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

Phase 1

Completed

• Conditions: Healthy; Sickle Cell Anemia
• Interventions: Biological: PF-07209326; Biological: Placebo

• Registration Number: NCT04255875
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2020-02-03
• Study First Submitted QC: 2020-02-03
• Study Start: 2020-02-05
• Study First Posted: 2020-02-05
• Primary Completion: 2023-07-07
• Study Completion: 2023-07-07
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-12
• Last Update Posted: 2023-12-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Treatment for SCD	PF-07209326	Participants will receive a multiple dose of subcutaneous PF-07209326
Placebo Healthy Participants	Placebo	Participants will receive matching placebo
Treatment Healthy Participants	PF-07209326	Participants will receive single ascending doses of subcutaneous (SC) or intravenous PF-07209326

Primary Outcome Measures

Name	Time	Method
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
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 infusion site reactions	Day 1 up to Day 11 post each dose (SD)	Percentage of subjects with infusion site reactions
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 laboratory abnormalities	Day 1 up to Day 85 (SAD) or Day 113 (MD)	Percentage of subjects with laboratory abnormalities

Secondary Outcome Measures

Name	Time	Method
SAD: Single Dose PK / DN AUClast	Day 1 up to Day 85	Dose normalized AUClast
SAD: Single Dose PK / Vss (IV only)	Day 1 up to Day 85	Volume of distribution at steady state
Patient-reported VOC event rate and VOC day rate	Day 1 to 85	Efficacy in SCD participants based on an electronic patient reported outcome.
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 / Vz/F (SC only)	Day 1 up to Day 85	Apparent volume of distribution at steady state
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 Cmax	Day 1 up to Day 85	Dose normalized Cmax
SAD: Single Dose PK / DN AUCinf	Day 1 up to Day 85	Dose normalized AUCinf.
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: Single Dose PK /Cmax	Day 1 up to Day 85	Maximum serum concentration
SAD: Single Dose PK / Tmax	Day 1 up to Day 85	Time for Cmax
MD:ADA and/or NAb	Day 1 up to Day 113	Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions
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 / F (SC only)	Day 1 up to Day 85	Apparent bioavailability
SAD:ADA and/or NAb	Day 1 up to Day 85	Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions

Trial Locations

Locations (14)

Prism Research LLC dba Nucleus Network; 🇺🇸 Saint Paul, Minnesota, United States

Howard University College of Medicine; 🇺🇸 Washington, District of Columbia, United States

Lee Health - Golisano Children's Hospital of Southwest Florida; 🇺🇸 Fort Myers, Florida, United States

Columbia University Medical Center - Herbert Irving Pavilion; 🇺🇸 New York, New York, United States

Golisano Children's Hospital of Southwest Florida; 🇺🇸 Fort Myers, Florida, United States

University of Illinois at Chicago Clinical Research Center; 🇺🇸 Chicago, Illinois, United States

Foundation for Sickle Cell Disease Research; 🇺🇸 Hollywood, Florida, United States

Children's Healthcare of Atlanta - Egleston Hospital-Aflac Cancer and Blood Disorders Center; 🇺🇸 Atlanta, Georgia, United States

CUIMC Research Pharmacy; 🇺🇸 New York, New York, United States

CUMC Research Pharmacy; 🇺🇸 New York, New York, United States

University of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States

Memorial Hermann clinical research unit; 🇺🇸 Houston, Texas, United States

New Haven Clinical Research Unit; 🇺🇸 New Haven, Connecticut, United States

UT Physicians Comprehensive Sickle Cell Center Houston; 🇺🇸 Houston, Texas, United States