A Target Occupancy Study With Ritlecitinib.

November 9, 2023 updated by: Pfizer

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percent Target Occupancy for JAK3
Time Frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: -1 (pre-dose), 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib
Time Frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: 0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose
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
Time Frame: 0 (pre-dose), 1, 2, 4, 8, 24, 48 hours post-dose
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
Time Frame: 0 (pre-dose), 1, 2, 4, 8, 24 hours post-dose
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)
Time Frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
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
Time Frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
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
Time Frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
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
Time Frame: From the first dose of study treatment up to 35 days after the last dose of study treatment (up to 35 days)
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Pfizer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 22, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 14, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 14, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 10, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 19, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 13, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

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