Clinical trial NCT01726933: LAS41008 in Moderate to Severe Chronic Plaque Psoriasis
Official title: A Multi-center, Randomized, Double-blind, Three-arm, 16 Week, Adaptive Phase III Clinical Study to Investigate the Efficacy and Safety of LAS41008 vs LASW1835 and vs Placebo in Patients With Moderate to Severe Chronic Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plaque Psoriasis
Keywords: psoriasis, systemic treatment
Lead sponsor: Almirall, S.A.
Sponsor class: INDUSTRY
Collaborators: name: Almirall Hermal GmbH
name: Harrison Clinical Research
First posted: 2012-11-15
Enrollment: 839
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: The aim of the study is to evaluate the efficacy and safety of LAS41008 in comparison to active control and placebo in patients with moderate to severe chronic plaque psoriasis


Eligibility criteria: Inclusion Criteria:

1. Signed and personally dated written informed consent
2. Male / female
3. Aged 18 years or older
4. With a diagnosis of chronic plaque psoriasis for at least 12 months before enrollment in the study
5. With the severity of psoriasis defined as moderate to severe, as reflected in meeting all the following criteria:

   * PASI \> 10
   * BSA (body surface area) \> 10 %
   * PGA moderate to severe
6. With general good health, or a stable medical condition not considered likely to interfere with the conduct of the clinical study, as determined by the investigator based upon results of medical history, laboratory results and physical examination
7. Prior therapy with systemic drugs for psoriasis or naïve to systemic treatment but identified as a candidate for systemic treatment.
8. With a complete record of at least 12 months of other previous topical and systemic treatments, if any
9. Adhering to the following wash-out periods Topical treatment Wash-out Period Corticosteroids Vitamin A analogues Vitamin D analogues Anthracene derivatives Tar Salicylic acid preparations 2 weeks Systemic treatment Biologics with antipsoriatic activity 3 months Conventional systemic antipsoriatic drugs and phototherapy 1 month Immunosuppressive medication (if not covered by any of the above treatments) Cytostatics 6 months Medications with known harmful influences on the kidneys 5 x halftime
10. For females of child-bearing potential: a negative serum pregnancy test at screening and willing to use highly effective methods of birth control during the study period and for 60 days after the last dose of investigational product. Additionally they must agree to have pregnancy tests while on study medication. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some IUDs, sexual abstinence or vasectomized partner. Female patients will be considered to be of childbearing potential unless surgically sterilized by hysterectomy or bilateral tubal ligation, or post-menopausal for at least two years.
11. Males (including those who have had vasectomy) must agree to use barrier contraception while on study medication
12. Willing to keep sun exposure reasonably constant and not to use tanning booths or other UV light sources for the duration of the trial

Exclusion Criteria:

1. For females: pregnant or lactating
2. With a diagnosis of guttate, erythrodermic or pustular psoriasis
3. With a hematological abnormality as follows: platelet count \< 100,000/mm3, WBC count \< 3,000 cells/ mm3, lymphocyte count \< 1.000/µl, hemoglobin, hematocrit, or red blood cell count outside 30 % of the upper or lower limits of normal for the lab
4. With a history of malignancies except for non melanoma skin cancer
5. Suffering from significant gastrointestinal problems (ulcers, diarrhea, etc.)
6. Known to have significant renal impairment
7. Are detected to have abnormal liver enzymes \>2x the upper limit of the normal range
8. With active infectious disease
9. On systemic therapy with drugs that may interfere with the investigational products taken within the defined wash-out period
10. With a history of alcohol or drug abuse
11. Known HIV-positive status or suffering from any other immunosuppressive disease
12. Known to be hypersensitive to ingredients of the investigational products
13. Previous enrolled in this study or participating in any other drug investigational trial within the 30 days (or five half-lives whichever is longer) prior to enrolment.
14. Not willing to give consent for transmission of personal "pseudonymised" data
15. Unable to comply with the requirements of the study or who in the opinion of the investigator should not participate in the study

Primary outcomes:
measure: PASI 75
timeFrame: 16 weeks
measure: Physician Global Assessment, PGA
timeFrame: 16 weeks
Secondary outcomes:
measure: Body Surface Area, BSA
timeFrame: 16 weeks
measure: Dermatological Life Quality Index, DLQI
timeFrame: 16 weeks
measure: PASI 75
timeFrame: week 3 and 8
measure: PGA
timeFrame: week 3 and 8
measure: Adverse events
timeFrame: ongoing
Other outcomes:
measure: Patient Benefit Index, PBI
timeFrame: week 16
Locations:
city: Various
country: Austria
facility: Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows: Almirall Investigative Site
city: Various
country: Germany
facility: Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows: Almirall Investigative Site
city: Various
country: Netherlands
facility: Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows: Almirall Investigative Site
city: Various
country: Poland
facility: Investigatives site names will not be disclosed to avoid competitive information. Specify at least one site as follows:Almirall Investigative Site #
Study officials:
affiliation: University Medical Center, Schleswig-Holstein, Department of Dermatology, Schittenhelmstr. 7, 24105 Kiel, Germany
name: Ulrich Mrowietz, MD, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Warren RB, Barker JNW, Van de Kerkhof P, Reich K, Mrowietz U. Switching from a fumaric acid ester mixture to dimethylfumarate monotherapy in psoriasis. J Eur Acad Dermatol Venereol. 2019 Oct;33(10):e352-e353. doi: 10.1111/jdv.15644. Epub 2019 May 10. No abstract available.