Psoriasis, Psoriasis Vulgaris, Psoriatic Nail
Conditions
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.
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.
Interventions
DRUGApremilast
Sponsors
Celgene
University of Alabama at Birmingham
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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.) |
| Percent 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 100 (0=no pain ; 100 = as severe pain as you can imagine). This outcome measure was completed by subtracting the value at Week 52 from the original value at baseline. This was a decrease, which was then divided by the baseline value and multiplied by 100. |
| Pain Change in Psoriatic Arthritis (PsA) 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 0 to 100 (0= no pain ; 100 = as severe pain as you can imagine).This outcome measure was completed by subtracting the value at Week 52 from the original value at baseline. This was a decrease, which was then divided by the baseline value and multiplied by 100. |
| 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.) |
| 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.) |
| Percentage Change From Baseline in mNAPSI. | 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.). For week 36 we averaged each participants mNAPSI percent change from baseline to week 36. We did the same thing for week 52 |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Study Group Open-label drug administration group. No comparator.
Apremilast | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Study Group |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 12 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 10 / 12 |
| serious Total, serious adverse events | 1 / 12 |
Outcome results
Primary
Mean Percent Change of mNAPSI (Modified Nail Area Psoriasis Severity Index) at Week 36 Compared to Baseline for All Nails.
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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Study Group | Mean Percent Change of mNAPSI (Modified Nail Area Psoriasis Severity Index) at Week 36 Compared to Baseline for All Nails. | 64.1 percentage of reduction in mNAPSI score |
p-value: 0.05t-test, 2 sided
Secondary
Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline.
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
Population: Participants lost to follow-up
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Study Group | Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. | Week 12 | 53.9 percentage of reduction in mNAPSI score |
| Study Group | Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. | Week 24 | 65.1 percentage of reduction in mNAPSI score |
| Study Group | Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. | Week 36 | 63.8 percentage of reduction in mNAPSI score |
| Study Group | Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. | Week 48 | 57.7 percentage of reduction in mNAPSI score |
| Study Group | Mean Percent Change in mNAPSI of Target Nail at Weeks 12, 24, 36, 48, and 52 Compared to Baseline. | Week 52 | 75.8 percentage of reduction in mNAPSI score |
Secondary
Pain Change in Psoriatic Arthritis (PsA) Symptoms at Week 52 Compared to Baseline, in Patients Who Self-identify as Having Psoriatic Arthritis at Baseline.
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 0 to 100 (0= no pain ; 100 = as severe pain as you can imagine).This outcome measure was completed by subtracting the value at Week 52 from the original value at baseline. This was a decrease, which was then divided by the baseline value and multiplied by 100.
Time frame: 52 weeks
Population: Participants lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Pain Change in Psoriatic Arthritis (PsA) Symptoms at Week 52 Compared to Baseline, in Patients Who Self-identify as Having Psoriatic Arthritis at Baseline. | -28.97 percentage change in PsA pain symptoms | Standard Deviation 3.2 |
Secondary
Percentage Change From Baseline in mNAPSI.
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.). For week 36 we averaged each participants mNAPSI percent change from baseline to week 36. We did the same thing for week 52
Time frame: 36 and 52 weeks
Population: Participants were lost to follow-up.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Study Group | Percentage Change From Baseline in mNAPSI. | Week 36 | 17.1 percent change |
| Study Group | Percentage Change From Baseline in mNAPSI. | Week 52 | 30 percent change |
Secondary
Percent Change in Patient Reported Nail Pain, as Based on the Nail Pain VAS Score, at Week 52 Compared to Baseline Score.
Nail pain VAS is a subjective survey completed by patients. Scores range from 0 to 100 (0=no pain ; 100 = as severe pain as you can imagine). This outcome measure was completed by subtracting the value at Week 52 from the original value at baseline. This was a decrease, which was then divided by the baseline value and multiplied by 100.
Time frame: 52 weeks
Population: Participants were lost to follow-up.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Study Group | Percent Change in Patient Reported Nail Pain, as Based on the Nail Pain VAS Score, at Week 52 Compared to Baseline Score. | -50.42 percent change in nail pain score | Standard Deviation 2.26 |
Secondary
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.
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
Population: Data was not collected for this outcome.
Secondary
Proportion of Patients Achieving mNAPSI of 0 in All Fingernails at Weeks 36 and 52.
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
Population: This was not measured.
Secondary
Safety Adverse Effects Will be Assessed at Each Visit
Patients will be asked about illnesses and other health related events while taking part in the study.
Time frame: 52 weeks
Population: All participants were asked about illnesses and other health related events during their time in the study. All were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Nausea | 5 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Abdominal pain | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Acne | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Acute gout | 2 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Acute eye vision loss | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Bronchitis | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Diarrhea | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Emesis | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Headache | 2 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Increased bowel movement | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Psoriasis flare | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Wrist skin infection | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Salmonella | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Upper respiratory infections | 3 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Viral Gastroenteritis | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Worsened Asthma | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Dyspepsia | 1 Participants |
| Study Group | Safety Adverse Effects Will be Assessed at Each Visit | Acute stroke | 1 Participants |