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

This is an interventional basic science trial for Healthy focused on measuring Safety, Tolerability, Single ascending dose, Multiple dose, Pharmacokinetics, Phase 1, First in human, First in patient Read More

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 18 and 65 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 or history of clinically significant hematological (non-SCD), renal, endocrine, pulmonary, gastrointestinal, cardiovascular (including overt stroke but excluding silent infarct), hepatic (excluding cholelithiasis), psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
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 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 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. History of sensitivity to heparin or heparin induced thrombocytopenia.
12. Administration of voxelotor within 4 weeks prior to screening or planned use during the study.
13. Administration of crizanlizumab within 12 weeks prior to screening or planned use during the study.
14. Planned transfusion during the study.