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

Healthy Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04255875
• Other study ID #: C4071001
• Status: Completed
• Phase: Phase 1
• Start date: February 5, 2020
• Est. completion date: July 7, 2023

Study information

• Verified date: December 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: July 7, 2023
• Est. primary completion date: July 7, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

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 ß0 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.

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Healthy
• Sickle Cell Anemia

Intervention

Biological:
• Placebo
Participants will receive matching placebo
• PF-07209326
Participants will receive SC or IV single ascending doses
• PF-07209326
SCD participants will receive a multiple dose of subcutaneous PF-07209326

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Percentage of subjects with laboratory abnormalities	Percentage of subjects with laboratory abnormalities	Day 1 up to Day 85 (SAD) or Day 113 (MD)
Primary	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)
Primary	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)
Primary	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)
Primary	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	SAD: Single Dose PK /Cmax	Maximum serum concentration	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / DN Cmax	Dose normalized Cmax	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / Tmax	Time for Cmax	Day 1 up to Day 85
Secondary	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
Secondary	SAD: Single Dose PK / DN AUClast	Dose normalized AUClast	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / AUCinf	Area under the serum concentration time profile from time zero to infinity.	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / DN AUCinf	Dose normalized AUCinf.	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / t½	Terminal half life	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / CL (IV only)	Clearance	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / CL/F (SC only)	Apparent clearance	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / Vss (IV only)	Volume of distribution at steady state	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / Vz/F (SC only)	Apparent volume of distribution at steady state	Day 1 up to Day 85
Secondary	SAD: Single Dose PK / F (SC only)	Apparent bioavailability	Day 1 up to Day 85
Secondary	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
Secondary	SAD:ADA and/or NAb	Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions	Day 1 up to Day 85
Secondary	MD:ADA and/or NAb	Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions	Day 1 up to Day 113
Secondary	Patient-reported VOC event rate and VOC day rate	Efficacy in SCD participants based on an electronic patient reported outcome.	Day 1 to 85

External Links

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