Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed IL-17A Therapies

• Sponsor: Icahn School of Medicine at Mount Sinai (Other)
• Overall Status: Completed
• CT.gov ID: NCT03403036
• Collaborator: (none)
• Enrollment: 39
• Locations: 2
• Arm: 1
• Actual Duration (Months): 9.6
• Patients Per Site: 19.5
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with interleukin (IL)-17A therapies. Forty patients will be enrolled in this 16-week open-label study. Patients will receive 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. The primary efficacy endpoint will be the proportion of patients achieving a score of "0-clear" or "1-almost clear" in the sPGA score after 16 weeks of treatment. After completion of the 16-week trial, patients may desire to continue treatment with brodalumab.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Brodalumab	Phase 4

Detailed Description

This study will evaluate the safety and efficacy of brodalumab in the treatment of moderate-to-severe psoriasis in patients who have previously failed treatment with interleukin (IL)-17A therapies. Failure of IL-17A therapy will be defined as previous treatment with either secukinumab or ixekizumab for at least 3 months without achieving PASI-75 response or a 50% loss of original improvement. Forty patients will be enrolled in this 16-week open-label study. Patients will be enrolled at three to four different sites in the US. After enrollment, study visits will occur at monthly intervals, with patients receiving 210 mg of brodalumab subcutaneous injection at weeks 0, 1, and 2, followed by 210 mg every 2 weeks. At each visit, patients will be evaluated for change in sPGA (Physician's Global Assessment), PASI score, and any signs or symptoms of adverse events. Laboratory screening will include tests for tuberculosis and neutropenia. After completion of the 16-week trial, patients may desire to continue treatment with brodalumab. Efforts will be made to provide drug to these study patients, including those who do not have insurance.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Evaluate the Safety and Efficacy of Brodalumab in Subjects With Moderate to Severe Plaque Psoriasis Who Have Failed IL-17A Therapies
• Actual Study Start Date: Oct 31, 2017
• Actual Primary Completion Date: Aug 18, 2018
• Actual Study Completion Date: Aug 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Brodalumab Brodalumab (210 mg) via subcutaneous injection using prefilled syringes	Drug: Brodalumab; Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.; Other Names: Siliq

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Physician's Global Assessment (sPGA) Score 0 or 1 [16 weeks]

   Number of patients achieving a score of "0-clear" or "1-almost clear" in the sPGA score after 16 weeks of treatment to measure efficacy. Static Physician Global Assessment (sPGA) - 3 categories induration, erythema, and scaling, scored 0-4, these 3 categories averaged giving total score from 0-4, with higher score indicating more symptoms.

Secondary Outcome Measures

1. Number of Participants With Psoriasis Area and Severity Index (PASI) Score Improvement [16 weeks]

   PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). Number of participants with 75%, 90%, and 100% reduction in the PASI score, respectively, PASI-75, PASI-90, and PASI-100 who completed the trial at week 16.

2. Number of Adverse Events [16 weeks]

   Number of adverse events as a measure of safety

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male or female subject at least 18 years of age

• Subject is able to provide written informed consent and comply with the requirements of this study protocol.

• Have both a sPGA score of ≥3 and BSA ≥ 5% prior to randomization.

• Subjects who are women of childbearing potential must have a negative urine pregnancy test at screening and must be practicing an adequate, medically acceptable method of birth control for at least 30 days before Day 0 and at least 6 months after the last study drug administration. Acceptable methods of birth control include intrauterine device (IUD); oral, transdermal, implanted or injected hormonal contraceptives (must have been initiated at least 1 month before entering the study); tubal ligation; abstinence and barrier methods with spermicide. Otherwise, if not of childbearing potential, subjects must: have a sterile or vasectomized partner; have had a hysterectomy, a bilateral oophorectomy or be clinically diagnosed infertile; or be in a menopausal state for at least a year.

• Tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) negative at the time of screening, or if patient has a history of positive PPD or QuantiFERON, he/she has initiated or completed the appropriate prophylaxis.

• Subject is judged to be in good general health as determined by the principal investigator based upon the results of medical history and laboratory profile.

• Subject has previously failed treatment with an IL-17A agent, secukinumab or ixekizumab, (where available, defined as previous treatment with either drug for at least 3 months without achieving PASI-75 response or a 50% loss of original improvement).

• Last administration of secukinumab or ixekizumab ≥ 28 days prior to Baseline.

Exclusion Criteria:

• Have predominantly pustular, erythrodermic, and/or guttate forms of psoriasis.

• History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) at Screening. Subjects with a positive or indeterminate PPD or QFT test may participate in the study if a full tuberculosis work up (according to local practice/guidelines) is completed within 12 weeks prior to randomization and establishes conclusively that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated at least for 4 weeks prior to randomization and the course of prophylaxis is planned to be completed.

• Subjects with a history of HIV, or history of positive HCV or HBV

• Use of any of the following therapies within 4 weeks prior to Baseline (Visit 2): systemic non-biologic psoriasis therapies (including, but not limited to): psoralens and ultraviolet A (PUVA) therapy, cyclosporine, methotrexate, azathioprine, corticosteroids, apremilast, tofacitinib, oral retinoids, mycophenolate mofetil, sirolimus; 1, 25 dihydroxyvitamin D analogs; or phototherapy (including UVB or self-treatment with tanning beds or therapeutic sunbathing) or topical psoriasis therapy with psoralens.

• Use of topical corticosteroid preparations, topical calcineurin inhibitors, or other topical preparations with immunomodulatory properties within 2 weeks prior to Baseline (Visit 2).

• Use of any investigational drug or any systemic drug for psoriasis within four weeks prior to Baseline (Visit 2).

• Serious concomitant illness that could require the use of systemic corticosteroids or otherwise interfere with the patient's participation in the trial.

• Clinically important deviation as judged by the investigator (such WBC< 3) from normal limits in physical examination, vital sign measurements, clinical laboratory tests results, not associated with a chronic, well-controlled medical condition.

• Any active live-vaccines 3 months prior to baseline and throughout the study.

• Have a current or history of lymphoproliferative disease within 5 years prior to Baseline (Visit 2); or have current or history of any malignant disease within 5 years prior to Baseline (Visit 2).

• History of suicide attempt, or are clinically judged by investigator to be at risk of suicide.

• History of Crohn's disease.

• Had a serious infection, been hospitalized, or received IV antibiotics for an infection, within 12 weeks prior to Baseline (Visit 2).

• Known immunodeficiency, or history of infection typical of an immunocompromised host.

• At screening, have a neutrophil count <1500 cells/uL.

• At screening, have a lymphocyte count <800 cells/uL.

• At screening, have a platelet count <100,000 cells/uL.

• At screening, have a total white blood count (WBC) < 3000 cells/uL.

• At screening, have a hemoglobin <8.5 g/dL.

• Have donated >450 mL of blood within 4 weeks prior to screening (Visit 1), or intend to donate blood during the course of the study.

• Women who are lactating or breastfeeding.

• Any other condition that precludes the patient from following and completing the protocol, in the opinion of the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
2	Baylor College of Medicine	Houston	Texas	United States	70030

Sponsors and Collaborators

• Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Mark Lebwohl, MD, Icahn School of Medicine at Mount Sinai

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 12, 2017

More Information

Publications

None provided.

• Responsible Party: Mark Lebwohl, Professor, Icahn School of Medicine at Mount Sinai
• ClinicalTrials.gov Identifier: NCT03403036
• Other Study ID Numbers: GCO 17-1581
• First Posted: Jan 18, 2018
• Last Update Posted: Mar 10, 2021
• Last Verified: Feb 1, 2021

• 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.: Yes
• Keywords provided by Mark Lebwohl, Professor, Icahn School of Medicine at Mount Sinai: Psoriasis; brodalumab
• Additional relevant MeSH terms: Psoriasis; Brodalumab

Study Results

Participant Flow

Recruitment Details	41 patients screened with 39 meeting all eligibility requirements. Patients with moderate-to-severe psoriasis were recruited from 3 sites.

Arm/Group Title	Brodalumab
Arm/Group Description	Brodalumab (210 mg) via subcutaneous injection using prefilled syringes given at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
Period Title: Overall Study
STARTED	39
COMPLETED	34
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Brodalumab
Arm/Group Description	Brodalumab (210 mg) via subcutaneous injection using prefilled syringes given at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
Overall Participants	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.74 (2.64)
Sex: Female, Male (Count of Participants)
Female	14 35.9%
Male	25 64.1%
Race and Ethnicity Not Collected (Count of Participants)
Baseline PASI (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.36 (2.24)
Baseline sPGA (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.41 (0.08)
Number of participants who failed Secukinumab (Count of Participants)
Count of Participants [Participants]	16 41%
Number of participants who failed Ixekizumab (Count of Participants)
Count of Participants [Participants]	19 48.7%
Number of participants who failed both Secukinumab and Ixekizumab (Count of Participants)
Count of Participants [Participants]	4 10.3%
Number of previously failed biologics (biologic medications) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [biologic medications]	2.23 (0.29)

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Physician's Global Assessment (sPGA) Score 0 or 1
Description	Number of patients achieving a score of "0-clear" or "1-almost clear" in the sPGA score after 16 weeks of treatment to measure efficacy. Static Physician Global Assessment (sPGA) - 3 categories induration, erythema, and scaling, scored 0-4, these 3 categories averaged giving total score from 0-4, with higher score indicating more symptoms.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab
Arm/Group Description	Brodalumab (210 mg) via subcutaneous injection using prefilled syringes given at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
Measure Participants	34
Count of Participants [Participants]	24 61.5%

2. Secondary Outcome

Title	Number of Participants With Psoriasis Area and Severity Index (PASI) Score Improvement
Description	PASI combines the assessment of the severity of lesions and the area affected into a single score in the range 0 (no disease) to 72 (maximal disease). Number of participants with 75%, 90%, and 100% reduction in the PASI score, respectively, PASI-75, PASI-90, and PASI-100 who completed the trial at week 16.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab
Arm/Group Description	Brodalumab (210 mg) via subcutaneous injection using prefilled syringes given at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
Measure Participants	34
PASI-75	26 66.7%
PASI-90	17 43.6%
PASI-100	11 28.2%

3. Secondary Outcome

Title	Number of Adverse Events
Description	Number of adverse events as a measure of safety
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Brodalumab
Arm/Group Description	Brodalumab (210 mg) via subcutaneous injection using prefilled syringes given at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
Measure Participants	39
Number [events]	6

Adverse Events

Time Frame	16 weeks
Arm/Group Title	Brodalumab
Arm/Group Description	Brodalumab (210 mg) via subcutaneous injection using prefilled syringes given at Weeks 0, 1, 2, and every 2 weeks thereafter through and including Week 16.
All Cause Mortality
	Brodalumab
	Affected / at Risk (%)	# Events
Total	0/39 (0%)
Serious Adverse Events
	Brodalumab
	Affected / at Risk (%)	# Events
Total	0/39 (0%)
Other (Not Including Serious) Adverse Events
	Brodalumab
	Affected / at Risk (%)	# Events
Total	6/39 (15.4%)
Endocrine disorders
Pre-Diabetes	1/39 (2.6%)	1
Eye disorders
Corneal Ulcer	1/39 (2.6%)	1
Immune system disorders
Allergic Sinusitis	1/39 (2.6%)	1
Infections and infestations
Tooth Abscess	1/39 (2.6%)	1
Musculoskeletal and connective tissue disorders
Sciatica	1/39 (2.6%)	1
Skin and subcutaneous tissue disorders
Folliculitis	1/39 (2.6%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.