An Investigator Initiated Open Label Study Evaluating the Efficacy and Tolerability of Oral Apremilast for the Treatment of Nail Psoriasis

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03022617
• Collaborator: Celgene (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Duration (Months): 68.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Psoriasis vulgaris is a common inflammatory condition of the skin that results in scaly red itchy plaques. In addition to affecting the skin, psoriasis can also cause disease in the finger and toe nails. The most characteristic nail findings associated with nail psoriasis are nail pitting, onycholysis with a rim of erythema, and oil spots. Because nail psoriasis causes a substantial disease burden for patients, it is critical that safe and effective treatments are found for this specific type of psoriasis. Unfortunately, nail psoriasis is often difficult to treat.

Apremilast is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4) that is FDA approved for the treatment of psoriasis and psoriatic arthritis. Apremilast has shown promising results for treating psoriatic arthritis and nail disease; however more data is needed regarding its effect on nail psoriasis (Kavanaugh, et al). We hypothesize that apremilast will prove to be highly effective in treating nail psoriasis. We propose to conduct an open label clinical trial to investigate the efficacy and tolerability of apremilast in treating nail psoriasis, where we will follow the package insert guidelines for treating patients with apremilast.

Condition or Disease	Intervention/Treatment	Phase
Psoriatic Nail; Psoriasis Vulgaris; Psoriasis	Drug: Apremilast	Phase 4

Detailed Description

Psoriasis vulgaris is a common inflammatory condition of the skin that results in scaly red itchy plaques. In addition to affecting the skin, psoriasis can also cause disease in the finger and toe nails. Nail psoriasis is a chronic disease and can present with the following clinical findings: splinter hemorrhage, leukonychia, red spots in the lunula, nail pitting, nail plate crumbling, hyperkeratosis, and/or nail plate separation from the nail bed. The most characteristic nail findings associated with nail psoriasis are nail pitting, onycholysis with a rim of erythema, and oil spots. Special interest will be paid to identifying these particular nail findings in patients, however all potential nail psoriasis symptoms will be assessed in patients in this study. Due to the highly visible nature of disease in the fingernails, nail psoriasis often results in a substantial deleterious effect on a patient's quality of life. Patients also can have significant pain and disability due to nail psoriasis.

Psoriasis patients who have nail involvement are known to have more severe psoriasis disease and diminished quality of life when compared to psoriasis patients without nail disease. Patients with nail psoriasis often also have psoriatic arthritis, and untreated psoriatic arthritis is known to lead to joint destruction with potentially severe morbidity. Nail psoriasis has a reported incidence of 80 to 90% (Jiaravuthiasan, et al). Because nail psoriasis causes a substantial disease burden for patients, it is critical that safe and effective treatments are found for this specific type of psoriasis. Unfortunately, nail psoriasis is often difficult to treat.

Apremilast is an orally available small molecule inhibitor of phosphodiesterase 4 (PDE4) that is FDA approved for the treatment of psoriasis and psoriatic arthritis. PDE4 is one of the main phosphodiesterases expressed in immune cells, and its inhibition by apremilast is thought to increase cyclic adenosine monophosphate and thereby decrease the inflammatory response. Specifically, apremilast is believed to down regulate pro-inflammatory cytokines including TNF-α, (Tumor necrosis Factor) IL-23 (Interleukin), IL-17, and others.

Apremilast has shown promising results for treating psoriatic arthritis and nail disease; however more data is needed regarding its effect on nail psoriasis (Kavanaugh, et al). We hypothesize that apremilast will prove to be highly effective in treating nail psoriasis. We propose to conduct an open label clinical trial to investigate the efficacy and tolerability of apremilast in treating nail psoriasis, where we will follow the package insert guidelines for treating patients with apremilast.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Sep 1, 2020
• Anticipated Study Completion Date: Sep 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Study Group Open-label drug administration group. No comparator.	Drug: Apremilast

Outcome Measures

Primary Outcome Measures

1. Mean Percent Change of mNAPSI (Modified Nail Area Psoriasis Severity Index) at Week 36 Compared to Baseline for All Nails. [36 weeks]

   mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)

Secondary Outcome Measures

1. Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. [12, 24, 36, 48, and 52 weeks]

   The target nail will be defined as the nail that has the highest mNAPSI singe nail score at baseline. This nail will remain the target nail for the remainder of the study. mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)

2. Proportion of Patients Achieving mNAPSI of 0 in All Fingernails at Weeks 36 and 52. [36 and 52 weeks]

   mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)

3. Change in Patient Reported Nail Pain, as Based on the Nail Pain VAS Score, at Week 52 Compared to Baseline Score. [52 weeks]

   Nail pain VAS is a subjective survey completed by patients. Scores range from 0 to 10.

4. Pain Change in Psoriatic Arthritis Symptoms at Week 52 Compared to Baseline, in Patients Who Self-identify as Having Psoriatic Arthritis at Baseline. [52 weeks]

   Symptoms will be assessed using a visual analogue scale (VAS) for reporting psoriatic arthritis pain, which is a subjective survey that patients will complete on a scale of 1 to 10.

5. Safety Adverse Effects Will be Assessed at Each Visit [52 weeks]

   Patients will be asked about illnesses and other health related events while taking part in the study.

6. Proportion of Patients Achieving a mNAPSI 75 Response, as Defined by 75% or Greater Reduction Over Baseline in mNAPSI Score at Weeks 12, 24, 36, 48, and 52 for the Target Fingernail. [12, 24, 36, 48, and 52 weeks]

   The target nail will be defined as the nail that has the highest mNAPSI singe nail score at baseline. This nail will remain the target nail for the remainder of the study. mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)

7. Mean Change in the Total Number of Nails Involved Assessed at Weeks 36 and 52 Compared to Baseline. [36 and 52 weeks]

   Health care providers to assess number of nails involved.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• • Patients older than 18

• Give written informed consent prior to any study procedures being conducted, and candidates will authorize the release and use of protected health information (PHI)

• Be willing and consent to having photos taken of their fingernails

• Diagnosis of chronic plaque psoriasis that has been present for at least 6 months prior to baseline

• Plaque psoriasis involving at least 5% of the patient's body surface area

• Nail psoriasis in at least one finger nail with a mNAPSI of 5 or greater

• A Nail Pain VAS score of 4 or higher. The Nail Pain VAS will assess the severity of pain linked to the nail disease.

• Must have discontinued all systemic therapies for the treatment of psoriasis or psoriatic arthritis at least 4 weeks or 5 half-lives, and biologics 2 months or 5 half-lives (whichever is longer) prior to baseline visit

• Must have discontinued all topical therapies for the treatment of psoriasis at least 2 weeks prior to baseline visit

• Subjects must have discontinued UV therapy at least 2 weeks prior to baseline and PUVA (psoralen ultraviolet light therapy) at least 4 weeks prior to baseline.

• Subjects must be in good general health without significant uncontrolled comorbidities, other than psoriasis, as determined by the investigator based on exam findings, medical history, and clinical laboratories. Patients with stable mild renal insufficiency are eligible for enrolling in this trial.

• Females of childbearing potential must use an approved birth control method while receiving treatment and for 28 days following the last dose of apremilast, and there must be a documented negative pregnancy tests prior to initiating treatment. Approved birth control methods include hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring), intrauterine device, partners vasectomy, or male or female condoms that are not made of natural materials plus a diaphragm with spermicide, cervical cap with spermicide, or a contraceptive sponge with spermicide. Females not of child bearing potential are defined as being at least 1 year postmenopausal or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy).

• Male subjects, including those who have had a vasectomy, must use condoms not made of natural materials for the duration of the trial and for at least 28 days after the last dose of apremilast if conception is possible.

Exclusion Criteria:

• • Unable to comply with the protocol (as defined by the Investigator; i.e. drug or alcohol abuse or history of noncompliance)

• Pregnancy or breastfeeding

• Female patients of childbearing potential and male patients who engage in activity where contraception is possible who are unable to use the approved methods of contraception throughout the length of the study and 28 days following the last dose

• Patients who have or have had thoughts of suicide or hurting themselves.

• Patients with prior exposure to apremilast

• Subject has been treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to baseline visit.

• Patients with severe, progressive, or uncontrolled medical or psychiatric disease.

• Concomitant therapy with medications that are strong cytochrome P450 inducers, including rifampin, phenobarbital, carbamazepine, or phenytoin

• Any other dermatologic conditions that prohibit or confound the ability of the investigator to interpret skin and/or nail exam findings.

• Patients who will be unable to avoid the use of systemic steroids, excluding intranasal or inhaled steroids that will be permitted, for the duration of the trial

• Any known hypersensitivity to apremilast

• Any subject who, in the opinion of the investigator, will be uncooperative or unable to comply with duty procedures

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Kirklin Clinic	Birmingham	Alabama	United States	35249

Sponsors and Collaborators

• University of Alabama at Birmingham
• Celgene

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 4, 2017

More Information

Publications

None provided.

• Responsible Party: Boni Elewski, Professor, Chairman, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT03022617
• Other Study ID Numbers: IRB-160720004
• First Posted: Jan 16, 2017
• Last Update Posted: Jul 14, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Psoriasis; Apremilast

Study Results

Participant Flow

Arm/Group Title	Study Group
Arm/Group Description	Open-label drug administration group. No comparator. Apremilast
Period Title: Overall Study
STARTED	12
COMPLETED	6
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	Study Group
Arm/Group Description	Open-label drug administration group. No comparator. Apremilast
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	10 83.3%
>=65 years	2 16.7%
Sex: Female, Male (Count of Participants)
Female	6 50%
Male	6 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	12 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Mean Percent Change of mNAPSI (Modified Nail Area Psoriasis Severity Index) at Week 36 Compared to Baseline for All Nails.
Description	mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)
Time Frame	36 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Study Group
Arm/Group Description	Open-label drug administration group. No comparator. Apremilast
Measure Participants	6
Mean (95% Confidence Interval) [percentage of reduction in mNAPSI score]	64.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Study Group
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.05
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	21.5
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Deviation; Value: 10.89
	Estimation Comments

2. Secondary Outcome

Title	Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline.
Description	The target nail will be defined as the nail that has the highest mNAPSI singe nail score at baseline. This nail will remain the target nail for the remainder of the study. mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)
Time Frame	12, 24, 36, 48, and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Proportion of Patients Achieving mNAPSI of 0 in All Fingernails at Weeks 36 and 52.
Description	mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)
Time Frame	36 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change in Patient Reported Nail Pain, as Based on the Nail Pain VAS Score, at Week 52 Compared to Baseline Score.
Description	Nail pain VAS is a subjective survey completed by patients. Scores range from 0 to 10.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Pain Change in Psoriatic Arthritis Symptoms at Week 52 Compared to Baseline, in Patients Who Self-identify as Having Psoriatic Arthritis at Baseline.
Description	Symptoms will be assessed using a visual analogue scale (VAS) for reporting psoriatic arthritis pain, which is a subjective survey that patients will complete on a scale of 1 to 10.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Safety Adverse Effects Will be Assessed at Each Visit
Description	Patients will be asked about illnesses and other health related events while taking part in the study.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Proportion of Patients Achieving a mNAPSI 75 Response, as Defined by 75% or Greater Reduction Over Baseline in mNAPSI Score at Weeks 12, 24, 36, 48, and 52 for the Target Fingernail.
Description	The target nail will be defined as the nail that has the highest mNAPSI singe nail score at baseline. This nail will remain the target nail for the remainder of the study. mNAPSI is an objective scoring system administered by trained health care providers. Scores range from 0 (no nail disease) to 130 (complete nail involvement in all ten nails.)
Time Frame	12, 24, 36, 48, and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Mean Change in the Total Number of Nails Involved Assessed at Weeks 36 and 52 Compared to Baseline.
Description	Health care providers to assess number of nails involved.
Time Frame	36 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse event data was collected over the entirety of the study, 52 weeks for each participant
Arm/Group Title	Study Group
Arm/Group Description	Open-label drug administration group. No comparator. Apremilast
All Cause Mortality
	Study Group
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Study Group
	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)
Nervous system disorders
Acute Stroke	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Study Group
	Affected / at Risk (%)	# Events
Total	6/12 (50%)
Eye disorders
Acute Eye Vision Loss	1/12 (8.3%)	1
General disorders
Nausea	6/12 (50%)	8
Abdominal Pain	1/12 (8.3%)	1
acute gout	2/12 (16.7%)	2
diarrhea	1/12 (8.3%)	1
Emesis	1/12 (8.3%)	1
Headache	2/12 (16.7%)	2
Increased Bowel Movements	1/12 (8.3%)	1
Salmonella	1/12 (8.3%)	1
Viral Gastroenteritis	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Bronchitis	1/12 (8.3%)	1
Upper Respiratory Infection	3/12 (25%)	3
Worsened Asthma	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
acne	1/12 (8.3%)	1
Psoriasis Flare	1/12 (8.3%)	1
Wrist Skin Infection	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.