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

• Sponsor: Pfizer (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04255875
• Collaborator: (none)
• Enrollment: 54
• Locations: 12
• Arms: 3
• Anticipated Duration (Months): 36.4
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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; 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.

Study Design

• Study Type: Interventional
• Anticipated 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: Feb 5, 2020
• Anticipated Primary Completion Date: Feb 18, 2023
• Anticipated Study Completion Date: Feb 18, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

2. Percentage of subjects with laboratory abnormalities [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 [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 [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 [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 [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 [Day 1 up to Day 85]

   Maximum serum concentration

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

   Dose normalized Cmax

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

   Time for Cmax

4. 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.

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

   Dose normalized AUClast

6. SAD: Single Dose PK / AUCinf [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 [Day 1 up to Day 85]

   Dose normalized AUCinf.

8. SAD: Single Dose PK / t½ [Day 1 up to Day 85]

   Terminal half life

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

   Clearance

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

    Apparent clearance

11. SAD: Single Dose PK / Vss (IV only) [Day 1 up to Day 85]

    Volume of distribution at steady state

12. SAD: Single Dose PK / Vz/F (SC only) [Day 1 up to Day 85]

    Apparent volume of distribution at steady state

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

    Apparent bioavailability

14. 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

15. SAD:ADA and/or NAb [Day 1 up to Day 85]

    Frequency of anti-drug antibody (ADA) and/or neutralizing antibody (NAb) productions

16. MD:ADA and/or NAb [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 [Day 1 to 85]

    Efficacy in SCD participants based on an electronic patient reported outcome.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts 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.

1. Participants with a history of allergic or anaphylactic reaction to therapeutic or diagnostic protein.

2. 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.

1. Evidence or history of clinically significant orthostatic blood pressure changes.

2. 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.

3. Participants with a history of allergic or anaphylactic reaction to therapeutic or diagnostic protein.

4. History of sensitivity to heparin or heparin induced thrombocytopenia.

5. Administration of voxelotor within 4 weeks prior to screening or planned use during the study.

6. Administration of crizanlizumab within 12 weeks prior to screening or planned use during the study.

7. Planned transfusion during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Haven Clinical Research Unit	New Haven	Connecticut	United States	06511
2	Howard University College of Medicine	Washington	District of Columbia	United States	20060
3	Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
4	Lee Health - Golisano Children's Hospital of Southwest Florida	Fort Myers	Florida	United States	33908
5	Children's Healthcare of Atlanta - Egleston Hospital-Aflac Cancer and Blood Disorders Center	Atlanta	Georgia	United States	30322
6	University of Illinois at Chicago Clinical Research Center	Chicago	Illinois	United States	60612
7	University of Illinois at Chicago	Chicago	Illinois	United States	60612
8	Prism Research LLC dba Nucleus Network	Saint Paul	Minnesota	United States	55114
9	Columbia University Medical Center	New York	New York	United States	10032
10	CUMC Research Pharmacy	New York	New York	United States	10032
11	UT Physicians Comprehensive Sickle Cell Center Houston	Houston	Texas	United States	77004
12	Memorial Hermann clinical research unit	Houston	Texas	United States	77030

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT04255875
• Other Study ID Numbers: C4071001
• First Posted: Feb 5, 2020
• Last Update Posted: Aug 23, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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: Anemia, Sickle Cell

Study Results

No Results Posted as of Aug 23, 2022