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Clinical Trial Results:
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of JTE-451 Administered for 16 Weeks in Subjects with Moderate to Severe Plaque Psoriasis (IMPACT-PS)

Summary
EudraCT number	2018-003359-40
Trial protocol	PL
Global end of trial date	13 Mar 2020

Results information
Results version number	v1(current)
This version publication date	20 Mar 2021
First version publication date	20 Mar 2021
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

AE451-G-18-004

ISRCTN number

US NCT number

NCT03832738

WHO universal trial number (UTN)

Other trial identifiers

IND Number: 129963

Sponsor organisation name

Akros Pharma Inc.

Sponsor organisation address

302 Carnegie Center, Suite 300, Princeton, United States, NJ 08540

Public contact

Kala Patel, Akros Pharma Inc., patel@akrospharma.com

Scientific contact

Kala Patel, Akros Pharma Inc., patel@akrospharma.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

20 Apr 2020

Is this the analysis of the primary completion data?

Yes

Primary completion date

13 Mar 2020

Global end of trial reached?

Yes

Global end of trial date

13 Mar 2020

Was the trial ended prematurely?

Main objective of the trial

This was a Phase-2, multicentre, double-blind, placebo-controlled 16-week study. The primary objective of this study was to evaluate the efficacy of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis compared with placebo. The secondary objectives of the study were to evaluate the safety, tolerability and pharmacokinetics (PK) of JTE-451 administered for 16 weeks in subjects with moderate to severe plaque psoriasis.

Protection of trial subjects

The study was conducted in compliance with the protocol, Good Clinical Practice and applicable regulatory requirement(s) (e.g., 21 Code of Federal Regulations Parts 50, 56, 312 in the United States), Sponsor/designee policies and procedures, and all applicable local and national clinical trial regulations. From a safety perspective, appropriate study restrictions based on the mechanism of action (MOA) of JTE-451 (i.e., selective immunomodulatory effect) were implemented including screening procedures and exclusion criteria to mitigate and minimise the risk of infections as well as tuberculosis and viral infections were included to ensure the safety of subjects. Each subject signed an informed consent form (ICF) containing appropriate trial and study drug information and was provided a copy of the ICF. The subjects at high risk of developing immunosuppression-related adverse events (AEs), such as infections or malignancies, including those with pre-existing conditions (e.g., clinically-manifested or active tubercle bacillus (TB)/untreated latent TB, active infections with hepatitis B virus, hepatitis C virus or human immunodeficiency virus or significant haematological condition were excluded from participating in the study. Other general safety-related restrictions such as cardiovascular-system-related, hepatic, and renal function-related restrictions, as well as the known safety signals associated with other compounds with similar MOA, were implemented to monitor and adequately manage safety-related findings.

Background therapy

Evidence for comparator

Actual start date of recruitment

17 Jan 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 124

Country: Number of subjects enrolled

United States: 15

Country: Number of subjects enrolled

Canada: 13

Worldwide total number of subjects

152

EEA total number of subjects

124

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

139

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Eligible subjects were randomised at Visit 2 to receive JTE-451 200 mg twice daily (BID; 400 mg/day), 400 mg BID (800 mg/day), or placebo BID for 16 weeks. Randomisation was stratified based on prior exposure of subjects to biologic therapy (biologic-naïve versus [vs.] biologic-experienced) and body weight (<90 kg vs. ≥90 kg at Visit 2).

Screening details

Study duration was approximately 24 weeks per subject as follows: • Screening period: Day -28 (Visit 1) to Day 1 (Visit 2/Randomisation Visit) • 16-week double-blind treatment period: Day 1 (Visit 2) to Day 112±4 (Visit 7/Week 16) • Up to 4-week follow-up period: Day 112±4 (Visit 7/Week 16) to Day 140±4 (Visit 8/Week 20)

Period 1 title

Treatment Period (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Blinding implementation details

The treatment assigned to each subject was not disclosed to the Sponsor members or designees involved in the study, study staff at the site or to the subject. JTE-451 200 mg tablets as well as placebo tablets were supplied as unbranded tablets, which were identical in appearance.

Are arms mutually exclusive

Yes

JTE-451 200 mg BID

Arm description

The subjects received a total daily dose of 400 mg of JTE-451.

Arm type

Experimental

Investigational medicinal product name

JTE-451 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

During the treatment period, the subjects self-administered 2 oral doses (2 tablets [1 tablet of JTE-451 200 mg and 1 placebo tablet]/dose, BID at approximately 12-hour intervals, regardless of meals) on Day 1 and daily up to Week 16. Each JTE-451 tablet contained 200 mg of JTE-451 and inactive ingredients. Each placebo tablet contained the same inactive ingredients as JTE-451 200 mg tablet except the active drug (JTE-451).

JTE-451 400 mg BID

Arm description

The subjects received a total daily dose of 800 mg of JTE-451.

Arm type

Experimental

Investigational medicinal product name

JTE-451 200 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

During the treatment period, the subjects self-administered 2 oral doses (2 tablets of JTE-451 200 mg/dose, BID at approximately 12-hour intervals, regardless of meals) on Day 1 and daily up to Week 16. Each JTE-451 tablet contained 200 mg of JTE-451 and inactive ingredients.

Placebo

Arm description

The subjects received a placebo-treatment.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

During the treatment period, the subjects self-administered 2 oral doses (2 placebo tablets/dose, BID at approximately 12-hour intervals, regardless of meals) on Day 1 and daily up to Week 16. Each placebo tablet contained the same inactive ingredients as JTE-451 200 mg tablet except the active drug (JTE-451).

Number of subjects in period 1	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Started	51	50	51
Completed	43	38	32
Not completed	8	12	19
Consent withdrawn by subject	6	7	16
Physician decision	-	1	2
Adverse event, non-fatal	2	3	1
Pregnancy	-	1	-

Baseline characteristics

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Reporting group title

JTE-451 200 mg BID

Reporting group description

The subjects received a total daily dose of 400 mg of JTE-451.

Reporting group title

JTE-451 400 mg BID

Reporting group description

The subjects received a total daily dose of 800 mg of JTE-451.

Reporting group title

Placebo

Reporting group description

The subjects received a placebo-treatment.

Reporting group values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo	Total
Number of subjects	51	50	51	152
Age categorical
Demographic details analysed for Intent-to-Treat (ITT) population are presented here. The ITT population consisted of all subjects who were randomised at Visit 2.
Units: Subjects
Adults (18-64 years)	47	46	46	139
From 65-84 years	4	4	5	13
Age continuous
Units: years
arithmetic mean (standard deviation)	45.7 ( 12.33 )	45.5 ( 13.96 )	44.5 ( 13.08 )	-
Gender categorical
Units: Subjects
Female	13	21	16	50
Male	38	29	35	102
Weight category at randomisation
Units: Subjects
<90 kg	25	24	25	74
≥90 kg	26	26	26	78
Screening body mass index
Units: kilogram(s)/square meter
arithmetic mean (standard deviation)	28.843 ( 5.1080 )	29.828 ( 5.2058 )	29.519 ( 4.1446 )	-

End points

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Reporting group title

JTE-451 200 mg BID

Reporting group description

The subjects received a total daily dose of 400 mg of JTE-451.

Reporting group title

JTE-451 400 mg BID

Reporting group description

The subjects received a total daily dose of 800 mg of JTE-451.

Reporting group title

Placebo

Reporting group description

The subjects received a placebo-treatment.

Subject analysis set title

JTE-451 200 mg BID - PK Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The PK population consisted of the randomised subjects who received at least one dose of JTE-451 and had at least one usable JTE-451 plasma concentration measurement. In JTE-451 200 mg BID - PK Population, the numbers of subjects analysed were 49 at Week 0 (pre-dose), 45 at Week 4 (pre-dose), 41 at Week 8 (pre-dose), 42 at Week 12 (pre-dose), and 42 at Week 16 (trough).

Subject analysis set title

JTE-451 400 mg BID - PK Population

Subject analysis set type

Sub-group analysis

Subject analysis set description

The PK population consisted of the randomised subjects who received at least one dose of JTE-451 and had at least one usable JTE-451 plasma concentration measurement. In JTE-451 400 mg BID - PK Population, the numbers of subjects analysed were 47 at Week 0 (pre-dose), 43 at Week 4 (pre-dose), 39 at Week 8 (pre-dose), 36 at Week 12 (pre-dose), and 33 at Week 16 (trough).

Primary: Proportion of subjects who achieved psoriasis area and severity index (PASI)-75 response rate at end of treatment (EOT) in the ITT population

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End point title

Proportion of subjects who achieved psoriasis area and severity index (PASI)-75 response rate at end of treatment (EOT) in the ITT population

End point description

The PASI quantifies the severity of a subject's psoriasis based on both, "lesion severity" and the "percent of body surface area (BSA)" affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI-75 response rate was defined as at least 75 percent (%) reduction in PASI score relative to Baseline.

End point type

Primary

End point timeframe

EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	51
Units: number of subjects	6	11	4

Analysis of PASI-75 response rate at EOT

Comparison groups

JTE-451 200 mg BID v Placebo

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.558 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

0.39

upper limit

5.8

Notes
[1] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Analysis of PASI-75 response rate at EOT

Comparison groups

JTE-451 400 mg BID v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.035 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

3.74

Confidence interval

level

95%

sides

2-sided

lower limit

1.07

upper limit

13.1

Notes
[2] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Secondary: Proportion of subjects who achieved PASI-50 response rate at EOT in the ITT population

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End point title

Proportion of subjects who achieved PASI-50 response rate at EOT in the ITT population

End point description

The PASI quantifies the severity of a subject's psoriasis based on both, "lesion severity" and the "percent of BSA" affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI-50 response rate was defined as at least 50% reduction in PASI score relative to Baseline.

End point type

Secondary

End point timeframe

EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	51
Units: number of subjects	17	21	9

Analysis of PASI-50 response rate at EOT

Comparison groups

JTE-451 200 mg BID v Placebo

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.086 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

0.89

upper limit

5.75

Notes
[3] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Analysis of PASI-50 response rate at EOT

Comparison groups

JTE-451 400 mg BID v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006 ^[4]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

3.76

Confidence interval

level

95%

sides

2-sided

lower limit

1.45

upper limit

9.75

Notes
[4] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Secondary: Proportion of subjects who achieved PASI-90 response rate at EOT in the ITT population

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End point title

Proportion of subjects who achieved PASI-90 response rate at EOT in the ITT population

End point description

The PASI quantifies the severity of a subject's psoriasis based on both, "lesion severity" and the "percent of BSA" affected. PASI is a composite scoring by the investigator of degree of erythema, induration, and scaling (each scored separately) for each of 4 body regions (head and neck, upper limbs, trunk [including axillae and groin], and lower limbs [including buttocks]), with adjustment for the percent of BSA involved for each body region and for the proportion of the body region to the whole body. The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores representing greater severity of psoriasis. PASI-90 response rate was defined as at least 90% reduction in PASI score relative to Baseline.

End point type

Secondary

End point timeframe

EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	51
Units: number of subjects	1	3	1

Analysis of PASI-90 response rate at EOT

Comparison groups

Placebo v JTE-451 200 mg BID

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

superiority

P-value

> 0.999 ^[5]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

17.25

Notes
[5] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Analysis of PASI-90 response rate at EOT

Comparison groups

JTE-451 400 mg BID v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.244 ^[6]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

3.86

Confidence interval

level

95%

sides

2-sided

lower limit

0.36

upper limit

41.2

Notes
[6] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Secondary: Percent change from baseline in PASI score at EOT in the ITT population

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End point title

Percent change from baseline in PASI score at EOT in the ITT population

End point description

Combined assessment of lesion severity and area affected into single score; range=0 (no disease) to 72 (maximal disease). Body divided into 4 sections=head, upper/lower limbs, trunk; each area scored by itself and scores combined for final PASI. For each section, percent area of skin involved was estimated: 0 (0%) to 6 (90-100%) and severity estimated by clinical signs of erythema, induration, scaling; ranged 0-4: 0=none, 1=slight, 2=moderate, 3=marked, 4=very marked. Final PASI=sum of severity parameters for each section*area score*weighing factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4); total possible score range: 0=no disease to 72=maximal disease.

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: percent
arithmetic mean (standard deviation)	-30.33 ( 40.971 )	-37.89 ( 37.896 )	-17.53 ( 34.701 )

No statistical analyses for this end point

Secondary: Proportion of subjects who achieved Static Physician’s Global Assessment (sPGA) score of 0 or 1 at EOT in the ITT population

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End point title

Proportion of subjects who achieved Static Physician’s Global Assessment (sPGA) score of 0 or 1 at EOT in the ITT population

End point description

The sPGA of psoriasis is scored on a 5-point scale, reflecting a global consideration of the erythema, induration, and scaling across all psoriatic lesions. Average erythema, induration, and scaling are scored separately over the whole body according to a 5-point severity scale (0 [no symptom] to 4 [severe symptom]). The total score was calculated as average of the 3 severity scores and rounded to the nearest whole number score to determine the sPGA score and category (0=cleared; 1=minimal; 2=mild; 3=moderate; and 4=severe). sPGA response was defined as 0 (clear) or 1 (minimal).

End point type

Secondary

End point timeframe

EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	51
Units: number of subjects	13	14	3

Analysis of subjects with sPGA score 0 or 1 at EOT

Comparison groups

JTE-451 200 mg BID v Placebo

Number of subjects included in analysis

102

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.009 ^[7]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

5.21

Confidence interval

level

95%

sides

2-sided

lower limit

1.38

upper limit

19.62

Notes
[7] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Analysis of subjects with sPGA score 0 or 1 at EOT

Comparison groups

JTE-451 400 mg BID v Placebo

Number of subjects included in analysis

101

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002 ^[8]

Method

Cochran-Mantel-Haenszel

Parameter type

Odds ratio (OR)

Point estimate

7.35

Confidence interval

level

95%

sides

2-sided

lower limit

1.86

upper limit

29.08

Notes
[8] - The p-value was estimated based on Cochran-Mantel-Haenszel test stratified by prior exposure to biologic therapy (Yes/No) and body weight (<90 kg/≥90 kg).

Secondary: Change from baseline in sPGA score at EOT in the ITT population

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End point title

Change from baseline in sPGA score at EOT in the ITT population

End point description

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: units on scale
arithmetic mean (standard deviation)	-0.96 ( 0.848 )	-1.02 ( 0.869 )	-0.54 ( 0.713 )

No statistical analyses for this end point

Secondary: Percent change from baseline in psoriasis BSA at EOT in the ITT population

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End point title

Percent change from baseline in psoriasis BSA at EOT in the ITT population

End point description

The total BSA affected by plaque-type psoriasis was estimated from the percentages of areas affected, including head, trunk, upper limbs and lower limbs. Each reported percentage was multiplied by its respective body region corresponding factor (head=0.1, upper limbs=0.2, trunk=0.3, lower limbs=0.4) and the resulting 4 values were added up to estimate the total BSA affected by plaque-type psoriasis.

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: percent
arithmetic mean (standard deviation)	-18.67 ( 39.582 )	-19.03 ( 48.696 )	-5.74 ( 38.707 )

No statistical analyses for this end point

Secondary: Change from baseline in Skindex-16 Overall Score at EOT in the ITT population

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End point title

Change from baseline in Skindex-16 Overall Score at EOT in the ITT population

End point description

Skindex-16 questionnaire contains 16 questions related to quality of life in subjects with skin disease. It consists of a short 16-item assessment completed by the subject, with each item rated on a 7-point Likert scale (0=never bothered to 6=always bothered). Responses to the Skindex-16 are categorised into three subscales: symptom, emotional, and functional; and their respective scores are expressed in a linear scale from 0 (no effect) to 100 (effect experienced all the time). Overall scale score is an average of 16 items.

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: units on scale
arithmetic mean (standard deviation)	-10.029 ( 23.2635 )	-10.896 ( 26.7910 )	-3.386 ( 20.8617 )

No statistical analyses for this end point

Secondary: Change from baseline in Skindex-16 Symptom Scale Scores at EOT in the ITT population

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End point title

Change from baseline in Skindex-16 Symptom Scale Scores at EOT in the ITT population

End point description

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: units on scale
arithmetic mean (standard deviation)	-8.905 ( 34.2989 )	-11.500 ( 31.5148 )	-2.170 ( 26.0563 )

No statistical analyses for this end point

Secondary: Change from baseline in Skindex-16 Emotions Scale Scores at EOT in the ITT population

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End point title

Change from baseline in Skindex-16 Emotions Scale Scores at EOT in the ITT population

End point description

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: units on scale
arithmetic mean (standard deviation)	-10.411 ( 21.8268 )	-13.143 ( 28.4467 )	-5.953 ( 22.6358 )

No statistical analyses for this end point

Secondary: Change from baseline in Skindex-16 Functioning Scale Scores at EOT in the ITT population

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End point title

Change from baseline in Skindex-16 Functioning Scale Scores at EOT in the ITT population

End point description

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	51	50	48
Units: units on scale
arithmetic mean (standard deviation)	-10.392 ( 23.5294 )	-7.267 ( 27.6823 )	-0.764 ( 20.1090 )

No statistical analyses for this end point

Secondary: Change from baseline in weekly average of Itch Numeric Rating Scale (NRS) at EOT in the ITT population

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End point title

Change from baseline in weekly average of Itch Numeric Rating Scale (NRS) at EOT in the ITT population

End point description

The Itch NRS is a validated, self-reported, instrument for measurement of itch intensity and subjects were asked to rate the intensity of their itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable); higher scores indicated greater itch intensity. The Itch NRS scores were recorded by the subject using the e-diary once daily from screening through the last visit.

End point type

Secondary

End point timeframe

Baseline and EOT

End point values	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Number of subjects analysed	50	50	48
Units: units on scale
arithmetic mean (standard deviation)	-1.302 ( 2.8165 )	-1.537 ( 3.2634 )	-0.547 ( 2.4239 )

No statistical analyses for this end point

Secondary: Trough plasma concentrations of JTE-451 in the PK population

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End point title

Trough plasma concentrations of JTE-451 in the PK population

End point description

Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]). Blood samples were collected at specific timepoints to measure trough plasma concentration of JTE-451 in the PK population.

End point type

Secondary

End point timeframe

Week 0 (pre-dose), Week 4 (pre-dose), Week 8 (pre-dose), Week 12 (pre-dose), and Week 16 (trough)

End point values	JTE-451 200 mg BID - PK Population	JTE-451 400 mg BID - PK Population
Number of subjects analysed	51 ^[9]	50 ^[10]
Units: nanogram per millilitre (ng/mL)
arithmetic mean (standard deviation)
Week 0 (pre-dose)	0 ( 0 )	0 ( 0 )
Week 4 (pre-dose)	444 ( 581 )	687 ( 602 )
Week 8 (pre-dose)	388 ( 439 )	751 ( 1490 )
Week 12 (pre-dose)	355 ( 271 )	876 ( 1480 )
Week 16 (trough)	575 ( 704 )	1210 ( 1660 )

Notes
[9] - Analysis set description provides the details for the number of subjects analysed at each timepoint.
[10] - Analysis set description provides the details for the number of subjects analysed at each timepoint.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

AEs occurring (initial occurrence or a worsening of a pre-existing condition) after the informed consent was signed and up to 4 weeks (28 days) after the last dose of study treatment were reported.

Adverse event reporting additional description

The treatment-emergent AEs (AEs that occurred during the treatment period or the follow-up period) are presented here for the safety population. The safety population consisted of the randomised subjects who received at least one dose of the study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

JTE-451 200 mg BID

Reporting group description

The subjects received a total daily dose of 400 mg of JTE-451.

Reporting group title

JTE-451 400 mg BID

Reporting group description

The subjects received a total daily dose of 800 mg of JTE-451.

Reporting group title

Placebo

Reporting group description

The subjects received a placebo-treatment.

Serious adverse events	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 51 (1.96%)	2 / 50 (4.00%)	1 / 50 (2.00%)
number of deaths (all causes)	0	0	0
number of deaths resulting from adverse events	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 51 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Psoriasis
subjects affected / exposed	0 / 51 (0.00%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Infections and infestations
Breast abscess
subjects affected / exposed	1 / 51 (1.96%)	0 / 50 (0.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 51 (0.00%)	1 / 50 (2.00%)	0 / 50 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 3%

Non-serious adverse events	JTE-451 200 mg BID	JTE-451 400 mg BID	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	20 / 51 (39.22%)	22 / 50 (44.00%)	17 / 50 (34.00%)
Investigations
Alanine aminotransferase increased
subjects affected / exposed	1 / 51 (1.96%)	3 / 50 (6.00%)	1 / 50 (2.00%)
occurrences all number	1	3	1
Blood glucose increased
subjects affected / exposed	2 / 51 (3.92%)	1 / 50 (2.00%)	2 / 50 (4.00%)
occurrences all number	2	1	2
Gamma-glutamyltransferase increased
subjects affected / exposed	2 / 51 (3.92%)	2 / 50 (4.00%)	0 / 50 (0.00%)
occurrences all number	2	2	0
Vascular disorders
Hypertension
subjects affected / exposed	2 / 51 (3.92%)	0 / 50 (0.00%)	1 / 50 (2.00%)
occurrences all number	3	0	1
Nervous system disorders
Headache
subjects affected / exposed	4 / 51 (7.84%)	1 / 50 (2.00%)	2 / 50 (4.00%)
occurrences all number	8	1	2
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 51 (3.92%)	2 / 50 (4.00%)	1 / 50 (2.00%)
occurrences all number	2	2	1
Abdominal pain upper
subjects affected / exposed	4 / 51 (7.84%)	2 / 50 (4.00%)	0 / 50 (0.00%)
occurrences all number	4	3	0
Diarrhoea
subjects affected / exposed	7 / 51 (13.73%)	19 / 50 (38.00%)	3 / 50 (6.00%)
occurrences all number	13	30	3
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	0 / 51 (0.00%)	0 / 50 (0.00%)	2 / 50 (4.00%)
occurrences all number	0	0	2
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	1 / 51 (1.96%)	2 / 50 (4.00%)	1 / 50 (2.00%)
occurrences all number	1	4	1
Infections and infestations
Nasopharyngitis
subjects affected / exposed	3 / 51 (5.88%)	2 / 50 (4.00%)	5 / 50 (10.00%)
occurrences all number	4	2	5
Pharyngitis
subjects affected / exposed	1 / 51 (1.96%)	0 / 50 (0.00%)	2 / 50 (4.00%)
occurrences all number	1	0	2
Sinusitis
subjects affected / exposed	0 / 51 (0.00%)	0 / 50 (0.00%)	2 / 50 (4.00%)
occurrences all number	0	0	2
Upper respiratory tract infection
subjects affected / exposed	2 / 51 (3.92%)	3 / 50 (6.00%)	4 / 50 (8.00%)
occurrences all number	2	3	4
Urinary tract infection
subjects affected / exposed	3 / 51 (5.88%)	3 / 50 (6.00%)	0 / 50 (0.00%)
occurrences all number	4	3	0

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of JTE-451 Administered for 16 Weeks in Subjects with Moderate to Severe Plaque Psoriasis (IMPACT-PS)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Proportion of subjects who achieved psoriasis area and severity index (PASI)-75 response rate at end of treatment (EOT) in the ITT population

Primary: Proportion of subjects who achieved psoriasis area and severity index (PASI)-75 response rate at end of treatment (EOT) in the ITT population

Secondary: Proportion of subjects who achieved PASI-50 response rate at EOT in the ITT population

Secondary: Proportion of subjects who achieved PASI-50 response rate at EOT in the ITT population

Secondary: Proportion of subjects who achieved PASI-90 response rate at EOT in the ITT population

Secondary: Proportion of subjects who achieved PASI-90 response rate at EOT in the ITT population

Secondary: Percent change from baseline in PASI score at EOT in the ITT population

Secondary: Percent change from baseline in PASI score at EOT in the ITT population

Secondary: Proportion of subjects who achieved Static Physician’s Global Assessment (sPGA) score of 0 or 1 at EOT in the ITT population

Secondary: Proportion of subjects who achieved Static Physician’s Global Assessment (sPGA) score of 0 or 1 at EOT in the ITT population

Secondary: Change from baseline in sPGA score at EOT in the ITT population

Secondary: Change from baseline in sPGA score at EOT in the ITT population

Secondary: Percent change from baseline in psoriasis BSA at EOT in the ITT population

Secondary: Percent change from baseline in psoriasis BSA at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Overall Score at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Overall Score at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Symptom Scale Scores at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Symptom Scale Scores at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Emotions Scale Scores at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Emotions Scale Scores at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Functioning Scale Scores at EOT in the ITT population

Secondary: Change from baseline in Skindex-16 Functioning Scale Scores at EOT in the ITT population

Secondary: Change from baseline in weekly average of Itch Numeric Rating Scale (NRS) at EOT in the ITT population

Secondary: Change from baseline in weekly average of Itch Numeric Rating Scale (NRS) at EOT in the ITT population

Secondary: Trough plasma concentrations of JTE-451 in the PK population

Secondary: Trough plasma concentrations of JTE-451 in the PK population

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of JTE-451 Administered for 16 Weeks in Subjects with Moderate to Severe Plaque Psoriasis (IMPACT-PS)