Trial Outcomes & Findings for A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Atopic Dermatitis (NCT NCT02424253)

Last Updated: 2021-06-10

Results Overview

The participant used the Pruritus NRS to rate his or her worst itch in the previous 12 hours. This was assessed twice daily (in the morning soon after rising and the evening prior to retiring) and recorded in the eDiary. The scale ranges from 0 (no itching) to 10 (itching as bad as can be imagined). If only 1 measurement was collected on a particular day, that score was counted as the worst measurement.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

98 participants

Primary outcome timeframe

Baseline to Week 8

Results posted on

2021-06-10

Participant Flow

The first informed consent was on 18 May 2015. Subjects were randomly assigned 2:1 to receive either 30 mg ZPL-3893787 or matching placebo. The randomization was stratified by baseline worst daily pruritus NRS score (≤ 7.5 and \> 7.5) determined from the mean pruritus score (worst itch over 24 hours) collected during the 7-day Run-in Period.

Participant milestones

Participant milestones
Measure	ZPL-3893787 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo 1 capsule orally once daily for 8 weeks.
Overall Study STARTED	65	33
Overall Study COMPLETED	54	24
Overall Study NOT COMPLETED	11	9

Reasons for withdrawal

Reasons for withdrawal
Measure	ZPL-3893787 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo 1 capsule orally once daily for 8 weeks.
Overall Study Other, unspecified	1	0
Overall Study Compliance problems	1	0
Overall Study Physician Decision	2	0
Overall Study Lack of Efficacy	0	7
Overall Study Adverse Event	2	0
Overall Study Consent withdrawn by subject	4	1
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Atopic Dermatitis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ZPL-3893787 n=65 Participants 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo n=33 Participants 1 capsule orally once daily for 8 weeks.	Total n=98 Participants Total of all reporting groups
Age, Continuous	33.7 years STANDARD_DEVIATION 11.22 • n=93 Participants	35.5 years STANDARD_DEVIATION 12.52 • n=4 Participants	34.3 years STANDARD_DEVIATION 11.64 • n=27 Participants
Sex: Female, Male Female	36 Participants n=93 Participants	20 Participants n=4 Participants	56 Participants n=27 Participants
Sex: Female, Male Male	29 Participants n=93 Participants	13 Participants n=4 Participants	42 Participants n=27 Participants
Fitzpatrick Skin Type Type I	2 participants n=93 Participants	4 participants n=4 Participants	6 participants n=27 Participants
Fitzpatrick Skin Type Type II	24 participants n=93 Participants	11 participants n=4 Participants	35 participants n=27 Participants
Fitzpatrick Skin Type Type III	32 participants n=93 Participants	14 participants n=4 Participants	46 participants n=27 Participants
Fitzpatrick Skin Type Type IV	3 participants n=93 Participants	2 participants n=4 Participants	5 participants n=27 Participants
Fitzpatrick Skin Type Type V	3 participants n=93 Participants	1 participants n=4 Participants	4 participants n=27 Participants
Fitzpatrick Skin Type Type VI	1 participants n=93 Participants	1 participants n=4 Participants	2 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline to Week 8

Population: Full Analysis Set (FAS): Included all randomized subjects who received at least 1 dose of study drug.

Outcome measures

Outcome measures
Measure	ZPL-3893787 n=65 Participants 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo n=33 Participants 1 capsule orally once daily for 8 weeks.
Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) Baseline summary	7.3 score on a scale Standard Deviation 1.139	7.26 score on a scale Standard Deviation 1.054
Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) Week 8 summary	4.27 score on a scale Standard Deviation 2.253	4.6 score on a scale Standard Deviation 1.95
Change From Baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch) Change from Baseline	-3.03 score on a scale Standard Deviation 2.186	-2.66 score on a scale Standard Deviation 2.057

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: FAS: All randomized subjects who received at least one dose of study treatment.

The EASI is a validated tool used to measure the severity and extent of atopic eczema over 4 body regions (head and neck, upper limbs, trunk, and lower limbs). The intensity of a representative area of eczema and the approximate percentage affected by eczema are calculated for each region. A representative area of eczema is selected for each body region. The intensity of redness (erythema), thickness (induration, papulation, and edema), scratching (excoriation), and lichenification (lined skin) of eczema is assessed as: 0 - None 1. \- Mild 2. \- Moderate 3. \- Severe The total score incorporates the extent of body regions affected. Scores range from 0 to 72 with higher scores indicating more severe eczema. Total score is calculated by summing the EASI scores of 6 symptoms across 4 body regions

Outcome measures

Outcome measures
Measure	ZPL-3893787 n=65 Participants 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo n=33 Participants 1 capsule orally once daily for 8 weeks.
Change From Baseline in Eczema Area and Severity Index (EASI) Score Baseline	21.39 score on a scale Standard Deviation 7.889	20.44 score on a scale Standard Deviation 6.868
Change From Baseline in Eczema Area and Severity Index (EASI) Score Week 8 summary	10.67 score on a scale Standard Deviation 9.541	15.06 score on a scale Standard Deviation 11.159
Change From Baseline in Eczema Area and Severity Index (EASI) Score Week 8 change from baseline	-10.72 score on a scale Standard Deviation 9.679	-5.38 score on a scale Standard Deviation 9.922

Adverse Events

ZPL-3893787

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ZPL-3893787 n=65 participants at risk 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo n=33 participants at risk 1 capsule orally once daily for 8 weeks.
Eye disorders Ulcerative keratitis (ulcus corneae left eye)	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of the agreements with investigators may vary. However, the investigator is not prohibited from publishing. Any publications from a single site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	ZPL-3893787 n=65 participants at risk 30 mg ZPL-3893787 orally once daily for 8 weeks.	Placebo n=33 participants at risk 1 capsule orally once daily for 8 weeks.
Cardiac disorders Bradycardia	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Cardiac disorders Sinus arrhythmia	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Cardiac disorders Sinus bradycardia	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Nervous system disorders Headache	9.2% 6/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	12.1% 4/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Nervous system disorders Somnolence	3.1% 2/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Nervous system disorders Dizziness	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
General disorders Pain	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
General disorders Thirst	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
General disorders Drug ineffective	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
General disorders Fatigue	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
General disorders Decreased activity	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Gastrointestinal disorders Nausea	3.1% 2/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Gastrointestinal disorders Abdominal pain	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Reproductive system and breast disorders Menorrhagia	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Skin and subcutaneous tissue disorders Erythema	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Skin and subcutaneous tissue disorders Urticaria	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	6.1% 2/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Skin and subcutaneous tissue disorders Pruritus	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Musculoskeletal and connective tissue disorders Arthralgia	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Musculoskeletal and connective tissue disorders Muscle spasms	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Infections and infestations Nasopharyngitis	1.5% 1/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	0.00% 0/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Infections and infestations Folliculitis	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.
Infections and infestations Urinary tract infection	0.00% 0/65 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.	3.0% 1/33 • Adverse events were collected from Screening to up to 28 days post last dose, up to approximately 10 months.