NCT03575871: JADE Mono-2

Study Evaluating Efficacy and Safety of PF-04965842 in Subjects Aged 12 Years And Older With Moderate to Severe Atopic Dermatitis

Completed Phase 3 Results posted Last updated 21 April 2020

What this trial tests

Phase 3 trial testing PF-04965842 100 mg in Dermatitis, Atopic in 391 participants. Completed in 13 August 2019.

Timeline

29 June 2018

Primary endpoint
13 August 2019

13 August 2019

Quick facts

Lead sponsor	Pfizer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	391
Start date	29 June 2018
Primary completion	13 August 2019
Estimated completion	13 August 2019
Sites	115 locations across Japan, United Kingdom, Germany, Hungary, Poland, South Korea, Canada, Bulgaria

Drugs / interventions tested

• PF-04965842 100 mg — full drug profile →
• PF-04965842 200 mg — full drug profile →
• Placebo

Conditions studied

• Dermatitis, Atopic — all drugs for Dermatitis, Atopic →

Sponsor

Pfizer — full company profile →

Who can join

12 and older, any sex, with Dermatitis, Atopic. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) or Almost Clear (1) and Greater Than or Equal to (>=) 2 Points Improvement From Baseline at Week 12 Primary · Baseline, Week 12

IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriati

Group	Value	95% CI
PF-04965842 100 mg	28.4	21.3 – 35.5
PF-04965842 200 mg	38.1	30.4 – 45.7
Placebo	9.1	2.7 – 15.5

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75 Percent (%) Improvement (EASI-75) From Baseline at Week 12 Primary · Baseline, Week 12

EASI evaluates severity of participants AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\] on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to \

Group	Value	95% CI
PF-04965842 100 mg	44.5	36.7 – 52.3
PF-04965842 200 mg	61.0	53.3 – 68.7
Placebo	10.4	3.6 – 17.2

Percentage of Participants Who Achieved at Least 4-Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8 and 12

Participants were asked to assess their worst pruritus/itching due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst possible itching), where higher scores indicated greater severity.

Week 2

Group	Value	95% CI
PF-04965842 100 mg	23.1	16.5 – 29.7
PF-04965842 200 mg	35.3	27.7 – 42.9
Placebo	3.9	0.0 – 8.3

Week 4

Group	Value	95% CI
PF-04965842 100 mg	31.4	24.1 – 38.7
PF-04965842 200 mg	50.3	42.4 – 58.2
Placebo	3.9	0.0 – 8.3

Week 8

Group	Value	95% CI
PF-04965842 100 mg	39.1	31.4 – 46.8
PF-04965842 200 mg	51.6	43.7 – 59.6
Placebo	11.8	4.6 – 19.1

Week 12

Group	Value	95% CI
PF-04965842 100 mg	39.7	32.1 – 47.4
PF-04965842 200 mg	49.0	41.1 – 56.9
Placebo	10.5	3.6 – 17.4

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 12 Secondary · Baseline, Week 12

PSAAD is a daily participant reported symptom electronic diary. Participants rated their symptoms of AD over the past 24 hours, using 11 items (itchy skin, painful skin, dry skin, flaky skin, cracked skin, bumpy skin, red skin, discolored skin \[lighter or darker\], bleeding from skin, seeping or oozing fluid from skin \[other than blood\], and skin swelling). Participant had to think about all the areas of their body affected by their skin condition and chose the number that best described their experience for each of the 11 items, from 0 (no symptoms) to 10 (extreme symptoms), higher scores

Group	Value	95% CI
PF-04965842 100 mg	-2.4	-2.8 – -2.1
PF-04965842 200 mg	-3.0	-3.3 – -2.7
Placebo	-0.8	-1.3 – -0.3

Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale (NRS) for Severity of Pruritus Secondary · Baseline up to Day 15

Participants were asked to assess their worst itching/pruritus due to AD over the past 24 hours on an NRS scale ranged from 0 (no itching) to 10 (worst itch imaginable), where higher scores indicated greater severity.

Group	Value	95% CI
PF-04965842 100 mg	58.0	11.0 – NA
PF-04965842 200 mg	29.0	8.0 – 87.0
Placebo	112.0	58.0 – NA

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement (EASI-75) From Baseline at Weeks 2, 4 and 8 Secondary · Baseline, Weeks 2, 4, and 8

EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 t

Week 2

Group	Value	95% CI
PF-04965842 100 mg	10.2	5.5 – 14.9
PF-04965842 200 mg	24.3	17.5 – 31.2
Placebo	1.3	0.0 – 3.9

Week 4

Group	Value	95% CI
PF-04965842 100 mg	26.5	19.5 – 33.4
PF-04965842 200 mg	51.0	43.1 – 58.9
Placebo	6.5	1.0 – 12.0

Week 8

Group	Value	95% CI
PF-04965842 100 mg	43.3	35.6 – 51.1
PF-04965842 200 mg	60.4	52.7 – 68.1
Placebo	12.8	5.4 – 20.2

Percentage of Participants Achieving IGA Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Weeks 2, 4 and 8 Secondary · Baseline, Weeks 2, 4, and 8

IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriati

Week 2

Group	Value	95% CI
PF-04965842 100 mg	5.1	1.7 – 8.5
PF-04965842 200 mg	14.5	8.9 – 20.1
Placebo	0	0.0 – 4.7

Week 4

Group	Value	95% CI
PF-04965842 100 mg	14.2	8.7 – 19.7
PF-04965842 200 mg	33.3	25.9 – 40.8
Placebo	1.3	0.0 – 3.8

Week 8

Group	Value	95% CI
PF-04965842 100 mg	22.3	15.8 – 28.8
PF-04965842 200 mg	37.7	30.0 – 45.3
Placebo	10.3	3.5 – 17.0

Percentage of Participants Achieving Investigator's Global Assessment (IGA) Response of Clear (0) at Week 2, 4, 8 and 12 Secondary · Weeks 2, 4, 8 and 12

IGA assesses severity of AD on a 5 point scale (0 to 4, higher scores indicate more severity). Scores: 0= clear, no inflammatory signs of AD; 1= almost clear, AD not fully cleared- light pink residual lesions (except post-inflammatory hyperpigmentation), just perceptible erythema, papulation/induration lichenification, excoriation, and no oozing/crusting; 2= mild AD with light red lesions, slight but definite erythema, papulation/induration, lichenification, excoriation and no oozing/crusting; 3= moderate AD with red lesions, moderate erythema, papulation/induration, lichenification, excoriati

Week 2

Group	Value	95% CI
PF-04965842 100 mg	0	0.0 – 2.3
PF-04965842 200 mg	2.0	0.0 – 4.2
Placebo	0	0.0 – 4.7

Week 4

Group	Value	95% CI
PF-04965842 100 mg	1.9	0.0 – 4.1
PF-04965842 200 mg	4.6	1.3 – 7.9
Placebo	0	0.0 – 4.7

Week 8

Group	Value	95% CI
PF-04965842 100 mg	1.3	0.0 – 3.0
PF-04965842 200 mg	4.5	1.3 – 7.8
Placebo	0	0.0 – 4.6

Week 12

Group	Value	95% CI
PF-04965842 100 mg	5.2	1.7 – 8.6
PF-04965842 200 mg	6.5	2.6 – 10.3
Placebo	0	0.0 – 4.7

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement (EASI-50) From Baseline at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8, and 12

EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 t

Week 2

Group	Value	95% CI
PF-04965842 100 mg	35.7	28.2 – 43.2
PF-04965842 200 mg	55.3	47.4 – 63.2
Placebo	10.5	3.6 – 17.4

Week 4

Group	Value	95% CI
PF-04965842 100 mg	58.7	51.0 – 66.5
PF-04965842 200 mg	78.4	71.9 – 84.9
Placebo	28.6	18.5 – 38.7

Week 8

Group	Value	95% CI
PF-04965842 100 mg	66.2	58.8 – 73.6
PF-04965842 200 mg	82.5	76.5 – 88.5
Placebo	34.6	24.1 – 45.2

Week 12

Group	Value	95% CI
PF-04965842 100 mg	68.4	61.1 – 75.7
PF-04965842 200 mg	79.9	73.5 – 86.2
Placebo	19.5	10.6 – 28.3

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement (EASI-90) From Baseline at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8, and 12

EASI evaluates severity of participants' AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin)\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 t

Week 2

Group	Value	95% CI
PF-04965842 100 mg	2.5	0.1 – 5.0
PF-04965842 200 mg	9.2	4.6 – 13.8
Placebo	0	0.0 – 4.7

Week 4

Group	Value	95% CI
PF-04965842 100 mg	9.7	5.0 – 14.3
PF-04965842 200 mg	22.9	16.2 – 29.5
Placebo	0	0.0 – 4.7

Week 8

Group	Value	95% CI
PF-04965842 100 mg	17.2	11.3 – 23.1
PF-04965842 200 mg	34.4	26.9 – 41.9
Placebo	2.6	0.0 – 6.1

Week 12

Group	Value	95% CI
PF-04965842 100 mg	23.9	17.2 – 30.6
PF-04965842 200 mg	37.7	30.0 – 45.3
Placebo	3.9	0.0 – 8.2

Percentage of Participants Achieving Eczema Area and Severity Index Response of 100% Improvement (EASI-100) From Baseline at Weeks 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8, and 12

EASI evaluates severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to

Week 2

Group	Value	95% CI
PF-04965842 100 mg	0	0.0 – 2.3
PF-04965842 200 mg	1.3	0.0 – 3.1
Placebo	0	0.0 – 4.7

Week 4

Group	Value	95% CI
PF-04965842 100 mg	1.3	0.0 – 3.1
PF-04965842 200 mg	3.9	0.8 – 7.0
Placebo	0	0.0 – 4.7

Week 8

Group	Value	95% CI
PF-04965842 100 mg	1.3	0.0 – 3.0
PF-04965842 200 mg	3.9	0.8 – 7.0
Placebo	0	0.0 – 4.6

Week 12

Group	Value	95% CI
PF-04965842 100 mg	5.2	1.7 – 8.6
PF-04965842 200 mg	7.1	3.1 – 11.2
Placebo	0	0.0 – 4.7

Percent Change From Baseline in Eczema Area and Severity Index (EASI) Total Score at Week 2, 4, 8 and 12 Secondary · Baseline, Weeks 2, 4, 8, and 12

EASI evaluates severity of participant's AD (excluded scalp, palms, soles) based on severity of AD clinical signs and % of body surface area (BSA) affected. Severity of clinical signs of AD (erythema, induration/papulation, excoriation and lichenification) scored separately for each of 4 body regions (head and neck, upper limbs, trunk \[including axillae and groin\] and lower limbs \[including buttocks\]) on 4-point scale: 0= absent; 1= mild; 2= moderate; 3= severe. EASI area score was based upon % BSA with AD in body region: 0 (0%), 1 (\>0 to \<10%), 2 (10 to \<30%), 3 (30 to \<50%), 4 (50 to

Change at Week 2

Group	Value	95% CI
PF-04965842 100 mg	-39.2	-43.8 – -34.7
PF-04965842 200 mg	-51.3	-55.9 – -46.7
Placebo	-9.0	-15.4 – -2.5

Change at Week 4

Group	Value	95% CI
PF-04965842 100 mg	-54.3	-59.1 – -49.5
PF-04965842 200 mg	-69.0	-73.7 – -64.2
Placebo	-24.4	-31.1 – -17.7

Change at Week 8

Group	Value	95% CI
PF-04965842 100 mg	-59.5	-65.0 – -54.0
PF-04965842 200 mg	-73.2	-78.7 – -67.7
Placebo	-33.0	-41.1 – -25.0

Change at Week 12

Group	Value	95% CI
PF-04965842 100 mg	-60.0	-66.5 – -53.6
PF-04965842 200 mg	-73.3	-79.7 – -66.9
Placebo	-28.6	-38.4 – -18.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 16. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PF-04965842 100 mg

Serious: 5/158 (3%)

Deaths: 1/158

PF-04965842 200 mg

Serious: 2/155 (1%)

Deaths: 0/155

Placebo

Serious: 1/78 (1%)

Deaths: 0/78

Serious adverse events (10 terms)

Reaction	System	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Sudden death	General disorders	—	—	—
Anaphylactic shock	Immune system disorders	—	—	—
Eczema herpeticum	Infections and infestations	—	—	—
Herpangina	Infections and infestations	—	—	—
Osteomyelitis bacterial	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Staphylococcal infection	Infections and infestations	—	—	—
Staphylococcal skin infection	Infections and infestations	—	—	—
Femoral neck fracture	Injury, poisoning and procedural complications	—	—	—
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—

Other adverse events (7 terms — click to expand)

Reaction	System	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Nausea	Gastrointestinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Upper respiratory tract infection	Infections and infestations	—	—	—
Headache	Nervous system disorders	—	—	—
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—
Acne	Skin and subcutaneous tissue disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: Sudden death, Anaphylactic shock, Eczema herpeticum, Herpangina, Osteomyelitis bacterial, Pneumonia, Staphylococcal infection, Staphylococcal skin infection.

Data from ClinicalTrials.gov NCT03575871 adverse events section.

Sponsor's own description

B7451013 is a Phase 3 study to evaluate PF-04965842 in patients aged 12 years and older with a minimum body weight of 40 kg who have moderate to severe atopic dermatitis. The efficacy and safety of two dosage strengths of PF-04965842, 100 mg and 200 mg taken orally once daily, will be evaluated relative to placebo over 12 weeks of study participation. Eligible patients will have an option to enter a long-term extension study after completing 12 weeks of treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.
   Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, et al · · 2020 · cited 281× · PMID 32492087 · DOI 10.1001/jamadermatol.2020.1406
2. JAK inhibitors in the treatment of atopic dermatitis.
   Chovatiya R, Paller AS. · · 2021 · cited 258× · PMID 34437922 · DOI 10.1016/j.jaci.2021.08.009
3. Emerging Topical and Systemic JAK Inhibitors in Dermatology.
   Solimani F, Meier K, Ghoreschi K. · · 2019 · cited 199× · PMID 31849996 · DOI 10.3389/fimmu.2019.02847
4. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: An updated review.
   Huang IH, Chung WH, Wu PC, Chen CB. · · 2022 · cited 195× · PMID 36569854 · DOI 10.3389/fimmu.2022.1068260
5. Targeting the Janus Kinase Family in Autoimmune Skin Diseases.
   Howell MD, Kuo FI, Smith PA. · · 2019 · cited 180× · PMID 31649667 · DOI 10.3389/fimmu.2019.02342
6. Selective JAKinibs: Prospects in Inflammatory and Autoimmune Diseases.
   T Virtanen A, Haikarainen T, Raivola J, Silvennoinen O. · · 2019 · cited 164× · PMID 30701418 · DOI 10.1007/s40259-019-00333-w
7. The translational revolution in atopic dermatitis: the paradigm shift from pathogenesis to treatment.
   Facheris P, Jeffery J, Del Duca E, Guttman-Yassky E. · · 2023 · cited 150× · PMID 36928371 · DOI 10.1038/s41423-023-00992-4
8. Efficacy and Safety of Abrocitinib in Combination With Topical Therapy in Adolescents With Moderate-to-Severe Atopic Dermatitis: The JADE TEEN Randomized Clinical Trial.
   Eichenfield LF, Flohr C, Sidbury R, Siegfried E, et al · · 2021 · cited 112× · PMID 34406366 · DOI 10.1001/jamadermatol.2021.2830