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

Exclusion Criteria

• •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.
• •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.