Clinical trial NCT02949388: Efficacy and Safety of Prurisol Administered Orally for Active Moderate to Severe Chronic Plaque Psoriasis
Official title: A Randomized, Double Blind, Parallel Group, Placebo-controlled Trial to Study the Efficacy and Safety of Two Oral Doses of Prurisol Administered Twice Daily for Twelve Weeks to Subjects With Moderate to Severe Chronic Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Stable Plaque Psoriasis
Lead sponsor: Innovation Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2016-10-31
Enrollment: 199
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed as a randomized, double blind, parallel group, placebo-controlled trial to study the efficacy and safety of two oral doses of Prurisol administered twice daily for twelve weeks to subjects with moderate to severe chronic plaque psoriasis.

Detailed description: This study is designed as a randomized, double blind, parallel group, placebo-controlled trial to study the efficacy and safety of two oral doses of Prurisol administered twice daily for twelve weeks to subjects with moderate to severe chronic plaque psoriasis.

Approximately 189 study participants will be enrolled. Subjects will be randomly assigned to one of three treatment groups in a 3:3:1 randomization ratio, respectively.

* Group A (n=81): Prurisol 150 mg bid
* Group B (n=81): Placebo
* Group C (n=27): Prurisol 200 mg bid Outpatient subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy will be recruited to the study. Study participants are required to have a Psoriasis Area and Severity Index (PASI) score ≥ 12, body surface area involvement ≥ 10%, and a static Physician's Global Assessment (sPGA) of moderate or severe (score of 3 or 4).

A subject studied under this clinical protocol will commence with a screening period of up to 4 weeks, a treatment period of 12 weeks, and a follow-up period of 4 weeks ending with an End of Study evaluation.

During treatment, subjects will return to the study center every 2 weeks. Efficacy assessments, including physician and patient rated endpoints, will be measured throughout the study. Safety and tolerability will be assessed by ascertainment of AEs and results of clinical laboratory testing, vital signs assessments, and need for concomitant medications.

At a subset of sites, blood samples for determination of plasma concentrations of Prurisol (abacavir glycolate) and abacavir, it's metabolite, will be obtained from subjects who consent to provide these samples. At selected sites, for those subjects consenting to photography, standardized digital photographs will be obtained for illustrative purposes.

Eligibility criteria: Inclusion Criteria:

1. Evidence of a personally signed and dated written informed consent to participate in the clinical study
2. Male or non-pregnant female adults at least 18 years of age at time of informed consent
3. Chronic plaque-type psoriasis diagnosed for at least 6 months prior to baseline (at time of first study dose)
4. Moderate to severe plaque psoriasis as defined at baseline by:

   1. PASI score of 12 or greater, and
   2. Static PGA score of moderate (3) or severe (4), and
   3. Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater
5. Candidate for systemic therapy or phototherapy
6. Willing to limit ultraviolet light exposure from sunbathing, use of tanning booths, prolonged outdoor exposure, or from other UV light sources during the study.
7. Willing and able to comply with scheduled visits, study assessments and l laboratory tests, and other study procedures

Exclusion Criteria:

1. Positive blood test for HLA-B\*5701 allele
2. Currently have forms of psoriasis other than chronic plaque-type, (e.g., guttate, erythrodermic, exfoliative, palmoplantar, pustular), with the exception of nail psoriasis
3. Evidence of drug-induced psoriasis, e.g., a new onset or current exacerbation of psoriasis from beta-blockers, calcium channel inhibitors, antimalarial drugs or lithium
4. Psoriasis flare or rebound within 4 weeks prior to Screening
5. Active inflammatory diseases other than psoriasis that might confound the evaluation of study treatment on signs and symptoms of psoriasis.
6. . Any of the following prohibited treatments that do not meet the specified minimum washout period:

   1. Biologic immunomodulating treatments of brodalumab or ustekinumab within 24 weeks prior to start of study treatment
   2. Biologic immunomodulating treatments such as adalimumab, etanercept, infliximab, ixekizumab, secukinumab or certolizumab pegol within 12 weeks prior to start of study treatment
   3. Systemic immunomodulating treatments other than biologics within 4 weeks prior to start of study treatment, e.g., oral corticosteroids, injectable corticosteroids (intraarticular, intramuscular, cutaneous/subcutaneous or intravenous), methotrexate, cyclosporine, cyclophosphamide, apremilast

      * Inhaled or intranasal corticosteroids with predominantly local effect (e.g., to treat asthma) are allowable
      * Use of corticosteroids in the eye or the ear are allowable
   4. Other systemic treatments for psoriasis within 4 weeks prior to start of study treatment, e.g., retinoids, fumarates

      * Any such treatment used to treat a symptom of psoriasis but not the condition itself (e.g., anti-histamines for pruritus) is not restricted
   5. Photochemotherapy, e.g., Psoralens + UVA phototherapy (PUVA), within 4 weeks prior to start of study treatment
   6. Phototherapy, e.g., UVA, UVB, within 2 weeks prior to start of study treatment
   7. Topical treatments that could affect signs and symptoms of psoriasis within 2 weeks prior to start of study treatment, e.g., corticosteroids, vitamin D analogs, retinoids, pimecrolimus, tacrolimus, tars, keratolytics

      * Allowable exceptions are: low or least potent (Class 6 or 7) topical corticosteroids for use on face, palms, soles, and intertriginous areas only; tar and salicylic acid preparations/shampoos for use on scalp only; bland emollient for use on any body region
7. Past vaccination with live vaccine within 6 weeks prior to start of study treatment, or plans for administration during the study
8. Any investigational or experimental therapy or procedure or participation in any interventional trial within 4 weeks or 5 half-lives (whichever is longer) prior to start of study treatment
9. Women of child-bearing potential who are not using reliable means of contraception, e.g., abstinence, surgical sterilization (hysterectomy and/or bilateral oophorectomy or partner vasectomy) or tubal ligation, double barrier method, oral/ injected/ implanted/ transdermal hormonal contraception, intrauterine device or intrauterine system, throughout study participation, and for 4 weeks after the end of treatment
10. Women of child-bearing potential who are pregnant or nursing (lactating), or planning a pregnancy while participating in the study
11. History of any ongoing, chronic or recurrent infectious disease (with the exception of episodic herpes labialis and herpes genitalis, and vaginal yeast infections)
12. Evidence of tuberculosis infection as defined by a positive QuantiFERON®-TB Gold In-Tube test (QFT-G) at Screening, or subjects with an indeterminate QFT-G test result with any retest result as indeterminate or positive
13. History of either untreated or incompletely treated latent or active tuberculosis infection
14. Ongoing or recent history of any non-psoriatic uncontrolled (in the Investigator's medical opinion) systemic disease, including, but not limited to renal, hepatic, hematologic, gastrointestinal, endocrine, metabolic, pulmonary, cardiac, neurologic, or psychiatric disease. (e.g., A past or current history of hypertension that is controlled with diet and/or medications is not exclusionary.)
15. History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years with the exception of: basal cell or squamous cell carcinoma or actinic keratoses that have been treated or excised with no evidence of recurrence in the past 12 weeks; cervical carcinoma in situ or non-invasive malignant colon polyps that have been removed
16. Active systemic infections during the past two weeks (exception: common cold) prior to start of study treatment or any infection that reoccurs on a regular basis
17. Past medical history of infection with HIV, hepatitis B or hepatitis C
18. History of any allergic reaction to any formulation of abacavir
19. Previous treatment with any abacavir-containing product, e.g., Ziagen®, Epzicom®, or Trizivir®
20. Previous participation in a clinical study of Prurisol
21. Presence of any medical or psychiatric condition that, in the Investgator's opinion, makes it unlikely that the requirements of the protocol will be completed
22. History of alcohol or substance abuse, unless in full remission for more than 6 months prior to start of study treatment
23. Electrocardiogram (ECG) obtained at Screening visit which shows medically relevant abnormalities which may affect subject safety or interpretation of study results
24. Observed clinical laboratory values/abnormalities during Screening that show any one or more of the following:

    1. Screening total white blood cell (WBC) count \<2.5 x 10\^9/L, or platelets \<100 x 10\^9/L or neutrophils \<1.2 x 10\^9/L or hemoglobin \<8.5 g/dL
    2. Screening serum creatinine level exceeding 2.0 mg/dL (176.8 µmol/L)
    3. Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \> 2 x ULN
25. Any other severe acute or chronic medical or psychiatric condition or test abnormality(ies) that, in the Investigator's opinion, puts the subject at significant risk, could confound the study results, or may interfere significantly with the subject's participation in the study

Primary outcomes:
measure: Proportion of participants achieving at least a 75% reduction from baseline in PASI score (PASI75) at Week 12
timeFrame: 12 Weeks
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: 16 Weeks
Secondary outcomes:
measure: Proportion of subjects achieving a static Physician Global Assessment (sPGA) score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline
timeFrame: 16 Weeks
measure: PASI75 response at time points through Week 16
timeFrame: 16 Weeks
measure: The actual and change from baseline in patient-reported itch severity score
timeFrame: 16 weeks
measure: Assessment of patient-reported quality of life by the Dermatology Life Quality Index (DLQI)
timeFrame: 16 Weeks
measure: Assessment of patient-reported quality of life by the Short Form-36 Health Survey (version 2, acute form)
timeFrame: 12 Weeks
measure: Assessment of patient-reported quality of life by the Euro-Qol 5 Dimensions Health State Profile
timeFrame: 12 Weeks
measure: Assessment of Patient Satisfaction with Study Treatment (PSST)
timeFrame: 12 Weeks
measure: Plasma concentrations of Prurisol
timeFrame: 4 Weeks
measure: Plasma concentrations of abacavir
timeFrame: Timeframe: 4 weeks
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Study Site
state: Arizona
city: Hot Springs
country: United States
facility: Study Center
state: Arkansas
city: Rogers
country: United States
facility: Clinical Study Site
state: Arkansas
city: Los Angeles
country: United States
facility: Study Center
state: California
city: Los Angeles
country: United States
facility: Study Site
state: California
city: Murrieta
country: United States
facility: Clinical Study Site
state: California
city: Oceanside
country: United States
facility: Clinical Study Site
state: California
city: Sherman Oaks
country: United States
facility: Study Site
state: California
city: Denver
country: United States
facility: Study Site
state: Colorado
city: Denver
country: United States
facility: Clinical Study Site
state: Colorado
city: Port Orange
country: United States
facility: Study Site
state: Florida
city: Tampa
country: United States
facility: Clinical Study Site
state: Florida
city: Savannah
country: United States
facility: Study Site
state: Georgia
city: Arlington Heights
country: United States
facility: Study Center
state: Illinois
city: South Bend
country: United States
facility: Clinical Study Site
state: Indiana
city: Overland Park
country: United States
facility: Study Center
state: Kansas
city: Louisville
country: United States
facility: Study Site
state: Kentucky
city: Clarkston
country: United States
facility: Clinical Study Site
state: Michigan
city: Clinton Township
country: United States
facility: Clinical Study Site
state: Michigan
city: Saint Louis
country: United States
facility: Clinical Study Site
state: Missouri
city: Las Vegas
country: United States
facility: Study Site
state: Nevada
city: Portsmouth
country: United States
facility: Clinical Study Site
state: New Hampshire
city: Berlin
country: United States
facility: Clinical Study Site
state: New Jersey
city: New York
country: United States
facility: Clinical Study Site
state: New York
city: Portland
country: United States
facility: Clinical Study Site
state: Oregon
city: Johnston
country: United States
facility: Study Site
state: Rhode Island
city: Austin
country: United States
facility: Study Center
state: Texas
city: Houston
country: United States
facility: Clinical Study Site
state: Texas
city: Pflugerville
country: United States
facility: Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Clinical Study Site
state: Texas
city: San Antonio
country: United States
facility: Study Site
state: Texas
city: Webster
country: United States
facility: Study Site
state: Texas
city: Charlottesville
country: United States
facility: Study Center
state: Virginia
Study officials:
References: