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

NCT ID: NCT04255875

Last Updated: 2023-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

52 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-05

Study Completion Date

2023-07-07

Brief Summary

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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

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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.

Conditions

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Healthy Sickle Cell Anemia

Keywords

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Safety Tolerability Single ascending dose Multiple dose Pharmacokinetics Phase 1 First in human First in patient

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
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.

Study Groups

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Treatment Healthy Participants

Participants will receive single ascending doses of subcutaneous (SC) or intravenous PF-07209326

Group Type EXPERIMENTAL

PF-07209326

Intervention Type BIOLOGICAL

Participants will receive SC or IV single ascending doses

Placebo Healthy Participants

Participants will receive matching placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type BIOLOGICAL

Participants will receive matching placebo

Treatment for SCD

Participants will receive a multiple dose of subcutaneous PF-07209326

Group Type EXPERIMENTAL

PF-07209326

Intervention Type BIOLOGICAL

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

Interventions

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Placebo

Participants will receive matching placebo

Intervention Type BIOLOGICAL

PF-07209326

Participants will receive SC or IV single ascending doses

Intervention Type BIOLOGICAL

PF-07209326

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

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1\. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lbs).


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

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.
Minimum Eligible Age

16 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

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New Haven Clinical Research Unit

New Haven, Connecticut, United States

Site Status

Howard University College of Medicine

Washington D.C., District of Columbia, United States

Site Status

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

Lee Health - Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

Site Status

Foundation for Sickle Cell Disease Research

Hollywood, Florida, United States

Site Status

Foundation for Sickle Cell Disease Research

Hollywood, Florida, United States

Site Status

Children's Healthcare of Atlanta - Egleston Hospital-Aflac Cancer and Blood Disorders Center

Atlanta, Georgia, United States

Site Status

University of Illinois at Chicago Clinical Research Center

Chicago, Illinois, United States

Site Status

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

Prism Research LLC dba Nucleus Network

Saint Paul, Minnesota, United States

Site Status

Columbia University Medical Center - Herbert Irving Pavilion

New York, New York, United States

Site Status

CUIMC Research Pharmacy

New York, New York, United States

Site Status

CUMC Research Pharmacy

New York, New York, United States

Site Status

UT Physicians Comprehensive Sickle Cell Center Houston

Houston, Texas, United States

Site Status

Memorial Hermann clinical research unit

Houston, Texas, United States

Site Status

UT Physicians Comprehensive Sickle Cell Center Houston

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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https://pmiform.com/clinical-trial-info-request?StudyID=C4071001

To obtain contact information for a study center near you, click here.

Other Identifiers

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C4071001

Identifier Type: -

Identifier Source: org_study_id