Study to Evaluate Safety and Tolerability of PF-07242813 in Healthy Participants and Participants With Atopic Dermatitis
- Conditions
- Atopic Dermatitis
- Interventions
- Drug: PF-07242813Drug: Placebo
- Registration Number
- NCT04668066
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 121
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Single ascending doses of PF-07242813 or placebo in healthy participants PF-07242813 Participants will receive a single intravenous dose of either PF-07242813 or placebo Single ascending doses of PF-07242813 or placebo in healthy participants Placebo Participants will receive a single intravenous dose of either PF-07242813 or placebo Multiple ascending doses of PF-07242813 or placebo in healthy participants PF-07242813 Participants will receive multiple subcutaneous doses PF-07242813 or placebo Multiple ascending doses of PF-07242813 or placebo in healthy participants Placebo Participants will receive multiple subcutaneous doses PF-07242813 or placebo Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis PF-07242813 Participants will receive a single intravenous dose of either PF-07242813 or placebo Single dose of PF-07242813 or placebo in participants with moderate to severe atopic dermatitis Placebo Participants will receive a single intravenous dose of either PF-07242813 or placebo
- Primary Outcome Measures
Name Time Method Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs From start of study treatment on Day 1 to Day 99 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.
Part 1: SAD Cohorts: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) From start of study treatment on Day 1 to Day 71 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.
Part 1: MAD Cohorts: Number of Participants With TEAEs and TESAEs From start of study treatment on Day 1 to Day 99 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.
Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Vital Signs From initiation of treatment to day 71 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.
Part 1: MAD Cohorts: Number of Participants With Laboratory Test Abnormalities Baseline (last pre-dose measurement) to Day 99 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.
Part 2: Number of Participants With TEAEs and TESAEs From start of study treatment on Day 1 to Week 16 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.
Part 2: Number of Participants With Clinically Significant Findings in Vital Signs From start of study treatment on Day 1 to Week 16 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.
Part 1: SAD Cohorts: Number of Participants With Laboratory Test Abnormalities Baseline (last pre-dose measurement) to Day 71 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.
Part 2: Number of Participants With Laboratory Test Abnormalities Baseline (last pre-dose measurement) to Week 16 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.
Part 1: SAD Cohorts Only: Number of Participants With Cardiac Telemetry Abnormalities From pre-dose up to 6 hours post dose on Day 1 Cardiac telemetry was collected in Part 1 SAD cohorts only. Number of participants with any cardiac telemetry abnormalities were reported in this outcome measure.
Part 1: SAD Cohorts: Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) From pre-dose on Day 1 up to Day 71 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.
Part 1: MAD Cohorts: Number of Participants With Clinically Significant Findings in ECG From pre-dose on Day 1 up to Day 99 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.
Part 2: Number of Participants With Clinically Significant Findings in ECG From pre-dose on week 1 to week 16 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.
- Secondary Outcome Measures
Name Time Method 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 AUCinf was determined as AUClast + (Clast divided by kel), where Clast = predicted serum concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel= terminal phase rate constant.
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 t1/2 was determined by "Loge(2)/kel", where kel was the terminal phase rate constant calculated by a linear regression of the loglinear -concentration time- curve.
Part 2: Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 6 Baseline, Week 6 EASI quantifies severity of AD based on severity of lesion clinical signs and percentage (%) of body surface area (BSA) affected. Severity of clinical signs of AD lesions (erythema, induration/papulation, excoriation and lichenification) were scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on a 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based on % 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, with higher scores indicating greater severity of AD.
Part 1: MAD Cohorts: Area Under the Serum Concentration Time Profile Over the Dosing Interval (AUCtau) for PF-07242813 Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) Area under the serum concentration time- profile over the dosing interval tau where tau=2 weeks (336 hours).
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 AUClast was calculated using the linear/log trapezoidal method.
Part 1: MAD Cohorts: Cmax for PF-07242813 Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) Part 1: MAD Cohorts: Tmax for PF-07242813 Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) Part 1: MAD Cohorts: Terminal Elimination Half Life (t1/2) for PF-07242813 Day 1,15,29(Pre-dose,2,6,12,24,48,72,96 hours post-dose) Day 15,29(168hours post-dose) Day 29(336,672,1008,1344,1680hours post-dose) (For all cohorts); Day 1(168hours post-dose for all except 15mg and 50 mg post-dose) t1/2 was determined by "Loge(2) per kel", where kel was the terminal phase rate constant calculated by a linear regression of the log/linear -concentration time- curve.
Trial Locations
- Locations (7)
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
First OC Dermatology
🇺🇸Fountain Valley, California, United States
Keck School of Medicine of USC
🇺🇸Los Angeles, California, United States
Orange County Research Center
🇺🇸Tustin, California, United States
Aspen Clinical Research
🇺🇸Orem, Utah, United States
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Vital Prospects Clinical Research Institute, PC
🇺🇸Tulsa, Oklahoma, United States