Healthy, Sickle Cell Anemia
Conditions
Keywords
Safety, Tolerability, Single ascending dose, Multiple dose, Pharmacokinetics, Phase 1, First in human, First in patient
Brief summary
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.
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.
Interventions
BIOLOGICALPlacebo
Participants will receive matching placebo
BIOLOGICALPF-07209326
Participants will receive SC or IV single ascending doses
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, 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.
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs |
| Percentage of subjects with laboratory abnormalities | Day 1 up to Day 85 (SAD) or Day 113 (MD) | Percentage of subjects with laboratory abnormalities |
| Number of subjects with change from baseline in vital signs | Day 1 up to Day 85 (SAD) or Day 85 (MD) | blood pressure, pulse rate, temperature, respiration rate |
| Number of subjects with change from baseline in electrocardiogram (ECG) parameters | Day 1 up to Day 85 (SAD) or Day 85 (MD) | Number of subjects with change from baseline in electrocardiogram (ECG) parameters |
| 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 injection site reactions |
| Percentage of subjects with infusion site reactions | Day 1 up to Day 11 post each dose (SD) | Percentage of subjects with infusion site reactions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SAD: Single Dose PK /Cmax | Day 1 up to Day 85 | Maximum serum concentration |
| SAD: Single Dose PK / DN Cmax | Day 1 up to Day 85 | Dose normalized Cmax |
| SAD: Single Dose PK / Tmax | Day 1 up to Day 85 | Time for Cmax |
| SAD: Single Dose PK / AUClast | Day 1 up to Day 85 | Area under the serum concentration time profile from time zero to the time of the last quantifiable concentration. |
| SAD: Single Dose PK / DN AUClast | Day 1 up to Day 85 | Dose normalized AUClast |
| SAD: Single Dose PK / AUCinf | Day 1 up to Day 85 | Area under the serum concentration time profile from time zero to infinity. |
| SAD: Single Dose PK / DN AUCinf | Day 1 up to Day 85 | Dose normalized AUCinf. |
| SAD: Single Dose PK / t½ | Day 1 up to Day 85 | Terminal half life |
| SAD: Single Dose PK / CL (IV only) | Day 1 up to Day 85 | Clearance |
| SAD: Single Dose PK / CL/F (SC only) | Day 1 up to Day 85 | Apparent clearance |
| SAD: Single Dose PK / Vss (IV only) | Day 1 up to Day 85 | Volume of distribution at steady state |
| SAD: Single Dose PK / Vz/F (SC only) | Day 1 up to Day 85 | Apparent volume of distribution at steady state |
| SAD: Single Dose PK / F (SC only) | Day 1 up to Day 85 | Apparent bioavailability |
| MD: AUCtau | Day 1 up to Day 22 | Area under the curve over the dosing interval tau (1 week) after the first and last doses |
| SAD:ADA and/or NAb | Day 1 up to Day 85 | Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions |
| MD:ADA and/or NAb | Day 1 up to Day 113 | Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions |
| Patient-reported VOC event rate and VOC day rate | Day 1 to 85 | Efficacy in SCD participants based on an electronic patient reported outcome. |
Countries
United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed