A Target Occupancy Study With Ritlecitinib.

AN OPEN LABEL, PHASE 1, TWO-ARM STUDY TO ASSESS TARGET OCCUPANCY AND FUNCTIONAL INHIBITION OF JAK3 AND TEC KINASES BY SINGLE DOSES OF RITLECITINIB IN HEALTHY ADULT PARTICIPANTS

This is a phase 1, open label, two-arm study to assess target occupancy and functional inhibition of JAK3 and TEC kinases by Ritlecitinib in healthy adult participants

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Ritlecitinib 50 mg; Drug: Ritlecitinib 200 mg

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Clinical Research Unit - New Haven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria apply:

• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination including BP and pulse rate measurement, 12-lead ECG, or clinical and laboratory tests.
• BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Infection with HIV, hepatitis B or hepatitis C viruses
• Have evidence of untreated or inadequately treated active or latent Mycobacterium TB infection
• Known active or history of recurrent bacterial, viral, fungal, mycobacterial or other infections.
• Have received only one of the 2 required doses of COVID-19 vaccine.
• Participants have a known present or a history of malignancy other than a successfully treated or excised non metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Subjects will be dosed with 50 mg Ritlecitinib on Day 1 and followed up till Day 3	Drug: Ritlecitinib 50 mg; 50 mg single dose; Other Names: PF-06651600
Experimental: Cohort 2; Subjects will be dosed with 200 mg Ritlecitinib on Day 1 and followed up till Day 3	Drug: Ritlecitinib 200 mg; 200 mg single dose; Other Names: PF-06651600

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Target Occupancy for JAK3	Target occupancy for janus kinase 3 (JAK3) in peripheral blood mononuclear cells (PBMCs) by ritlecitinib was investigated in human blood by chemical probe-based enrichment and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Percent Target Occupancy for BTK	Target occupancy for Bruton's tyrosine kinase (BTK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Percent Target Occupancy for ITK	Target occupancy forIL 2 inducible T-cell kinase (ITK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Percent Target Occupancy for TXK	Target occupancy for tyrosine kinase expressed in T cells (TXK) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Percent Target Occupancy for TEC	Target occupancy for tyrosine kinase expressed carcinoma (TEC) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point)*100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Percent Target Occupancy for BMX	Target occupancy for bone marrow tyrosine kinase gene in chromosome X (BMX) in PBMCs by ritlecitinib was investigated in human blood by chemical probe-based enrichment and LC-MS/MS analysis. % TO is calculated as [(baseline value - value at specified time point) *100/baseline value], where baseline value in this formula is defined as the mean of the two pre-dose measurements at Hour -1 and Hour 0 on Day 1. Since (baseline value - value at specified time point)=0 at baseline, % TO at baseline is 0.	-1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib	Cmax is maximum observed plasma concentration. Cmax for ritlecitinib was observed directly from data.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ritlecitinib	Tmax is time for Cmax. Tmax for ritlecitinib was observed directly from data as time of first occurrence.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Last Quantifiable Plasma Concentration (Clast) of Ritlecitinib	Clast is last quantifiable plasma concentration. Clast for ritlecitinib was observed directly from data.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Average Plasma Concentration From Time 0 to 24 Hours (Cav) of Ritlecitinib	Cav is average plasma concentration from time 0 to 24 hours over the 24 hours period. Cav for ritlecitinib was calculated as area under the plasma concentration-time curve from 0 to 24 hours (AUC24) divided by 24.	0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Ritlecitinib	AUClast is area under the plasma concentration-time profile from time 0 to the time of the Clast. AUClast for ritlecitinib was determined using linear/log trapezoidal method.	0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
Area Under the Curve From Time 0 to 24 Hours (AUC24) of Ritlecitinib	AUC24 is area under the plasma concentration-time curve from time 0 to 24 hours. AUC24 for ritlecitinib was determined using linear/log trapezoidal method.	0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose
Number of Participants With All-Causality and Treatment-Related Treatment-Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study treatment and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
Number of Participants With Treatment-Emergent Adverse Events by Severity	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. Treatment-emergent are events between first dose of study treatment and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs are classified according to the severity in 3 categories a) mild - AEs does not interfere with participant's usual function b) moderate - AEs interferes to some extent with participant's usual function c) severe - AEs interferes significantly with participant's usual function.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
Number of Participants With Laboratory Abnormalities Without Regard to Baseline Abnormality	Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocyte, platelet, neutrophils, eosinophils, monocytes, basophils, lymphocytes, etc), chemistry (glucose, calcium, sodium, potassium, chloride, total bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, protein, albumin, etc), and urinalysis (glucose, protein, hemoglobin, ketones, nitrite, leukocytes, urine bacteria, etc). Baseline = the pre-dose measurement on Day -1. Laboratory abnormalities meeting pre-defined criteria are reported for this outcome measure. Only those categories in which at least 1 participant had data were reported. ULN=upper limit of normal. LPF=low power field.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
Number of Participants With Pre-defined Criteria for Vital Signs	Pre-defined criteria included: 1) Diastolic blood pressure (DBP), a) supine DBP: less than (<) 50 mmHg, b) supine DBP: change of >= 20mmHg increase, c) supine DBP: change of >= 20mmHg decrease; 2) Systolic blood pressure (SBP), a) supine SBP: <90 mmHg, b) supine SBP: change of >=30mmHg increase, c) supine SBP: change of >=30mmHg decrease; 3) Supine pulse rate, a) <40 bpm, b) >120 bpm. mmHg=millimeters of mercury, bpm=beats per minute.	From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2021
• Primary Completion (Actual): January 14, 2022
• Study Completion (Actual): January 14, 2022

Study Registration Dates

• First Submitted: October 15, 2021
• First Submitted That Met QC Criteria: November 10, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: B7981045

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No