Adalimumab in Combination With Topical Treatment (Calcipotriol/Betamethasone) in Subjects With Moderate to Severe Psoriasis and Insufficient Response to Classic Systemic Treatment (BELIEVE)

A Multi-center, Randomized, Vehicle-Controlled Study to Assess the Efficacy and Safety of Adalimumab in Combination With Topical Treatment (Calcipotriol/Betamethasone) in Subjects With Moderate to Severe Psoriasis and Insufficient Response to Classic Systemic Treatment (BELIEVE)

The objective of this study is to assess the efficacy and safety of adalimumab in combination with topical psoriasis treatment, calcipotriol/betamethasone, vs. adalimumab in combination with matching vehicle in subjects with moderate to severe chronic plaque psoriasis.

Study Overview

• Status: Completed
• Conditions: Chronic Plaque Psoriasis
• Intervention / Treatment: Biological: adalimumab; Drug: placebo (vehicle ointment); Drug: Calcipotriol/Betamethasone Ointment

Detailed Description

Additional information regarding sponsors: Abbott GmbH & Co. KG is sponsor for EU member states. Abbott US is sponsor for non-EU member states.

• Study Type: Interventional
• Enrollment (Actual): 730
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
  • Innsbruck, Austria, 6020
  • Salzburg, Austria, 5020
  • Wein, Austria, 1160
  • Wien, Austria, 1030
  • Wien, Austria, 1090
• Belgium
  • Aalst, Belgium, 9300
  • Brugge, Belgium, 8000
  • Brussel, Belgium, 1090
  • Bruxelles, Belgium, 1070
  • Bruxelles, Belgium, 1200
  • Edegem, Belgium, 2650
  • Geel, Belgium, 2440
  • Gent, Belgium, 9000
  • Kortrijk, Belgium, 8500
  • Leuven, Belgium, 3000
  • Liege, Belgium, 4000
  • Mons, Belgium, 7000
• Czech Republic
  • Brno, Czech Republic, 65691
  • Hradec Kralove, Czech Republic, 500 05
  • Prague, Czech Republic, 11000
• Denmark
  • Arhus C, Denmark, 8000
  • Copenhagen, Denmark, 2400
  • Hellerup, Denmark, 2900
  • Herning, Denmark, 7400
• Finland
  • Helsinki HUS, Finland, 00029
  • Jyvaskyla, Finland, 40620
  • Lahti, Finland, 15850
• France
  • Brest Cedex, France, 29609
  • Creteil Cedex, France, 94010
  • Lille Cedex, France, 59037
  • Limoges Cedex, France, 87042
  • Montpellier Cedex 5, France, 34295
  • Nancy, France, 54000
  • Nice Cedex 3, France, 06202
  • Paris Cedex 10, France, 75475
  • Pessac, France, 33604
  • Pierre Benite Cedex, France, 69310
  • Rouen, France, 76031
  • St Etienne Cedex 2, France, 42055
  • Toulouse Cedex 9, France, 31059
• Germany
  • Berlin, Germany, 10117
  • Berlin, Germany, 10827
  • Buchholz Nordheide, Germany, 21244
  • Dresden, Germany, 01307
  • Dresden, Germany, 01067
  • Dusseldorf, Germany, 40225
  • Erlangen, Germany, 91052
  • Frankfurt, Germany, 60590
  • Freiburg, Germany, 79104
  • Gottingen, Germany, 37075
  • Halle Saale, Germany, 06097
  • Hamburg, Germany, 20246
  • Hamburg, Germany, 20354
  • Hannover, Germany, 30449
  • Heidelberg, Germany, 69115
  • Jena, Germany, 07740
  • Kiel, Germany, 24150
  • Koln, Germany, 50924
  • Leipzig, Germany, 04103
  • Magdeburg, Germany, 39120
  • Mainz, Germany, 55101
  • Munchen, Germany, 80337
  • Munster, Germany, 48149
  • Oldenburg, Germany, 26133
  • Osnabruck, Germany, 49078
  • Potsdam, Germany, 14480
  • Regensburg, Germany, 93053
  • Rostock, Germany, 18055
  • Tubingen, Germany, 72076
• Greece
  • Athens, Greece, 16121
  • Crete, Greece, 71201
• Italy
  • Benevento, Italy, 82100
  • Catania, Italy, 95124
  • Catanzaro, Italy, 88100
  • Coppitto-L'Aquila, Italy, 67100
  • Firenze, Italy, 50119
  • Messina, Italy, 98200
  • Milano, Italy, 20161
  • Modena, Italy, 41100
  • Padova, Italy, 35128
  • Palermo, Italy, 90127
  • Roma, Italy, 0133
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
  • Breda, Netherlands, 4818 CK
  • Maastricht, Netherlands, 6229 HX
  • Nijmegen, Netherlands, 6525 GL
  • Rotterdam, Netherlands, 3015 CA
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08025
  • Barcelona, Spain, 08916
  • Bilbao, Spain, 48903
  • Bilbao, Spain, 48013
  • Galdacano Vizcaya, Spain, 48960
  • Granada, Spain, 18012
  • Las Palmas de Gran Canarias, Spain, 35010
  • Madrid, Spain, 28006
  • Madrid, Spain, 28046
  • Madrid, Spain, 28034
  • Madrid, Spain, 28041
  • Malaga, Spain, 29071
  • Santander, Spain, 39008
  • Santiago, Spain, 15700
  • Santiago de Compostela, Spain, 15706
  • Seville, Spain, 41009
  • Valencia, Spain, 46014
  • Valencia, Spain, 46009
  • Vigo, Spain, 36024
• Sweden
  • Falun, Sweden, 79182
  • Goteborg, Sweden, 41345
  • Malmo, Sweden, 20502
  • Stockholm, Sweden, 17176
• Switzerland
  • Basel, Switzerland, 4031
  • Bern, Switzerland, 3010
  • Geneva, Switzerland, 1211
  • Zurich, Switzerland, 8091
• Turkey
  • Ankara, Turkey, 06100
  • Ankara, Turkey, 06500
  • Bursa, Turkey, 16045
  • Capa, Turkey, 34390
  • Istanbul, Turkey, 34098
  • Istanbul, Turkey, 34668
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZR
  • Cardiff, United Kingdom, CF14 4XN
  • Glasgow, United Kingdom, G11 6NT
  • Leeds, United Kingdom, LS1 3EX
  • London, United Kingdom, NW3 2QG
  • Manchester, United Kingdom, M6 8HD
  • Newport Gwent, United Kingdom, NP20 4SZ
  • Nuneaton, United Kingdom, CV10 7DJ

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Subject is >= 18 years of age
• Subject had a clinical diagnosis of chronic plaque psoriasis for at least 6 months, and has moderate to severe plaque psoriasis
• Subject must have been treated and failed to respond to, or has a contraindication to, or is intolerant to at least two different systemic therapies, one of which must be cyclosporine, or methotrexate or oral PUVA
• Subject is judged to be in generally good health as determined by the principal investigator

Exclusion Criteria:

• Subject has previous exposure to adalimumab
• Subject cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot avoid UVB or PUVA phototherapy
• Subject is taking or requires oral or injectible corticosteroids
• Subject diagnosed with erythrodermic psoriasis, pustular psoriasis, medication-induced or medication-exacerbated psoriasis or new onset guttate psoriasis
• Subject considered by the investigator, for any reason, to be an unsuitable candidate
• Female subject who is pregnant or breast-feeding or considering becoming pregnant
• Subject has a calcium metabolism disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: adalimumab + placebo; adalimumab + placebo (vehicle ointment)	Biological: adalimumab; subcutaneous injection using prefilled pen/syringe, solution containing 40 mg in 0.8 milliliters; 2 injections given at Baseline (Day 1) then once every other week from Weeks 1 though 15; Other Names: ABT-D2E7; Humira; Drug: placebo (vehicle ointment); Topical vehicle ointment (matching active calcipotriol/betamethasone ointment) to be applied once daily to affected psoriasis skin on trunk and extremities for first 4 weeks and as needed from Week 5 through Week 16
Active Comparator: adalimumab + calcipotriol/betamethasone; adalimumab + calcipotriol/betamethasone ointment	Biological: adalimumab; subcutaneous injection using prefilled pen/syringe, solution containing 40 mg in 0.8 milliliters; 2 injections given at Baseline (Day 1) then once every other week from Weeks 1 though 15; Other Names: ABT-D2E7; Humira; Drug: Calcipotriol/Betamethasone Ointment; Topical ointment (calcipotriol 50 mcg/g and betamethasone 500 mcg/g) to be applied once daily to affected psoriasis skin on trunk and extremities for first 4 weeks and as needed from Week 5 through Week 16; Other Names: Daivobet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve a PASI75 Response at Week 16 Compared With Baseline (Week 0)	PASI75 is defined as at least a 75% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement being 100%. The outcome measure is the percentage of participants who had at least a 75% PASI score decrease.	Week 0 and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a PASI50 Response at Week 16 Compared With Baseline (Week 0)	PASI50 is defined as at least a 50% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement 100%. The outcome measure is the percentage of participants who had at least a 50% PASI score decrease.	Week 0 and Week 16
Percentage of Participants With a PASI90 Response at Week 16 Compared With Baseline (Week 0)	PASI90 is defined as at least a 90% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst), with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement 100%. The outcome measure is the percentage of participants who had at least a 90% PASI score decrease.	Week 0 and Week 16
Percentage of Participants With a PASI100 Response at Week 16 Compared With Baseline (Week 0)	PASI100 is defined as at least a 100% reduction in PASI (Psoriasis Area and Severity Index) score compared with the Baseline PASI score. PASI scores range from 0.0 (best) to 72.0 (worst) with the highest score representing complete erythroderma of the severest degree. The percent decrease in score is calculated as (Week 0 PASI score minus Week 16 PASI score) divided by Week 0 PASI score. Positive percent decreases indicate improvement, with best improvement 100%. The outcome measure is the percentage of participants who had at least a 100% PASI score decrease.	Week 0 and Week 16
Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 2	PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best).	Week 2
Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 4	PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best).	Week 4
Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 8	PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best).	Week 8
Percentage of Participants Achieving a Physician's Global Assessment (PGA) of Clear or Minimal at Week 12	PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best).	Week 12
Percentage of Participants Achieving a Physicians Global Assessment (PGA) Response of Clear or Minimal at Week 16	PGA is a physician's assessment of severity of disease (grading lesion severity). PGA scores range from 0 (best) to 6 (worst): on the 6-point scale, a score of 0 = Clear and a score of 6 = Very Severe for the lesion severity. PGA Clear (0) is no plaque elevation over normal skin and no scale with or without erythema. Minimal (1) is possible plaque elevation but difficult to ascertain a slight elevation above normal skin. Percentage of participants: 0% to 100% (best).	Week 16
Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 16 Compared With Baseline (Week 0)	DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%.	Week 0 and Week 16
Percent Change in the Dermatology Life Quality Index (DLQI) Total Score at Week 2 Compared With Baseline (Week 0)	DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%.	Week 0 and Week 2
Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 4 Compared With Baseline (Week 0)	DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%.	Week 0 and Week 4
Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 8 Compared With Baseline (Week 0)	DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%.	Week 0 and Week 8
Percent Change From Baseline in the Dermatology Life Quality Index (DLQI) Total Score at Week 12 Compared With Baseline (Week 0)	DLQI is a participant-reported outcome consisting of a set of 10 questions regarding the degree to which (i.e., how much) the subject's skin has affected certain behaviors and quality of life over the last week. Responses to each are: very much, a lot, a little, or not at all. Total score range: 0 (best) to 30 (worst). Negative change and percent change from Baseline indicate improvement, with best improvement -100%.	Week 0 and Week 12
Percent Change in Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) at Week 16 Compared With Baseline (Week 0)	Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) is a participant-reported outcome that employs a questionnaire that asks for the participant's views about their health. Percent change at Week 16 is calculated as (Week 16 SF-36 PCS minus Week 0 SF-36 PCS) divided by Week 0 SF-36 PCS. Positive percent change in score indicates improvement, with best improvement 100%.	Week 0 and Week 16
Percent Change in Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) at Week 8 Compared With Baseline (Week 0)	Short Form 36 Health Survey (SF-36) Physical Component Score (PCS) is a participant-reported outcome that employs a questionnaire that asks for the participant's views about their health. Percent change at Week 8 is calculated as (Week 8 SF-36 PCS minus Week 0 SF-36 PCS) divided by Week 0 SF-36 PCS. Positive percent change in score indicates improvement, with best improvement 100%.	Week 0 and Week 8

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Psoriasis Scalp Severity Index (PSSI) From Baseline to Week 16.	PSSI is a physician assessment of clinical symptoms of scalp psoriasis. Computed as the sum of scores for erythema, induration, and desquamation (1 = absent; 4 = severest possible) multiplied by involved area (0 = 0%; 6 = 90-100%). Total score range: 0 (best) to 72 (worst). Negative change and percent change from Baseline indicate improvement.	Week 0 and Week 16
Percent Change in Nail Psoriasis Severity Index (NAPSI) at Week 16.	NAPSI is a sum of 2 scores that grade nail matrix psoriasis (based on presence/absence of pitting, leukonychia, red spots in the lunula, and nail plate crumbling) and nail bed psoriasis (based on presence/absence of onycholysis splinter hemorrhages, oil drop [salmon patch] discoloration, and nail bed hyperkeratosis). Each fingernail is given a single score based on presence of psoriasis in quadrant of nail: 0 (none) to 4 (present in 4/4 nail quadrants). Score range: 0 (best) to 80 (worst). Negative change and percent change from Baseline indicate improvement.	Week 0 and Week 16

Collaborators and Investigators

• Sponsor: Abbott

Publications and helpful links

General Publications

• Paul C, van de Kerkhof P, Puig L, Unnebrink K, Goldblum O, Thaci D. Influence of psoriatic arthritis on the efficacy of adalimumab and on the treatment response of other markers of psoriasis burden: subanalysis of the BELIEVE study. Eur J Dermatol. 2012 Nov-Dec;22(6):762-9. doi: 10.1684/ejd.2012.1863.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: December 12, 2007
• First Submitted That Met QC Criteria: December 12, 2007
• First Posted (Estimate): December 17, 2007

Study Record Updates

• Last Update Posted (Estimate): April 13, 2011
• Last Update Submitted That Met QC Criteria: April 11, 2011
• Last Verified: April 1, 2011

More Information

Terms related to this study

• Keywords: Psoriasis; Moderate Psoriasis; Chronic Plaque Psoriasis; Severe Psoriasis; Severe Chronic Plaque Psoriasis
• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dermatologic Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adalimumab; Betamethasone; Calcipotriene
• Other Study ID Numbers: M10-060