Study to Evaluate Safety and Tolerability of PF-07242813 in Healthy Participants and Participants With Atopic Dermatitis

NCT04668066 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4461001
• Study Type: interventional
• Target: 121
• Locations: 1 country
• Sites: 7

Brief Summary

This is the first time PF-07242813 will be given to humans. The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07242813 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07242813 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms.

Conditions

Atopic Dermatitis

Keywords

Atopic Dermatitis; inflammatory skin disease

Outcome Measures

Primary Outcomes (13)

• Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.

  From start of study treatment on Day 1 to Day 71

• Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs

  An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.

  From start of study treatment on Day 1 to Day 99

• Part 2: Number of Participants With TEAEs and TESAEs

  An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or other important medical events. An AE was considered as treatment emergent if the event started during the effective duration of treatment. All events that started on or after the first dosing day up to the last dose plus the lag time were considered as TEAEs.

  From start of study treatment on Day 1 to Week 16

• Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs

  Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.

  From initiation of treatment to day 71

• Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs

  Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.

  From start of study treatment on Day 1 to Day 99

• Part 2: Number of Participants With Clinically Significant Findings in Vital Signs

  Vital signs included blood pressure, pulse rate, respiratory rate and temperature. Temperature was measured by oral, tympanic, or temporal artery method. Blood pressure and respiratory rate were measured with the participant in a supine position after 5 minutes of rest for the participant. Clinically significant findings were determined by the investigator.

  From start of study treatment on Day 1 to Week 16

• Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities

  Pre-defined criteria for laboratory parameters were hemoglobin (HGB) (\<0.8\* Lower limit normal (LLN)), Erythrocyte (Ery). Mean Corpuscular (MC) Volume (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* Upper limit normal (ULN)), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.

  Baseline (last pre-dose measurement) to Day 71

• Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities

  Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.

  Baseline (last pre-dose measurement) to Day 99

• Part 2: Number of Participants With Laboratory Test Abnormalities

  Pre-defined criteria for laboratory parameters were HGB (\<0.8\* LLN), Ery MCV (\<0.9\* LLN), Ery MC Hemoglobin (\<0.9\* LLN), Ery. MC HGB Concentration (\<0.9\* LLN), Leukocytes (\<0.6\* LLN), Neutrophils (\<0.8\* LLN), Bilirubin (\>1.5\* ULN), Aspartate Aminotransferase (\>3.0\* ULN), Urea Nitrogen (\>1.3\* ULN), Creatinine (\>1.3\* ULN), Urate (\>1.2\* ULN). Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.

  Baseline (last pre-dose measurement) to Week 16

• Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities

  Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.

  From pre-dose up to 6 hours post dose on Day 1

• Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG)

  Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, corrected QT (QTc) intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.

  From pre-dose on Day 1 up to Day 71

• Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG

  Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.

  From pre-dose on Day 1 up to Day 99

• Part 2: Number of Participants With Clinically Significant Findings in ECG

  Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTc intervals and QRS complex. ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position. Clinically significant findings were determined by the investigator.

  From pre-dose on week 1 to week 16

Secondary Outcomes (10)

• Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for PF-07242813

  Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV

• Part 1: SAD Cohorts: Area Under the Serum Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for PF-07242813

  Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV

• Part 1: SAD Cohorts: Maximum Serum Concentration (Cmax) for PF-07242813

  Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV

• Part 1: SAD Cohorts: Time to Reach Maximum Concentration (Tmax) for PF-07242813

  Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV

• Part 1: SAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813

  Pre-dose, 2, 6, 12, 24, 48, 72, 96, 336, 672 hours post-dose (for all cohorts); 1008 hours post-dose for all cohorts except 0.3 mg IV; 1344 and 1680 hours post-dose for all cohorts except 0.3 mg IV and 1 mg IV

Study Arms (3)

Single ascending doses of PF-07242813 or placebo in healthy participants

EXPERIMENTAL

Participants will receive a single intravenous dose of either PF-07242813 or placebo

Drug: PF-07242813; Drug: Placebo

Multiple ascending doses of PF-07242813 or placebo in healthy participants

EXPERIMENTAL

Participants will receive multiple subcutaneous doses PF-07242813 or placebo

Drug: PF-07242813; Drug: Placebo

Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis

EXPERIMENTAL

Participants will receive a single intravenous dose of either PF-07242813 or placebo

Drug: PF-07242813; Drug: Placebo

Interventions

PF-07242813 DRUG

PF-07242813 given intravenously or subcutaneous

Multiple ascending doses of PF-07242813 or placebo in healthy participants; Single ascending doses of PF-07242813 or placebo in healthy participants; Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis

Placebo DRUG

Placebo given intravenously or subcutaneous

Multiple ascending doses of PF-07242813 or placebo in healthy participants; Single ascending doses of PF-07242813 or placebo in healthy participants; Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BMI of 17.5 to 30.5 kg/m2; and BW\>50 kg (110 lbs)
• Overtly healthy as determined by medical evaluation including medical history, physical examination, vital sign assessments, temperature, 12-lead ECGs, laboratory tests
• Japanese cohort: healthy adults of Japanese descent, where parents and grandparents are Japanese
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol
• Have a clinical diagnosis of chronic atopic dermatitis (also known as atopic eczema) for approximately 1 year prior to Day 1 and have the diagnosis of AD confirmed (Hanifin and Rajka criteria of AD).
• Either have had an inadequate response to treatment with topical medications (for at least 4 consecutive weeks within 1 year of the first dose of the study drug) OR Have a documented reason why topical treatments are considered medically inappropriate (eg, because of important side effects or safety risks) within the last year.
• Have moderate to severe AD (defined as having an affected BSA (captured as part of EASI) ≥10%, IGA ≥3, and EASI ≥12 at both the screening and baseline visits).
• Generally healthy adult, with no significant comorbidities.
• Mild or moderate asthma that is well-controlled (not requiring high dose inhaled corticosteroids, systemic \[oral or parenteral\] corticosteroids, or biologic asthma treatments).
• BMI of 17.5 to 40 kg/m2; and a total body weight \>50 kg (110 lbs).

You may not qualify if:

• Evidence of active, latent, or inadequately treated infection with TB; History of HIV, hepatitis B or C infection; positive testing for HIV, HepB, HepC except HepB vaccination
• Medical or psychiatric condition that may increase the risk of study participation, or inappropriate for the study in investigator's judgement
• History of any lymphoproliferative disorder, evidence or history of clinically significant diseases
• History of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or judged clinically significant by the investigator within 6 months
• Known history of or evidence of current endocrine disease
• Exposure to live or attenuated vaccines within 28 days of screening.
• Have any malignancies or a history of malignancies except adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin, or cervical carcinoma in situ.
• Allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Have undergone significant trauma or major surgery within 1 month of 1st dose of study drug.
• Use of prescription or nonprescription drugs, dietary or herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to 1st dose of study drug.
• Females taking hormone replacement therapy may be eligible to participate in this study if they are willing to discontinue therapy at least 28 days prior to the first dose of study treatment and remain off hormonal therapy for the duration of the study.
• Positive urine drug test, alcohol intake more than 14 units per week or use of tobacco/nicotine containing products more than 5 cigarettes per day.
• Treatment with an investigational drug within 28 days or 5 half-lives preceding the first dose of study treatment (whichever is longer).
• Abnormal BP, ECG and lab tests including AST/ALT, total bilirubin and anterior pituitary hormones, at screenings and/or baseline, based on pre-specified criteria per protocol.
• Unwilling or unable to comply with the Lifestyle guidance specified in this protocol (Lifestyle Considerations section).

Sponsors & Collaborators

• Pfizer: lead

Study Sites (7)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

First OC Dermatology

Fountain Valley, California, 92708, United States

Location

Keck School of Medicine of USC

Los Angeles, California, 90033, United States

Location

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Orange County Research Center

Tustin, California, 92780, United States

Location

Vital Prospects Clinical Research Institute, PC

Tulsa, Oklahoma, 74136, United States

Location

Aspen Clinical Research

Orem, Utah, 84058, United States

Location

Related Links

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

MeSH Terms

Conditions

Dermatitis, Atopic; Dermatitis

Condition Hierarchy (Ancestors)

Skin Diseases, Genetic; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases; Skin and Connective Tissue Diseases; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 16, 2020
• Study Start: December 10, 2020
• Primary Completion: December 27, 2022
• Study Completion: December 27, 2022
• Last Updated: June 3, 2024
• Results First Posted: June 3, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)