ARROW: Comparison of Secukinumab Versus Guselkumab in Clearing Psoriatic Plaques Refractory to Ustekinumab

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03553823
• Collaborator: (none)
• Enrollment: 40
• Locations: 14
• Arms: 2
• Actual Duration (Months): 12.5
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The aim of this study was to describe the effect of direct IL-17A inhibition with secukinumab as compared with the selective inhibition of IL-23 with guselkumab (p19 subunit blocker) in controlling inflammation in psoriatic plaques that remain active despite treatment with the non-selective IL-23 inhibitor ustekinumab (blocker of p40 subunit, shared by IL-12 and IL 23).

Condition or Disease	Intervention/Treatment	Phase
Chronic Plaque-type Psoriasis	Procedure: Skin biopsies	Phase 2

Detailed Description

This was a 16-week, randomized, open-label, parallel-group, active-control, Phase 2a study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab. Forty subjects will be randomized 1:1 and treated for 16 weeks. In each patient, a target active refractory skin plaque (TCS ≥6) is described and biopsied at baseline and at study end. The objective of the study was to assess the superiority of secukinumab over guselkumab in achieving clear/almost clear status (TCS 0-2) of the target plaques; and to describe the molecular mechanisms behind this difference

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This was a 16-week, randomized, open-label, parallel-group, active-control study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab.This was a 16-week, randomized, open-label, parallel-group, active-control study comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque psoriasis who had an inadequate response to ustekinumab.
• Masking: Single (Outcomes Assessor)
• Masking Description: Blinded outcome assessor assessed subjects on each visit for target plaque TCS, PASI, IGA, BSA, ppIGA, PSSI, NAPS.
• Primary Purpose: Treatment
• Official Title: A 16-week Randomized, Open-label, Multicenter Study to Assess the Superiority of Secukinumab Over Guselkumab in the Complete Treatment of Ustekinumab Resistant Psoriatic Plaques
• Actual Study Start Date: Jan 14, 2019
• Actual Primary Completion Date: Jan 28, 2020
• Actual Study Completion Date: Jan 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: secukinumab 20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered 300 mg secukinumab as two 150-mg s.c. injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive	Procedure: Skin biopsies; At Baseline, two 6-mm punch biopsies were taken, one from the identified active plaque (TCS ≥ 6) and one from never-lesional skin. At the End-of-study Visit, one biopsy was taken from the same area of the active plaque sampled at Baseline.
Active Comparator: Guselkumab 20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12.	Procedure: Skin biopsies; At Baseline, two 6-mm punch biopsies were taken, one from the identified active plaque (TCS ≥ 6) and one from never-lesional skin. At the End-of-study Visit, one biopsy was taken from the same area of the active plaque sampled at Baseline.

Outcome Measures

Primary Outcome Measures

1. Proportion of Subjects Whose Plaque Achieves "Clear" or "Almost Clear" Status (TCS = 0-2) [16 week]

   Total clinical score: number (%) of subjects who responded at Week 16 (FAS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Chronic plaque-type psoriasis considered inadequately controlled after treatment with ustekinumab according to the following criteria-:

• Ustekinumab administered at a dose equal or higher than that on the label for at least 24 weeks. The last administration must be at least 12 weeks before randomization

• absolute PASI score of 1-10 at Screening

• Presence of at least 1 refractory skin plaque, defined by a TCS of at least 6 and severity score of at least 2 or 3 (moderate) for each individual item, with an area ≥ 10 cm2 at screening.

Exclusion Criteria:

• Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at Screening or Baseline

• Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium) at Baseline

• Previous treatment with more than one TNFα inhibitor or with IL-17A (including secukinumab), IL-17R or IL-23 (including guselkumab) inhibitors

• Use of other investigational drugs within 4 weeks before enrolment, or within a period of 5 half lives of enrollment/initiation of the study treatment, whichever is longer

• Ongoing use of prohibited treatments (see Section 6.2.2)

• Known immunosuppression (e.g., AIDS) at Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	New Orleans	Louisiana	United States	70112
2	Novartis Investigative Site	East Windsor	New Jersey	United States	08520
3	Novartis Investigative Site	Philadelphia	Pennsylvania	United States	19140
4	Novartis Investigative Site	Dallas	Texas	United States	75230
5	Novartis Investigative Site	Verdun	Quebec	Canada	H4G 3E7
6	Novartis Investigative Site	Berlin		Germany	13353
7	Novartis Investigative Site	Bochum		Germany	44791
8	Novartis Investigative Site	Bonn		Germany	53105
9	Novartis Investigative Site	Frankfurt		Germany	60590
10	Novartis Investigative Site	Halle (Saale)		Germany	06108
11	Novartis Investigative Site	Hamburg		Germany	22391
12	Novartis Investigative Site	Kiel		Germany	24105
13	Novartis Investigative Site	Memmingen		Germany	87700
14	Novartis Investigative Site	Selters		Germany	56242

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 22, 2018
• Statistical Analysis Plan - Apr 15, 2019

More Information

Additional Information:

• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03553823
• Other Study ID Numbers: CAIN457A2403; 2018-001048-70
• First Posted: Jun 12, 2018
• Last Update Posted: Oct 11, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Novartis Pharmaceuticals: Psoriasis; Plaque psoriasis; Secukinumab; Skin condition; skin disease; itching; psoriasis vulgaris; immune-mediated systemic disease; skin lesions; scaly patches; papules
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Recruitment Details	The Screening Phase was completed by 40 (95.2%) of the 42 subjects screened. One (2.4%) subject was rescreened and 2 (4.8%) subjects failed screening
Pre-assignment Detail	39 (97.5%) subjects completed this trial

Arm/Group Title	Secukinumab	Guselkumab
Arm/Group Description	20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered 300 mg secukinumab as two 150-mg s.c. injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive	20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12.
Period Title: Overall Study
STARTED	20	20
COMPLETED	20	19
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Secukinumab	Guselkumab	Total
Arm/Group Description	20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered 300 mg secukinumab as two 150-mg s.c. injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive	20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12.	Total of all reporting groups
Overall Participants	20	20	40
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	17 85%	19 95%	36 90%
>=65 years	3 15%	1 5%	4 10%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.6 (15.10)	48.5 (12.30)	48.1 (13.60)
Sex: Female, Male (Count of Participants)
Female	6 30%	5 25%	11 27.5%
Male	14 70%	15 75%	29 72.5%
Race/Ethnicity, Customized (Count of Participants)
White	17 85%	20 100%	37 92.5%
Black or African American	2 10%	0 0%	2 5%
Asian	1 5%	0 0%	1 2.5%

Outcome Measures

1. Primary Outcome

Title	Proportion of Subjects Whose Plaque Achieves "Clear" or "Almost Clear" Status (TCS = 0-2)
Description	Total clinical score: number (%) of subjects who responded at Week 16 (FAS)
Time Frame	16 week

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) comprised all subjects to whom study treatment had been assigned by randomization. According to the intent-to-treat principle, subjects were analyzed according to the treatment they were assigned to during the randomization procedure.

Arm/Group Title	Secukinumab	Guselkumab
Arm/Group Description	20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered 300 mg secukinumab as two 150-mg s.c. injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive	20 subjects with plaque psoriasis with an inadequate response to ustekinumab self-administered guselkumab as 100 mg s.c. injections at Baseline, Weeks 4, and 12.
Measure Participants	20	20
Count of Participants [Participants]	12 60%	8 40%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Secukinumab, Guselkumab
	Comments	Proportion of subjects whose plaque achieves "clear" or "almost clear" status (TCS = 0-2)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1715
	Comments
	Method	Fisher Exact
	Comments	The statistical model was the Fisher's exact test for the difference in proportions.
Method of Estimation	Estimation Parameter	Difference secukinumab vs guselkumab
	Estimated Value	20.0
	Confidence Interval	(2-Sided) 95%; -13.3 to 50.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse Events were collected for duration of study to week 16
Adverse Event Reporting Description	Adverse Events (AEs) are any untoward sign or symptom that occurs during the study treatment period
Arm/Group Title	Secukinumab		Guselkumab
Arm/Group Description	Secukinumab		Guselkumab
All Cause Mortality
	Secukinumab		Guselkumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/20 (0%)
Serious Adverse Events
	Secukinumab		Guselkumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/20 (10%)		1/20 (5%)
Gastrointestinal disorders
Gastritis	1/20 (5%)		0/20 (0%)
Hepatobiliary disorders
Cholelithiasis	0/20 (0%)		1/20 (5%)
Infections and infestations
Pneumonia	1/20 (5%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Secukinumab		Guselkumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/20 (55%)		5/20 (25%)
Eye disorders
Dacryostenosis acquired	1/20 (5%)		0/20 (0%)
Infections and infestations
Bronchitis	0/20 (0%)		1/20 (5%)
Erysipelas	1/20 (5%)		0/20 (0%)
Herpes zoster	1/20 (5%)		0/20 (0%)
Nasopharyngitis	2/20 (10%)		1/20 (5%)
Postoperative wound infection	1/20 (5%)		0/20 (0%)
Sepsis	1/20 (5%)		0/20 (0%)
Vulvovaginal mycotic infection	1/20 (5%)		0/20 (0%)
Injury, poisoning and procedural complications
Wound dehiscence	1/20 (5%)		0/20 (0%)
Investigations
Blood bilirubin increased	1/20 (5%)		0/20 (0%)
Metabolism and nutrition disorders
Gout	2/20 (10%)		0/20 (0%)
Hyperglycaemia	1/20 (5%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/20 (0%)		1/20 (5%)
Renal and urinary disorders
Acute kidney injury	1/20 (5%)		0/20 (0%)
Reproductive system and breast disorders
Balanoposthitis	1/20 (5%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/20 (5%)		0/20 (0%)
Skin and subcutaneous tissue disorders
Dyshidrotic eczema	0/20 (0%)		1/20 (5%)
Eczema	0/20 (0%)		1/20 (5%)
Hyperhidrosis	0/20 (0%)		1/20 (5%)
Miliaria	1/20 (5%)		0/20 (0%)

Limitations/Caveats

Analysis of biomarkers is delayed due to the global coronavirus pandemic of 2020, thus, the biomarker-related exploratory objectives were not evaluated in this present report; but will be presented in a voluntary future update.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.