PK /Cmax	Maximum serum concentration	Day 1 up to Day 85
SAD: Single Dose PK / DN Cmax	Dose normalized Cmax	Day 1 up to Day 85
SAD: Single Dose PK / Tmax	Time for Cmax	Day 1 up to Day 85
SAD: Single Dose PK / AUClast	Area under the serum concentration time profile from time zero to the time of the last quantifiable concentration.	Day 1 up to Day 85
SAD: Single Dose PK / DN AUClast	Dose normalized AUClast	Day 1 up to Day 85
SAD: Single Dose PK / AUCinf	Area under the serum concentration time profile from time zero to infinity.	Day 1 up to Day 85
SAD: Single Dose PK / DN AUCinf	Dose normalized AUCinf.	Day 1 up to Day 85
SAD: Single Dose PK / t½	Terminal half life	Day 1 up to Day 85
SAD: Single Dose PK / CL (IV only)	Clearance	Day 1 up to Day 85
SAD: Single Dose PK / CL/F (SC only)	Apparent clearance	Day 1 up to Day 85
SAD: Single Dose PK / Vss (IV only)	Volume of distribution at steady state	Day 1 up to Day 85
SAD: Single Dose PK / Vz/F (SC only)	Apparent volume of distribution at steady state	Day 1 up to Day 85
SAD: Single Dose PK / F (SC only)	Apparent bioavailability	Day 1 up to Day 85
MD: AUCtau	Area under the curve over the dosing interval tau (1 week) after the first and last doses	Day 1 up to Day 22
SAD:ADA and/or NAb	Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions	Day 1 up to Day 85
MD:ADA and/or NAb	Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions	Day 1 up to Day 113
Patient-reported VOC event rate and VOC day rate	Efficacy in SCD participants based on an electronic patient reported outcome.	Day 1 to 85

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2020
• Primary Completion (Actual): July 7, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: February 3, 2020
• First Submitted That Met QC Criteria: February 3, 2020
• First Posted (Actual): February 5, 2020

Study Record Updates

• Last Update Posted (Estimated): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; Phase 1; Tolerability; Single ascending dose; Multiple dose; First in human; First in patient
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: C4071001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No