NCT03349060: JADE Mono-1

Study to Evaluate 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 10 December 2019

What this trial tests

Phase 3 trial testing PF-04965842 100 mg in Dermatitis, Atopic in 387 participants. Completed in 26 March 2019.

Timeline

7 December 2017

Primary endpoint
26 March 2019

26 March 2019

Quick facts

Lead sponsor	Pfizer
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	387
Start date	7 December 2017
Primary completion	26 March 2019
Estimated completion	26 March 2019
Sites	88 locations across United Kingdom, Germany, Hungary, Poland, Canada, Australia, United States, Czechia

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	23.7
PF-04965842 200 mg	43.8
Placebo	7.9

Percentage of Participants Achieving Eczema Area and Severity Index (EASI) Response of >=75 Percent (%) Improvement 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 t

Group	Value	95% CI
PF-04965842 100 mg	39.7
PF-04965842 200 mg	62.7
Placebo	11.8

Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale (NRS) for Severity of Pruritus at Week 2, 4, 8 and 12: Full Analysis Set (FAS) Secondary · Baseline, Week 2, 4, 8, 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	20.4
PF-04965842 200 mg	45.6
Placebo	2.7

Week 4

Group	Value	95% CI
PF-04965842 100 mg	32.2
PF-04965842 200 mg	58.8
Placebo	17.2

Week 8

Group	Value	95% CI
PF-04965842 100 mg	34.3
PF-04965842 200 mg	59.9
Placebo	14.4

Week 12

Group	Value	95% CI
PF-04965842 100 mg	37.7
PF-04965842 200 mg	57.2
Placebo	15.3

Percentage of Participants With at Least 4 Points Improvement From Baseline in the Numerical Rating Scale for Severity of Pruritus at Week 2, 4 and 12: Per Protocol Analysis Set (PPAS) Secondary · Baseline, Week 2, 4, 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	20.5
PF-04965842 200 mg	47.6
Placebo	3.7

Week 4

Group	Value	95% CI
PF-04965842 100 mg	34.0
PF-04965842 200 mg	63.3
Placebo	20.7

Week 12

Group	Value	95% CI
PF-04965842 100 mg	41.1
PF-04965842 200 mg	60.6
Placebo	12.3

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis (PSAAD) Total Score at Week 2, 4, 8 and 12: Full Analysis Set Secondary · Baseline, Week 2, 4, 8, 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

Change at Week 2

Group	Value	95% CI
PF-04965842 100 mg	-1.5	-1.7 – -1.2
PF-04965842 200 mg	-2.1	-2.3 – -1.8
Placebo	-0.5	-0.8 – -0.1

Change at Week 4

Group	Value	95% CI
PF-04965842 100 mg	-1.8	-2.1 – -1.5
PF-04965842 200 mg	-3.0	-3.2 – -2.7
Placebo	-0.7	-1.1 – -0.3

Change at Week 8

Group	Value	95% CI
PF-04965842 100 mg	-2.2	-2.5 – -1.8
PF-04965842 200 mg	-3.1	-3.5 – -2.8
Placebo	-1.2	-1.7 – -0.7

Change at Week 12

Group	Value	95% CI
PF-04965842 100 mg	-2.2	-2.6 – -1.9
PF-04965842 200 mg	-3.2	-3.6 – -2.8
Placebo	-1.1	-1.7 – -0.6

Change From Baseline in Pruritus and Symptoms Assessment for Atopic Dermatitis Total Score at Week 12: Per Protocol Analysis Set 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	-3.4	-3.8 – -3.0
Placebo	-1.1	-1.7 – -0.5

Time to Achieve >=4 Points Improvement From Baseline in Numerical Rating Scale for Severity of Pruritus Secondary · Baseline up to Week 12

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. 95% CI was based on the Brookmeyer and Crowley method.

Group	Value	95% CI
PF-04965842 100 mg	84.0	56.0 – NA
PF-04965842 200 mg	14.0	11.0 – 29.0
Placebo	92.0	85.0 – NA

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=75% Improvement From Baseline at Week 2, 4 and 8 Secondary · Baseline, Week 2, 4, 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	10.3
PF-04965842 200 mg	24.0
Placebo	3.9

Week 4

Group	Value	95% CI
PF-04965842 100 mg	27.6
PF-04965842 200 mg	47.4
Placebo	14.5

Week 8

Group	Value	95% CI
PF-04965842 100 mg	38.3
PF-04965842 200 mg	57.8
Placebo	13.3

Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) or Almost Clear (1) and >=2 Points Improvement From Baseline at Week 2, 4 and 8 Secondary · Baseline, Week 2, 4, 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	3.9
PF-04965842 200 mg	9.7
Placebo	0

Week 4

Group	Value	95% CI
PF-04965842 100 mg	10.5
PF-04965842 200 mg	27.0
Placebo	5.3

Week 8

Group	Value	95% CI
PF-04965842 100 mg	20.3
PF-04965842 200 mg	35.7
Placebo	6.7

Percentage of Participants Achieving Investigator's Global Assessment Response of Clear (0) at Week 2, 4, 8 and 12 Secondary · Week 2, 4, 8, 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
PF-04965842 200 mg	0
Placebo	0

Week 4

Group	Value	95% CI
PF-04965842 100 mg	0
PF-04965842 200 mg	6.6
Placebo	0

Week 8

Group	Value	95% CI
PF-04965842 100 mg	4.6
PF-04965842 200 mg	11.7
Placebo	0

Week 12

Group	Value	95% CI
PF-04965842 100 mg	7.1
PF-04965842 200 mg	13.1
Placebo	0

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=50% Improvement From Baseline at Week 2, 4, 8 and 12 Secondary · Baseline, Week 2, 4, 8, 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	34.2
PF-04965842 200 mg	55.2
Placebo	10.4

Week 4

Group	Value	95% CI
PF-04965842 100 mg	54.6
PF-04965842 200 mg	73.7
Placebo	21.1

Week 8

Group	Value	95% CI
PF-04965842 100 mg	57.8
PF-04965842 200 mg	76.6
Placebo	24.0

Week 12

Group	Value	95% CI
PF-04965842 100 mg	57.7
PF-04965842 200 mg	75.8
Placebo	22.4

Percentage of Participants Achieving Eczema Area and Severity Index Response of >=90% Improvement From Baseline at Week 2, 4, 8 and 12 Secondary · Baseline, Week 2, 4, 8, 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	1.9
PF-04965842 200 mg	5.2
Placebo	1.3

Week 4

Group	Value	95% CI
PF-04965842 100 mg	7.9
PF-04965842 200 mg	24.3
Placebo	3.9

Week 8

Group	Value	95% CI
PF-04965842 100 mg	14.3
PF-04965842 200 mg	33.1
Placebo	5.3

Week 12

Group	Value	95% CI
PF-04965842 100 mg	18.6
PF-04965842 200 mg	38.6
Placebo	5.3

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: 5/156 (3%)

Deaths: 0/156

PF-04965842 200 mg

Serious: 5/154 (3%)

Deaths: 0/154

Placebo

Serious: 3/77 (4%)

Deaths: 0/77

Serious adverse events (11 terms)

Reaction	System	PF-04965842 100 mg	PF-04965842 200 mg	Placebo
Asthma	Respiratory, thoracic and mediastinal disorders	—	—	—
Retinal detachment	Eye disorders	—	—	—
Inflammatory bowel disease	Gastrointestinal disorders	—	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—	—
Appendicitis	Infections and infestations	—	—	—
Peritonsillitis	Infections and infestations	—	—	—
Dehydration	Metabolism and nutrition disorders	—	—	—
Meniscal degeneration	Musculoskeletal and connective tissue disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Seizure	Nervous system disorders	—	—	—
Dermatitis atopic	Skin and subcutaneous tissue disorders	—	—	—

Other adverse events (5 terms — click to expand)

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

Most-reported serious reactions: Asthma, Retinal detachment, Inflammatory bowel disease, Pancreatitis acute, Appendicitis, Peritonsillitis, Dehydration, Meniscal degeneration.

Data from ClinicalTrials.gov NCT03349060 adverse events section.

Sponsor's own description

B7451012 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 adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.
   Simpson EL, Sinclair R, Forman S, Wollenberg A, et al · · 2020 · cited 337× · PMID 32711801 · DOI 10.1016/s0140-6736(20)30732-7
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. JAK-inhibitors. New players in the field of immune-mediated diseases, beyond rheumatoid arthritis.
   Fragoulis GE, McInnes IB, Siebert S. · · 2019 · cited 223× · PMID 30806709 · DOI 10.1093/rheumatology/key276
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