An Open-Label, Prospective Study to Assess the Safety and Effectiveness of Adalimumab in Patients With Moderate to Severe Plaque Psoriasis in the Russian Federation

• ClinicalTrials.gov Identifier: NCT01644396
• Recruitment Status: Completed
• First Posted: July 19, 2012
• Results First Posted: September 17, 2014
• Last Update Posted: October 1, 2014
• Sponsor: AbbVie (prior sponsor, Abbott)
• Information provided by (Responsible Party): AbbVie ( AbbVie (prior sponsor, Abbott) )

Study Description

Brief Summary:

This is an open-label study designed to establish the safety and effectiveness of adalimumab in the treatment of moderate to severe plaque psoriasis after 24 weeks of treatment.

Condition or disease	Intervention/treatment	Phase
Moderate to Severe Plaque Psoriasis	Biological: Adalimumab	Phase 4

Detailed Description:

During the treatment period, participants will receive an initial adalimumab 80 milligram (mg) subcutaneous (sc) dose, followed by adalimumab 40 mg sc every other week starting one week after initial dose. Safety and effectiveness assessments will be completed at Baseline, Week 2, Week 4, Week 8, Week 12, Week 16 and Week 24. Participants may discontinue adalimumab treatment at any time during study participation. Participants that end study participation early will have a Premature Discontinuation visit. All participants who do not initiate commercial Humira® will have a follow-up phone call 70 days after the last administration of study drug to obtain information on any new or ongoing Adverse Events (AEs). The 70-day follow-up phone call will not be required for any participant that initiates adalimumab therapy not supplied in the context of the clinical trial after the end of study participation.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Prospective Study to Assess the Safety and Effectiveness of Adalimumab (Humira®) in Patients With Moderate to Severe Plaque Psoriasis in the Russian Federation
• Study Start Date: May 2012
• Actual Primary Completion Date: September 2013
• Actual Study Completion Date: September 2013

Arms and Interventions

Arm	Intervention/treatment
Adalimumab; Participants received an initial adalimumab 80 mg subcutaneous dose, followed by adalimumab 40 mg subcutaneous every other week starting one week after the initial dose for up to 24 weeks.	Biological: Adalimumab; Other Names: ABT-D2E7; Humira

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Achieving a Psoriasis Area and Severity Index 75 (PASI 75) Response at Week 24 [ Time Frame: Baseline and Week 24 ]
   The percentage of participants with a ≥ 75% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.

Secondary Outcome Measures :

1. Percentage of Participants Achieving a Physician's Global Assessment of Clear [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24 ]

   The Physician's Global Assessment (PGA) is a 6-point scale used to measure the severity of disease at the time of the qualified investigator's evaluation of the participant. The degree of overall lesion severity was evaluated using the following categories:

   • 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared;
   • 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal;
   • 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild;
   • 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate;
   • 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked;
   • 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe.

   The percentage of participants achieving a PGA score of clear (0) is reported.

2. Percentage of Participants Achieving a Physician's Global Assessment of Clear or Minimal [ Time Frame: Weeks 2, 4, 8, 12, 16 and 24 ]

   The Physician's Global Assessment (PGA) is a 6-point scale used to measure the severity of disease at the time of the qualified investigator's evaluation of the participant. The degree of overall lesion severity was evaluated using the following categories:

   • 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared;
   • 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal;
   • 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild;
   • 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate;
   • 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked;
   • 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe.

   The percentage of participants achieving a PGA score of clear (0) or minimal (1) is reported.

3. Percentage of Participants Achieving a One Grade Improvement in Physician's Global Assessment (PGA) [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16 and 24 ]

   The PGA is a 6-point scale used to measure the severity of disease at the time of the qualified investigator's evaluation of the participant. The degree of overall lesion severity was evaluated using the following categories:

   • 0: No evidence of scaling, erythema, or plaque elevation, overall score of cleared;
   • 1: Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation, overall score of minimal;
   • 2: Fine scale dominates, light red coloration, mild plaque elevation, overall score of mild;
   • 3: Course scale dominates, moderate red coloration, moderate plaque elevation, overall score of moderate;
   • 4: Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation, overall score of marked;
   • 5: Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation, overall score of severe.

   The percentage of participants achieving a shift from Baseline to a less severe category is reported.

4. Percentage of Participants Achieving a PASI 50 Response [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, and 24 ]
   The percentage of participants with a ≥ 50% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.
5. Percentage of Participants Achieving a PASI 75 Response [ Time Frame: Baseline and Weeks 2, 4, 8, 12, and 16 ]
   The percentage of participants with a ≥ 75% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.
6. Percentage of Participants Achieving a PASI 90 Response [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, and 24 ]
   The percentage of participants with a ≥ 90% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.
7. Percentage of Participants Achieving a PASI 100 Response [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, and 24 ]
   The percentage of participants with a 100% reduction (improvement) in Psoriasis Area and Severity Index (PASI) score from Baseline. PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.
8. Percent Change From Baseline in Psoriasis Area and Severity Index (PASI) Score [ Time Frame: Baseline and Weeks 2, 4, 8, 12, 16, and 24 ]

   PASI is a combination of the intensity of psoriasis, assessed by the erythema (reddening), induration (plaque thickness) and desquamation (scaling) on a scale from no symptoms (0), slight (1), moderate (2), marked (3) or very marked (4), together with the percentage of the area affected, rated on a scale from 0 to 6. PASI scoring is performed at four body areas, the head, arms, trunk, and legs. The total PASI score ranges from 0 to 72. The higher the total score, the more severe the disease.

   Change from Baseline is presented as a percentage of the Baseline value: Post-baseline value - Baseline value / Baseline value * 100. A negative change from Baseline indicates improvement.

9. Percent Change From Baseline in Dermatology Life Quality Index (DLQI) [ Time Frame: Baseline and Weeks 8, 12, and 24 ]
   The DLQI questionnaire asks participants to evaluate the degree that psoriasis has affected their quality of life in the last week, and includes the following parameters: symptoms and feelings, daily activities, leisure activities, work or school activities, personal relationships and treatment related feelings. Participants answer 10 questions on a scale from 0 (not at all) to 3 (very much); the range of the total score is 0 to 30. A score of 21 to 30 means an extremely large effect on the participant's life whereas 0-1 means that the disease has no effect at all. Change from Baseline is presented as a percentage of the Baseline value: Post-baseline value - Baseline value / Baseline value * 100. A negative change from Baseline indicates improvement.
10. Percent Change From Baseline in Nail Psoriasis Severity Index (NAPSI) [ Time Frame: Baseline and Week 24 ]

    NAPSI grades nails for both nail matrix psoriasis and nail bed psoriasis. The most affected fingernail was determined at Baseline and used for the analysis.

    Nail matrix psoriasis consists of any of the following: pitting, leukonychia, red spots in the lunula, or nail plate crumbling. Nail bed psoriasis is the presence or absence of onycholysis, splinter hemorrhages, oil drop (salman patch) discoloration or nail bed hyperkeratosis. Scoring for each is based on the following scale:

    • 0 = none;
    • 1 = present in 1/4 nail quadrants;
    • 2 = present in 2/4 nail quadrants;
    • 3 = present in 3/4 nail quadrants;
    • 4 = present in 4/4 nail quadrants.

    The sum of these two scores is the total score for the nail, and ranges from 0 (no nail psoriasis) to 8 (psoriasis in 4/4 nail quadrants). Change from Baseline is presented as a percentage of the Baseline value, calculated as: Week 24 value - Baseline value / Baseline value * 100. A negative change from Baseline indicates improvement.

Other Outcome Measures:

1. Change From Baseline in Hemoglobin [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
2. Change From Baseline in Hematocrit [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events. The hematocrit measures the volume of red blood cells compared to the total blood volume (red blood cells and plasma).
3. Change From Baseline in Red Blood Cell Count [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
4. Change From Baseline in Blood Cell Counts [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
5. Change From Baseline in Erythrocyte Sedimentation Rate [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
6. Change From Baseline in Alanine Aminotransferase [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
7. Change From Baseline in Aspartate Aminotransferase [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
8. Change From Baseline in Alkaline Phosphatase [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
9. Change From Baseline in Total Bilirubin [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
   Safety variables included laboratory data, vital signs and adverse events.
10. Change From Baseline in Creatinine [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
11. Change From Baseline in Blood Urea Nitrogen (BUN) [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
12. Change From Baseline in Uric Acid [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
13. Change From Baseline in Inorganic Phosphate [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
14. Change From Baseline in Calcium, Sodium and Potassium [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
15. Change From Baseline in Glucose [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
16. Change From Baseline in Albumin [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
17. Change From Baseline in Total Protein [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
18. Change From Baseline in Cholesterol [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
19. Change From Baseline in Triglycerides [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
20. Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
21. Change From Baseline in Urine pH [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
22. Change From Baseline in Urine Specific Gravity [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events. Specific gravity is a measure of the amount of material dissolved in the urine. Specific gravity is the ratio of the density (mass of a unit volume) of a substance to the density (mass of the same unit volume) of a reference substance.
23. Change From Baseline in Blood Pressure [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
24. Change From Baseline in Pulse [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
25. Change From Baseline in Respiratory Rate [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
26. Change From Baseline in Weight [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
27. Change From Baseline in Body Temperature [ Time Frame: Baseline and Week 24 (or Early Termination Visit) ]
    Safety variables included laboratory data, vital signs and adverse events.
28. Number of Participants With Adverse Events (AEs) [ Time Frame: From the first dose of study drug until 70 days after the last dose (up to 33 weeks). ]

    An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment.

    The investigator rated the severity of each AE as either:

    Mild: The AE is transient and easily tolerated; Moderate: The AE causes the participant discomfort and interrupts usual activities.

    Severe: The AE causes considerable interference with usual activities and may be incapacitating or life-threatening.

    A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome.

    Drug-related AEs are those assessed by the investigator as either probably or possibly related.

    Other malignancy excludes lymphoma, hepatosplenic T-cell lymphoma (HSTCL), leukemia, non-melanoma skin cancer (NMSC), and melanoma.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

A patient will be eligible for study participation if he/she meets the following criteria:

1. Male and female patients ≥ 18 years of age.
2. Clinical diagnosis of psoriasis for at least 6 months as determined by patient interview of his/her medical history and confirmation of diagnosis through physical examination by the investigator.
3. Stable plaque psoriasis for at least 2 months before Screening and Baseline visits as determined by patient interview of his/her medical history.
4. Moderate to severe plaque psoriasis defined by ≥ 10% Body Surface Area (BSA) involvement at the Baseline visit.
5. PASI (Psoriasis Area and Severity Index) score ≥ 10 at the Baseline visit.

Exclusion Criteria:

1. Diagnosis of erythrodermic psoriasis, pustular psoriasis, medication induced or medication-exacerbated psoriasis or new onset of guttate psoriasis.
2. Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.

3. Patient who cannot discontinue topical therapies for the treatment of psoriasis such as corticosteroids, vitamin D analogs, or retinoids at least 14 days prior to the Baseline (Week 0) visit and during the study. Participants are allowed to use:

   • Shampoos that contain no corticosteroid;
   • Bland (without beta or alpha hydroxy acids or containing no psoriasis treatment) emollients;
   • Low potency topical corticosteroids on the palms, soles, face, inframammary area, and groin only.
4. Patient who cannot avoid UVB (Ultraviolet-B) phototherapy for at least 14 days prior to the Baseline (Week 0) visit and during the study.
5. Patient who cannot avoid PUVA (psoralen + ultraviolet A) phototherapy for at least 28 days prior to the Baseline (Week 0) visit and during the study.

Contacts and Locations

Locations

Russian Federation

Site Reference ID/Investigator# 67547

Ekaterinburg, Russian Federation, 620076

Site Reference ID/Investigator# 78433

Kazan, Russian Federation, 420012

Site Reference ID/Investigator# 67542

Moscow, Russian Federation, 107076

Site Reference ID/Investigator# 67546

Saratov, Russian Federation, 410028

Site Reference ID/Investigator# 78417

Smolensk, Russian Federation, 214018

Site Reference ID/Investigator# 78413

St. Petersburg, Russian Federation, 190013

Site Reference ID/Investigator# 67545

St. Petersburg, Russian Federation, 194044

Sponsors and Collaborators

AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Martin Okun, MD; AbbVie

More Information

Additional Information:

Related Info 

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01644396
• Other Study ID Numbers: M13-279
• First Posted: July 19, 2012
• Results First Posted: September 17, 2014
• Last Update Posted: October 1, 2014
• Last Verified: September 2014

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):

Moderate to Severe Plaque Psoriasis

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Adalimumab; Anti-Inflammatory Agents; Antirheumatic Agents