Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 16 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Basic Science
Masking
Triple (Participant, Care Provider, Investigator)
Masking Description
Masking will only be applicable to Part 1 of the study where Healthy participants will be enrolled and randomized to receive either PF-07209326 or to placebo. In Part 2 of the study, all eligible SCD participants will receive PF-07209326 and no masking will be required.

Arm Groups

ArmDescriptionAssigned Intervention
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
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
    SCD participants will receive a multiple dose of subcutaneous PF-07209326

More Details

Status
Completed
Sponsor
Pfizer

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.