Clinical Trial Results:
An Interventional PK, PD, Phase 1, Open-Label Study to Investigate PK and PD of Multiple-Dose Ritlecitinib in Children 6 to Less Than 12 Years of Age With Severe Alopecia Areata
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Summary
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EudraCT number |
2023-000824-12 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
11 Aug 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Jan 2024
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First version publication date |
28 Jan 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B7981031
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05650333 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Centre, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Centre, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-002451-PIP01-18 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Dec 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
11 Aug 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of the trial was to characterise the pharmacokinetics (PK) of Ritlectinib in subjects with alopecia areata (AA) 6 to less than (<) 12 years of age.
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trials subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Mar 2023
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
15
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
15
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
A total of 15 subjects were enrolled at 6 sites in the United States. Study started from 02 March 2023 and completed on 11 August 2023. | ||||||||||
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Period 1
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Period 1 title |
Treatment Period
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Ritlecitinib 20 mg | ||||||||||
Arm description |
Subjects received Ritlecitinib 20 milligram (mg) orally once daily (QD), for 7 consecutive days. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Ritlecitinib
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Investigational medicinal product code |
PF-06651600
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received Ritlecitinib 20 mg, orally QD, for 7 consecutive days.
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Period 2
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Period 2 title |
Follow-up Period
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Is this the baseline period? |
No | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Ritlecitinib 20 mg | ||||||||||
Arm description |
Subjects received Ritlecitinib 20 mg, orally QD, for 7 consecutive days. | ||||||||||
Arm type |
No intervention | ||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Ritlecitinib 20 mg
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Reporting group description |
Subjects received Ritlecitinib 20 milligram (mg) orally once daily (QD), for 7 consecutive days. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ritlecitinib 20 mg
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Reporting group description |
Subjects received Ritlecitinib 20 milligram (mg) orally once daily (QD), for 7 consecutive days. | ||
Reporting group title |
Ritlecitinib 20 mg
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Reporting group description |
Subjects received Ritlecitinib 20 mg, orally QD, for 7 consecutive days. | ||
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End point title |
Area Under the Plasma Concentration-Time Profile Over the Dosing Interval of 24 Hours, at Steady State (AUC24) of Ritlecitinib on Day 7 [1] | ||||||||
End point description |
Linear-log trapezoidal method was used for evaluation. The pharmacokinetic (PK) parameter analysis population included all subjects treated who had at least 1 of the PK parameters of primary interest. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint. Two subjects were not included in analysis because they did not have evaluable PK data.
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End point type |
Primary
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End point timeframe |
0 (pre-dose), 0.5, 1, 3, 8 and 24 hours post-dose on Day 7 [Pre-dose concentration was used as an estimate for the concentration of 24 hours post-dose]
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Statistical analysis was not planned for this endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Maximum Observed Plasma Concentration (Cmax) of Ritlecitinib | ||||||||
End point description |
The PK parameter analysis population included all subjects treated who had at least 1 of the PK parameters of primary interest. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint. Two subjects were not included in analysis because they did not have evaluable PK data.
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End point type |
Secondary
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End point timeframe |
0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Ritlecitinib | ||||||||
End point description |
The PK parameter analysis population included all subjects treated who had at least 1 of the PK parameters of primary interest. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint. Two subjects were not included in analysis because they did not have evaluable PK data.
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End point type |
Secondary
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End point timeframe |
0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Oral Clearance (CL/F) of Ritlecitinib | ||||||||
End point description |
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological process. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. The PK parameter analysis population included all subjects treated who had at least 1 of the PK parameters of primary interest. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint. Two subjects were not included in analysis because they did not have evaluable PK data.
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End point type |
Secondary
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End point timeframe |
0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7
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| No statistical analyses for this end point | |||||||||
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End point title |
Apparent Volume of Distribution (Vz/F) of Ritlecitinib | ||||||||
End point description |
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F is influenced by the fraction absorbed. The PK parameter analysis population included all subjects treated who had at least 1 of the PK parameters of primary interest. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint. Two subjects were not included in analysis because they did not have evaluable PK data.
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End point type |
Secondary
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End point timeframe |
0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7
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| No statistical analyses for this end point | |||||||||
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End point title |
Terminal Elimination Half-Life (t1/2) of Ritlecitinib | ||||||||
End point description |
The PK parameter analysis population included all subjects treated who had at least 1 of the PK parameters of primary interest. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint. Two subjects were not included in analysis because they did not have evaluable PK data.
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End point type |
Secondary
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End point timeframe |
0 (pre-dose), 0.5, 1, 3 and 8 hours post-dose on Day 7
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Interferon Gamma Induced Protein 10 (IP-10) on Day 7 | ||||||||||||
End point description |
The pharmacodynamic (PD) parameter analysis population included all subjects treated who had at least 1 of the PD parameters of primary interest. Here, “n” signifies number of subjects evaluable for specified rows.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 7
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in T Lymphocytes on Day 7 | ||||||||||||||||||||
End point description |
The PD parameter analysis population included all subjects treated who had at least 1 of the PD parameters of primary interest. T lymphocytes included CD3 cells, CD4 T helper lymphocytes and CD8 T cytotoxic lymphocytes. Here, “n” signifies number of subjects evaluable for specified rows.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 7
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Change From Baseline in B Lymphocytes on Day 7 | ||||||||||||
End point description |
The PD parameter analysis population included all subjects treated who had at least 1 of the PD parameters of primary interest. B lymphocytes included CD19 cells. Here, “n” signifies number of subjects evaluable for specified rows.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 7
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Natural Killer (NK) Cells on Day 7 | ||||||||||||
End point description |
The PD parameter analysis population included all subjects treated who had at least 1 of the PD parameters of primary interest. NK cells included CD3 (-), CD16 (+), CD56 (+) cells. Here, “n” signifies number of subjects evaluable for specified rows.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 7
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | ||||||
End point description |
An AE is any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Treatment-emergent were events between first dose to 35 days after last dose, that were absent before treatment or that worsened relative to pretreatment state. Safety analysis set included all subjects assigned to study intervention and who received at least 1 dose of study intervention. Subjects were analysed according to the product they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 of dosing up to 35 days after the last dose (Day 42)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Treatment Related AEs | ||||||
End point description |
Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Safety analysis set included all subjects assigned to study intervention and who received at least 1 dose of study intervention. Subjects were analysed according to the product they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 of dosing up to 35 days after the last dose (Day 42)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Serious AEs (SAEs) | ||||||
End point description |
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. Safety analysis set included all subjects assigned to study intervention and who received at least 1 dose of study intervention. Subjects were analysed according to the product they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 of dosing up to 35 days after the last dose (Day 42)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With AEs Leading to Treatment Discontinuation | ||||||
End point description |
Safety analysis set included all subjects assigned to study intervention and who received at least 1 dose of study intervention. Subjects were analysed according to the product they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 7
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Clinically Significant Abnormalities in Vital Signs | ||||||
End point description |
Vital Signs evaluation included blood pressure and heart rate measurements. Clinical significance was judged by investigator. Safety analysis set included all subjects assigned to study intervention and who received at least 1 dose of study intervention. Subjects were analysed according to the product they actually received.
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 7
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Clinically Significant Abnormalities in Clinical Laboratory Values | ||||||
End point description |
Clinical laboratory parameters included haematology: haemoglobin, haematocrit, red blood cells count, platelet count, white blood cells count, total absolute: neutrophils, eosinophils, monocytes, basophils, lymphocytes; chemistry: urea and creatinine estimated creatinine clearance, glucose (fasting), sodium, potassium, chloride, aspartate aminotransferase (AT), alanine AT, total bilirubin, alkaline phosphatase, albumin, total protein; urinalysis: local dipstick: pH, qualitative: glucose, protein, albuminuria, blood, ketones, nitrites, leukocyte esterase and others. Clinical significance was judged by investigator. Safety analysis set was evaluated.
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 7
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects as per Score for Paediatric Taste Assessment Questionnaire | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
The paediatric taste questionnaire included 3 questions regarding: 1) Overall Taste, 2) Overall Mouthfeel and 3) Overall Volume of Medicine. Each question ranged from 1 (most favourable) to 5 (least favourable). Safety analysis set included all subjects assigned to study intervention and who received at least 1 dose of study intervention. Subjects were analysed according to the product they actually received. Here, “Number of Subjects Analyzed” signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Day 1 and 7
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Day 1 up to 35 days after last dose (Day 42)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||
Dictionary version |
26.0
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Reporting groups
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Reporting group title |
Ritlecitinib 20 mg QD
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Reporting group description |
Subjects received Ritlecitinib 20 mg, orally QD, for 7 consecutive days. | ||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
