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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04255875
Recruitment Status : Recruiting
First Posted : February 5, 2020
Last Update Posted : March 29, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Healthy Sickle Cell Anemia Biological: Placebo Biological: PF-07209326 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, 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.
Primary Purpose: Basic Science
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)
Actual Study Start Date : February 5, 2020
Estimated Primary Completion Date : September 20, 2022
Estimated Study Completion Date : September 20, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Healthy Participants
Participants will receive single ascending doses of subcutaneous (SC) or intravenous PF-07209326
Biological: PF-07209326
Participants will receive SC or IV single ascending doses

Placebo Comparator: Placebo Healthy Participants
Participants will receive matching placebo
Biological: Placebo
Participants will receive matching placebo

Experimental: Treatment for SCD
Participants will receive a multiple dose of subcutaneous PF-07209326
Biological: PF-07209326
SCD participants will receive a multiple dose of subcutaneous PF-07209326




Primary Outcome Measures :
  1. Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs [ Time Frame: 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

  2. Percentage of subjects with laboratory abnormalities [ Time Frame: Day 1 up to Day 85 (SAD) or Day 113 (MD) ]
    Percentage of subjects with laboratory abnormalities

  3. Number of subjects with change from baseline in vital signs [ Time Frame: Day 1 up to Day 85 (SAD) or Day 85 (MD) ]
    blood pressure, pulse rate, temperature, respiration rate

  4. Number of subjects with change from baseline in electrocardiogram (ECG) parameters [ Time Frame: Day 1 up to Day 85 (SAD) or Day 85 (MD) ]
    Number of subjects with change from baseline in electrocardiogram (ECG) parameters

  5. Percentage of subjects with injection site reactions [ Time Frame: Day 1 up to Day 11 post (SAD) Day 1 up to Day 85 (MD) ]
    Percentage of subjects with injection site reactions

  6. Percentage of subjects with infusion site reactions [ Time Frame: Day 1 up to Day 11 post each dose (SD) ]
    Percentage of subjects with infusion site reactions


Secondary Outcome Measures :
  1. SAD: Single Dose PK /Cmax [ Time Frame: Day 1 up to Day 85 ]
    Maximum serum concentration

  2. SAD: Single Dose PK / DN Cmax [ Time Frame: Day 1 up to Day 85 ]
    Dose normalized Cmax

  3. SAD: Single Dose PK / Tmax [ Time Frame: Day 1 up to Day 85 ]
    Time for Cmax

  4. SAD: Single Dose PK / AUClast [ Time Frame: Day 1 up to Day 85 ]
    Area under the serum concentration time profile from time zero to the time of the last quantifiable concentration.

  5. SAD: Single Dose PK / DN AUClast [ Time Frame: Day 1 up to Day 85 ]
    Dose normalized AUClast

  6. SAD: Single Dose PK / AUCinf [ Time Frame: Day 1 up to Day 85 ]
    Area under the serum concentration time profile from time zero to infinity.

  7. SAD: Single Dose PK / DN AUCinf [ Time Frame: Day 1 up to Day 85 ]
    Dose normalized AUCinf.

  8. SAD: Single Dose PK / t½ [ Time Frame: Day 1 up to Day 85 ]
    Terminal half life

  9. SAD: Single Dose PK / CL (IV only) [ Time Frame: Day 1 up to Day 85 ]
    Clearance

  10. SAD: Single Dose PK / CL/F (SC only) [ Time Frame: Day 1 up to Day 85 ]
    Apparent clearance

  11. SAD: Single Dose PK / Vss (IV only) [ Time Frame: Day 1 up to Day 85 ]
    Volume of distribution at steady state

  12. SAD: Single Dose PK / Vz/F (SC only) [ Time Frame: Day 1 up to Day 85 ]
    Apparent volume of distribution at steady state

  13. SAD: Single Dose PK / F (SC only) [ Time Frame: Day 1 up to Day 85 ]
    Apparent bioavailability

  14. MD: AUCtau [ Time Frame: Day 1 up to Day 22 ]
    Area under the curve over the dosing interval tau (1 week) after the first and last doses

  15. SAD:ADA and/or NAb [ Time Frame: Day 1 up to Day 85 ]
    Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions

  16. MD:ADA and/or NAb [ Time Frame: Day 1 up to Day 113 ]
    Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions

  17. Patient-reported VOC event rate and VOC day rate [ Time Frame: Day 1 to 85 ]
    Efficacy in SCD participants based on an electronic patient reported outcome.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04255875


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Connecticut
New Haven Clinical Research Unit Active, not recruiting
New Haven, Connecticut, United States, 06511
United States, District of Columbia
Howard University Hospital Recruiting
Washington, District of Columbia, United States, 20060
United States, Florida
Golisano Children's Hospital of Southwest Florida Not yet recruiting
Fort Myers, Florida, United States, 33908
Lee Health - Golisano Children's Hospital of Southwest Florida Not yet recruiting
Fort Myers, Florida, United States, 33908
United States, Minnesota
Prism Research LLC dba Nucleus Network Active, not recruiting
Saint Paul, Minnesota, United States, 55114
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
CUMC Research Pharmacy Recruiting
New York, New York, United States, 10032
United States, Texas
UT Physicians Comprehensive Sickle Cell Center Houston Recruiting
Houston, Texas, United States, 77004
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04255875    
Other Study ID Numbers: C4071001
First Posted: February 5, 2020    Key Record Dates
Last Update Posted: March 29, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Safety
Tolerability
Single ascending dose
Multiple dose
Pharmacokinetics
Phase 1
First in human
First in patient
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn