The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics of escalating single and repeat doses of PF-07832837 in healthy participants and in participants with moderate to severe atopic dermatitis. An additional goal is to assess the pharmacodynamics of PF-07832837 in participants with moderate to severe AD, including potential effects on clinical signs and symptoms
This is a first-in-human (FIH) study of PF-07832837 that will be conducted in 2 parts: Part 1 will be conducted in healthy adult participants and Part 2 will be conducted in adult participants with moderate to severe AD. Part 1 is within-cohort randomized, participant- and investigator-blind, sponsor-open, placebo-controlled investigation of the safety, tolerability, PK, and immunogenicity following single and multiple ascending doses of PF-07832837 in healthy participants. Part 1 may also include a cohort of Japanese healthy adult participants to provide safety, tolerability, and PK data in Japanese population to enable the inclusion of Japanese participants in future clinical trials. Part 2 is a randomized, participant- and investigator-blind, sponsor-open, placebo-controlled study to investigate the safety, tolerability, PK, and pharmacodynamics (including clinical effects) of PF-07832837 in participants with moderate to severe AD. Part 2 will consist of cohorts of participants with moderate to severe AD. A total of approximately 28 participants will receive either active PF-07832837 or placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
119
escalated doses of PF-07832837
placebo
Anaheim Clinical Trials, LLC
Anaheim, California, United States
RECRUITINGNumber of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and serious adverse events (SAEs) Following single ascending doses (SAD)
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.
Time frame: Baseline up to Day 35
Number of Participants with Clinically significant Laboratory Abnormalities Following SAD
Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Time frame: Baseline up to Day 35
Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings Following SAD
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. Clinically significant findings were determined by the investigator.
Time frame: Baseline up to Day 35
Number of Participants with Clinically Significant Change from Baseline in Vital Signs Following SAD
Vital signs included blood pressure, pulse rate, respiratory rate, oxygen saturation and oral temperature. Clinically significant findings were determined by the investigator.
Time frame: Baseline up to Day 35
Number of Participants with Clinically Significant Change from Baseline in Cardiac Telemetry Findings Following SAD
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Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.
Time frame: Day 1
Number of Participants With Treatment Emergent Treatment-Related AEs and SAEs Following multiple ascending doses (MAD)
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.
Time frame: Baseline up to Day 50
Number of Participants with Clinically significant Laboratory Abnormalities Following MAD
Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Time frame: Baseline up to Day 50
Number of Participants with Change from Baseline in Electrocardiogram (ECG) Findings Following MAD
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. Clinically significant findings were determined by the investigator.
Time frame: Baseline up to Day 50
Number of Participants With Treatment Emergent Treatment-Related AEs and SAEs in participants with atopic dermatitis (AD)
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.
Time frame: Baseline up to Day 80
Number of Participants with Clinically significant Laboratory Abnormalities in participants with AD
Number of participants with any laboratory test abnormalities meeting pre-defined criteria was reported in this outcome measure.
Time frame: Baseline up to Day 80
Number of Participants with Clinically Significant Change from Baseline in Vital Signs in participants with AD
Vital signs included blood pressure, pulse rate, respiratory rate, oxygen saturation and oral temperature. Clinically significant findings were determined by the investigator.
Time frame: Baseline up to Day 78
Area Under the Curve From Time Zero to Last (AUClast) of PF-07832837 following SAD
estimated by Linear/Log trapezoidal method
Time frame: Day 1 to Day 35
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-07832837 following SAD
AUClast + (Clast\*/kel), where Clast\* is the predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis
Time frame: Day 1 to Day 35
Maximum Observed Serum Concentration (Cmax) of PF-07832837 following SAD
Observed directly from data
Time frame: Day 1 to Day 35
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07832837 following SAD
Observed directly from data as time of first occurrence
Time frame: Day 1 to Day 35
Terminal serum elimination half life (t1/2) of PF-07832837 following SAD
Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the loglinear concentration time curve. Only those data points judged to describe the terminal log-linear decline will be used in the regression
Time frame: Day 1 to Day 35
Area Under the Serum Concentration-Time Curve Over the Dosing Interval (AUCtau) of PF-07832837 following MAD
Linear/log trapezoidal method
Time frame: Day 1 to Day 22
Maximum Observed Serum Concentration (Cmax) of PF-07832837 following MAD
Observed directly from data
Time frame: Day 1 to Day 22
Time to Reach Maximum Observed Serum Concentration (Tmax) of PF-07832837 following MAD
Observed directly from data as the time of first occurrence
Time frame: Day 1 to Day 22
Percent change from baseline in Eczema Area and Severity Index (EASI) total score at Week 8
EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \<70%), 5 (70 to \<90%) and 6 (90 to 100%). Total EASI score =0.1\*Ah\*(Eh+Ih+Exh+Lh) + 0.2\*Au\*(Eu+Iu+ExU+Lu) + 0.3\*At\*(Et+It+Ext+Lt) + 0.4\*Al\*(El+Il+Exl+Ll); A = EASI area score; E = erythema; I = induration/papulation; Ex = excoriation; L = lichenification; h = head and neck; u = upper limbs; t = trunk; l = lower limbs. Total EASI score ranged from 0.0 to 72.0, higher scores = greater severity of AD.
Time frame: Baseline, Week 8