Trial Outcomes & Findings for A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Plaque Psoriasis (NCT NCT02618616)

NCT ID: NCT02618616

Last Updated: 2021-07-20

Results Overview

The PASI is an assessment routinely used for evaluating and grading the severity of psoriatic lesions and their response to therapy. PASI divides the body into 4 regions: the head, trunk, upper extremities (arms) and lower extremities (legs). Each of these areas is assessed separately for erythema, in duration and scaling; these symptoms are scored on a 5-point scale from 0-4, where 0 = no symptoms and 4 =very marked. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents a reduction of at least 75% from baseline in the PASI score.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 129 participants
• Primary outcome timeframe: From baseline to week 12
• Results posted on: 2021-07-20

Participant Flow

Each subject had a screening visit to confirm suitability to enter the study, followed by 7-day run-in period.

Participant milestones

Measure	ZPL-389 Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally once daily (OD) for 12 weeks.	Placebo Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Overall Study STARTED	87	42
Overall Study COMPLETED	66	35
Overall Study NOT COMPLETED	21	7

Reasons for withdrawal

Measure	ZPL-389 Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally once daily (OD) for 12 weeks.	Placebo Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Overall Study Lack of Efficacy	4	0
Overall Study Pregnancy	0	1
Overall Study Adverse Event	8	0
Overall Study Failure to comply with dosing/evaluation	1	0
Overall Study Consent withdrawn by subject	8	5
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

A Study to Determine the Efficacy of ZPL-3893787 in Subjects With Plaque Psoriasis

Baseline characteristics by cohort

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.	Total n=129 Participants Total of all reporting groups
Age, Continuous	44.5 years STANDARD_DEVIATION 13.82 • n=5 Participants	43.2 years STANDARD_DEVIATION 12.64 • n=7 Participants	44.1 years STANDARD_DEVIATION 13.41 • n=5 Participants
Sex/Gender, Customized Female	33 Participants n=5 Participants	15 Participants n=7 Participants	48 Participants n=5 Participants
Sex/Gender, Customized Male	54 Participants n=5 Participants	27 Participants n=7 Participants	81 Participants n=5 Participants
Body Mass Index (BMI)	28.24 kg/m^2 STANDARD_DEVIATION 3.494 • n=5 Participants	27.86 kg/m^2 STANDARD_DEVIATION 3.575 • n=7 Participants	28.12 kg/m^2 STANDARD_DEVIATION 3.509 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline to week 12

Population: Full analysis set (FAS): All randomized subjects who received at least one dose of study treatment.

The PASI is an assessment routinely used for evaluating and grading the severity of psoriatic lesions and their response to therapy. PASI divides the body into 4 regions: the head, trunk, upper extremities (arms) and lower extremities (legs). Each of these areas is assessed separately for erythema, in duration and scaling; these symptoms are scored on a 5-point scale from 0-4, where 0 = no symptoms and 4 =very marked. The PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. A PASI 75 response represents a reduction of at least 75% from baseline in the PASI score.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Percent Change From Baseline in Psoriasis Assessment of Severity Index (PASI) at Week 12	-28.043 percentage change Standard Deviation 38.4436	-37.361 percentage change Standard Deviation 32.3581

SECONDARY outcome

Timeframe: From baseline to week 12

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

PASI-75 and PASI-50 are defined as a 75% and 50% reduction, respectively, from baseline in PASI score at Week 12.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
PASI-50 and PASI-75 Responders at Week 12 PASI-50	21 Participants	15 Participants
PASI-50 and PASI-75 Responders at Week 12 PASI-75	12 Participants	6 Participants

SECONDARY outcome

Timeframe: From baseline to week 12

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

An overall assessment of the severity of psoriasis was made, by the investigator, using the IGA at each visit. IGA scores take values on a 5-point scale from 0-4, where 0 = clear to 4 = severe disease. Responder is defined as a score of clear or almost clear, or a reduction of ≥2 levels. Success is defined as a score of clear or almost clear. Subjects with discontinued and missing data categories at Week 12 were considered non-responders.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Improvement in Investigator Global Assessment (IGA) at Week 12 Responder	10 participants	6 participants
Improvement in Investigator Global Assessment (IGA) at Week 12 Success	7 participants	3 participants

SECONDARY outcome

Timeframe: From baseline to week 12

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

The pruritus NRS is an assessment tool used to assess the subject's worst itch as a result of psoriasis in the last 12 hours. The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. They were asked the following question: On a scale of 0 (no itching) to 10 (itching as bad as you can imagine), please rate the worst itching that you felt over the last 12 hours.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Change From Baseline in the Numerical Rating Scale (NRS) for Pruritus (Worst Itch) at Week 12	-1.40 percent change Standard Deviation 2.659	-1.78 percent change Standard Deviation 2.810

SECONDARY outcome

Timeframe: From baseline to week 12

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

At the end of treatment (Week 12) or early termination visit, the subject was asked to rate their degree of improvement (or worsening) of their psoriasis compared to before the start of treatment with study drug, using a 7-point scale, standardized PGIC.

Since the start of the study (dosing), my overall status is:

1. Very much improved

2. Much improved

3. Minimally improved

4. No change

5. Minimally worse

6. Much worse

7. Very much worse

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Patient Global Impression of Change (PGIC) a Week 12 Much improved	14 participants	9 participants
Patient Global Impression of Change (PGIC) a Week 12 Very much worse	8 participants	1 participants
Patient Global Impression of Change (PGIC) a Week 12 Missing	4 participants	2 participants
Patient Global Impression of Change (PGIC) a Week 12 Very much improved	12 participants	3 participants
Patient Global Impression of Change (PGIC) a Week 12 Minimally improved	22 participants	11 participants
Patient Global Impression of Change (PGIC) a Week 12 No change	15 participants	7 participants
Patient Global Impression of Change (PGIC) a Week 12 Minimally worse	5 participants	3 participants
Patient Global Impression of Change (PGIC) a Week 12 Much worse	7 participants	6 participants

SECONDARY outcome

Timeframe: From baseline to week 12

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

Assessment of the percentage of a subject's BSA affected by psoriasis was made by best estimates of the investigator at each visit. Hand-size measurement was considered to be the "best estimate" to measure the BSA by the investigators.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Change From Baseline in Body Surface Area (BSA) and Percentage Change From Baseline at Week 12	-2.8 percentage of BSA Standard Deviation 10.77	-4.2 percentage of BSA Standard Deviation 9.62

SECONDARY outcome

Timeframe: From baseline to week 12

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

The subjects completed the NRS each morning on (or soon after) rising and evening prior to retiring to bed. They were asked the following question: On a scale of 0 (no itching) to 10 (itching as bad as you can imagine), please rate the worst itching that you felt over the last 12 hours.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Change From Baseline in the Daytime and Night Time NRS for Pruritus (Worst Itch) at Week 12 NRS for pruritus (daytime) at baseline	4.32 score on a scale Standard Deviation 2.251	4.52 score on a scale Standard Deviation 2.748
Change From Baseline in the Daytime and Night Time NRS for Pruritus (Worst Itch) at Week 12 Change in baseline at Week 12 (daytime)	-1.40 score on a scale Standard Deviation 2.765	-1.42 score on a scale Standard Deviation 2.779
Change From Baseline in the Daytime and Night Time NRS for Pruritus (Worst Itch) at Week 12 NRS for pruritus (night time) at baseline	4.19 score on a scale Standard Deviation 2.299	4.34 score on a scale Standard Deviation 2.682
Change From Baseline in the Daytime and Night Time NRS for Pruritus (Worst Itch) at Week 12 Change in baseline at Week 12 (night time)	-1.35 score on a scale Standard Deviation 2.856	-1.31 score on a scale Standard Deviation 2.860

SECONDARY outcome

Timeframe: From baseline to week 12

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

In the morning subjects were asked the following question to determine the level of sleep disturbance due to itching: On a scale of 0 (no sleep disturbance) to 10 (awake all night), please rate how much your sleep was disturbed by itch last night.

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Change From Baseline in the NRS for Sleep Disturbance at Week 12 NRS for pruritus (sleep disturbance) at baseline	2.48 score on a scale Standard Deviation 2.172	2.74 score on a scale Standard Deviation 2.559
Change From Baseline in the NRS for Sleep Disturbance at Week 12 Change in baseline at Week 12 (sleep disturbance)	-0.88 score on a scale Standard Deviation 2.417	-0.93 score on a scale Standard Deviation 2.098

SECONDARY outcome

Timeframe: From baseline to week 12

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

Subjects were asked the following question to determine their duration of itching: Over the last 12 hours approximately how many hours, if any, did you itch?

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 Total duration of itching- Baseline	5.74 hours Standard Deviation 4.608	6.68 hours Standard Deviation 5.637
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 Total duration of itching- Change at week 12	-1.15 hours Standard Deviation 4.525	-1.16 hours Standard Deviation 5.543
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 Daytime duration of itching-Baseline	3.16 hours Standard Deviation 2.682	3.57 hours Standard Deviation 2.994
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 Daytime duration of itching-Change at week 12	-0.60 hours Standard Deviation 2.399	3.63 hours Standard Deviation 3.034
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 Night time duration of itching-Baseline	2.58 hours Standard Deviation 2.072	3.11 hours Standard Deviation 2.720
Change From Baseline in Total, Daytime and Night Time Duration of Itching at Week 12 Night time duration of itching-Change at week 12	-0.55 hours Standard Deviation 2.188	-0.43 hours Standard Deviation 2.581

SECONDARY outcome

Timeframe: From baseline to week 12

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

Subjects were asked to rate their itch over the last 12 hours using a list of adjectives describing different levels of symptom intensity: Over the last 12 hours how would you rate your itch? No itch; Mild; Moderate and Severe; Pruritus was evaluated by the subject, using the eDiary, twice daily for 1 week prior to the start of study treatment (run-in period) and during treatment (baseline to Day 84).

Outcome measures

Measure	ZPL-389 n=87 Participants Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 Participants Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Discontinued	21 Participants	7 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Baseline - No itch	2 Participants	2 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Baseline - Mild	21 Participants	17 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Baseline - Moderate	52 Participants	14 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Baseline - Severe	12 Participants	9 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Week 12 - No itch	17 Participants	11 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Week 12 - Mild	19 Participants	10 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Week 12 - Moderate	24 Participants	12 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Week 12 - Severe	3 Participants	0 Participants
Number of Participants for Each Verbal Rating Scale (VRS) Score for Pruritus at Week 12 Missing	3 Participants	2 Participants

Adverse Events

ZPL-389

Serious events: 5 serious events

Other events: 26 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	ZPL-389 n=87 participants at risk Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 participants at risk Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Gastrointestinal disorders Pancreatitis	1.1% 1/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Gastrointestinal disorders Pancreatitis acute	1.1% 1/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Hepatobiliary disorders Hepatitis	1.1% 1/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Skin and subcutaneous tissue disorders Erythrodermic psoriasis	1.1% 1/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Skin and subcutaneous tissue disorders Psoriasis	1.1% 1/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Infections and infestations Cellulitis	1.1% 1/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment

Other adverse events

Measure	ZPL-389 n=87 participants at risk Each subject was given 30 mg ZPL-3893787 capsules, to be taken orally OD for 12 weeks.	Placebo n=42 participants at risk Each subject was given 30 mg capsules of matching placebo, to be taken orally OD for 12 weeks.
Nervous system disorders Headache	5.7% 5/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	7.1% 3/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Skin and subcutaneous tissue disorders Pruritus	5.7% 5/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	0.00% 0/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Skin and subcutaneous tissue disorders Psoriasis	12.6% 11/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	2.4% 1/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment
Infections and infestations Nasopharyngitis	5.7% 5/87 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment	4.8% 2/42 • Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment up to maximum duration of 16 weeks Adverse events (AEs) are any untoward sign or symptom that occured during the study treatment

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

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