Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

LEO 90100 Twice Weekly Maintenance Regimen for Psoriasis Vulgaris

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02899962
Recruitment Status : Completed
First Posted : September 14, 2016
Results First Posted : August 20, 2020
Last Update Posted : August 20, 2020
Sponsor:
Information provided by (Responsible Party):
LEO Pharma

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Psoriasis Vulgaris
Interventions Drug: LEO 90100 aerosol foam
Drug: LEO 90100 aerosol foam vehicle
Enrollment 722
Recruitment Details  
Pre-assignment Details 722 subjects were screened of which 650 subjects were assigned to treatment with LEO 90100 open-label phase. Subjects did not progress from screening due to adverse event=1, lost to follow-up=2, other reasons=2, screening failures=52, and withdrawal by subject=15. All 650 subjects were exposed to LEO 90100 during the open-label phase
Arm/Group Title Open-label LEO 90100 Maintenance LEO 90100 Maintenance Vehicle
Hide Arm/Group Description In the open-label phase, LEO 90100, an aerosol foam formulation containing calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) was applied once daily on the body for 4 weeks. In the maintenance phase, subjects from open-label phase who achieved treatment success according to Physician's Global Assessment of disease severity (clear or almost clear with 2-step improvement) were randomised to receive LEO 90100 twice weekly for 52 weeks. In case of relapse (psoriasis which was mild, moderate or severe according to PGA), rescue medication was applied. Rescue medication was LEO 90100 applied once daily on the body for 4 weeks. In the maintenance phase, subjects from open-label phase who achieved treatment success according to Physician's Global Assessment of disease severity (clear or almost clear with 2-step improvement) were randomised to receive vehicle twice weekly for 52 weeks. In case of relapse (psoriasis which was mild, moderate or severe according to PGA), rescue medication was applied. Rescue medication was LEO 90100 applied once daily on the body for 4 weeks.
Period Title: Open-label Phase
Started 650 0 0
Completed 623 0 0
Not Completed 27 0 0
Reason Not Completed
Adverse Event             2             0             0
Lost to Follow-up             9             0             0
Other reasons             9             0             0
Withdrawal by Subject             7             0             0
Period Title: Maintenance Phase
Started 0 272 273
Completed 0 131 120
Not Completed 0 141 153
Reason Not Completed
Adverse Event             0             2             1
Death             0             0             1
Lack of Efficacy             0             20             16
Lost to Follow-up             0             12             14
Other reasons             0             9             13
Not achieve treatment success after Wk 4             0             3             2
Not clear/almost clear after rescue med             0             65             70
Withdrawal by Subject             0             30             36
Arm/Group Title LEO 90100 Open-label Phase
Hide Arm/Group Description LEO 90100, an aerosol foam formulation containing calcipotriol 50 mcg/g (as hydrate) and betamethasone 0.5 mg/g (as dipropionate) was applied once daily on the body for 4 weeks.
Overall Number of Baseline Participants 650
Hide Baseline Analysis Population Description
Included all subjects exposed to LEO 90100 at the start of open-label phase
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 650 participants
51.8  (14.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 650 participants
Female
226
  34.8%
Male
424
  65.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 650 participants
Hispanic or Latino
75
  11.5%
Not Hispanic or Latino
568
  87.4%
Unknown or Not Reported
7
   1.1%
Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 635 participants
White
584
  92.0%
Asian
37
   5.8%
Black or African American
9
   1.4%
Native Hawaiian or Other Pacific Islander
4
   0.6%
American Indian or Alaska Native
1
   0.2%
[1]
Measure Analysis Population Description: Data available only from 635 subjects
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Canada Number Analyzed 650 participants
163
United States Number Analyzed 650 participants
228
Poland Number Analyzed 650 participants
60
United Kingdom Number Analyzed 650 participants
79
France Number Analyzed 650 participants
61
Germany Number Analyzed 650 participants
59
PGA   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 650 participants
Mild
83
  12.8%
Moderate
509
  78.3%
Severe
58
   8.9%
[1]
Measure Description:

The investigator was to grade the severity of psoriasis of the trunk and limbs using the 5-point scale Physician's global assessment of the disease severity:

Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4

1.Primary Outcome
Title Time to First Relapse
Hide Description Time to first relapse (at least 'mild' according to the Physician's Global Assessment of disease severity [PGA]). The investigator was to grade the severity of psoriasis of the trunk and limbs using Physician's global assessment of disease severity 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4
Time Frame From Randomisation (Week 4) until first relapse or End of Treatment (Week 56 or early withdrawal)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set: included all subjects randomised who had treatment success at randomisation, defined as PGA score of 'clear' or 'almost clear' with at least a 2-grade improvement from baseline
Arm/Group Title LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Hide Arm/Group Description:
Topical application of LEO 90100 aerosol foam twice weekly for 52 weeks
Topical application of LEO 90100 aerosol foam vehicle twice weekly for 52 weeks
Overall Number of Participants Analyzed 256 265
Median (95% Confidence Interval)
Unit of Measure: days
56
(34 to 59)
30
(29 to 31)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LEO 90100 Aerosol Foam, LEO 90100 Aerosol Foam Vehicle
Comments All randomized subjects were considered for statistical analysis.
Type of Statistical Test Superiority
Comments The primary endpoint was time to first relapse during the maintenance phase. This was calculated as the number of days from randomisation to the day where the subject had the first relapse confirmed. For subjects who either did not encounter a relapse or were withdrawn from the trial, the number of days was treated as a censored observation at the day of end of trial visit.
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.47 to 0.69
Estimation Comments Estimates are obtained from a proportional hazards model with treatment group,pooled trial site,disease severity at maintenance baseline (Week 4; determined by PGA) as factors.
2.Secondary Outcome
Title Proportion of Days in Remission During the Maintenance Phase
Hide Description Remission defined as 'clear' or 'almost clear' according to the PGA. The investigator was to grade using a global assessment of the disease severity of psoriasis of the trunk and limbs using the PGA 5-point scale: Clear = 0; Almost clear = 1; Mild = 2; Moderate = 3; Severe = 4
Time Frame From Randomisation (Week 4) until End of Treatment (Week 56 or early withdrawal)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Hide Arm/Group Description:
Topical application of LEO 90100 aerosol foam twice weekly for 52 weeks
Topical application of LEO 90100 aerosol foam vehicle twice weekly for 52 weeks
Overall Number of Participants Analyzed 256 265
Mean (Standard Deviation)
Unit of Measure: Proportion of days
70.2  (21.7) 60.8  (20.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LEO 90100 Aerosol Foam, LEO 90100 Aerosol Foam Vehicle
Comments The number of days in remission was calculated as the sum of days where the subject was in remission periods. The proportion of days in remission was calculated as the number of days in remission divided by the length of the maintenance phase in days.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANOVA
Comments Factors adjusted for in the ANOVA model were treatment group, pooled trial site, and disease severity at maintenance baseline (PGA).
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.08 to 0.14
Estimation Comments Multiple imputation of data for withdrawn subjects was done using 100 imputations and depended on whether the subject's reason for withdrawal potentially was related to treatment. Length of the maintenance phase was assumed to be 52 weeks (364 days)
3.Secondary Outcome
Title Number of Relapses During the Maintenance Phase
Hide Description Defined as number of 4-week periods with use of once-daily rescue investigational medicinal product
Time Frame From Randomisation (Week 4) until End of Treatment (Week 56)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Hide Arm/Group Description:
Topical application of LEO 90100 aerosol foam twice weekly for 52 weeks
Topical application of LEO 90100 aerosol foam vehicle twice weekly for 52 weeks
Overall Number of Participants Analyzed 256 265
Mean (Standard Deviation)
Unit of Measure: relapses
2.0  (1.7) 3.1  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection LEO 90100 Aerosol Foam, LEO 90100 Aerosol Foam Vehicle
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Poisson regression
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.54
Confidence Interval (2-Sided) 95%
0.46 to 0.63
Estimation Comments The number of relapses was analysed using a Poisson regression model with treatment group,pooled sites,disease severity at maintenance baseline as factors, subject as random effect, and time at risk as an offset.
Time Frame 4 weeks during the open-label phase and 52 weeks during the maintenance phase and 8 weeks during the safety follow-up
Adverse Event Reporting Description All adverse events were reported by the subjects or observed by the investigators were recorded
 
Arm/Group Title LEO 90100 Aerosol Foam Open-label LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Hide Arm/Group Description

Topical application once daily for 4 weeks

LEO 90100 aerosol foam open-label

Topical application twice weekly for 52 weeks

LEO 90100 aerosol foam: LEO 90100 aerosol foam twice weekly

Topical application twice weekly for 52 weeks

LEO 90100 aerosol foam vehicle: LEO 90100 aerosol foam vehicle twice weekly

All-Cause Mortality
LEO 90100 Aerosol Foam Open-label LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/650 (0.00%)      0/272 (0.00%)      1/273 (0.37%)    
Hide Serious Adverse Events
LEO 90100 Aerosol Foam Open-label LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/650 (0.62%)      14/272 (5.15%)      11/273 (4.03%)    
Cardiac disorders       
Myocardial ischaemia * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Coronary artery occlusion * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Acute myocardial infarction * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Atrial fibrillation * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Mitral valve incompetence * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Ear and labyrinth disorders       
Vertigo * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Gastrointestinal disorders       
Alcoholic pancreatitis * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Small intestinal obstruction * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Colitis * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
General disorders       
Chest pain * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Immune system disorders       
Drug hypersensitivity * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Infections and infestations       
Pneumonia * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Atypical pneumonia * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Appendicitis * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Endocarditis * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Injury, poisoning and procedural complications       
Intentional overdose * 1  1/650 (0.15%)  2 0/272 (0.00%)  0 1/273 (0.37%)  4
Gun shot wound * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Metabolism and nutrition disorders       
Electrolyte imbalance * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Myositis * 1  1/650 (0.15%)  1 0/272 (0.00%)  0 0/273 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Prostate cancer * 1  1/650 (0.15%)  1 1/272 (0.37%)  1 0/273 (0.00%)  0
Nervous system disorders       
Cerebrovascular accident * 1  1/650 (0.15%)  1 1/272 (0.37%)  1 0/273 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Pneumothorax * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Pulmonary embolism * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
Vascular disorders       
Arterial stenosis * 1  0/650 (0.00%)  0 2/272 (0.74%)  2 0/273 (0.00%)  0
Hypertension * 1  0/650 (0.00%)  0 1/272 (0.37%)  1 0/273 (0.00%)  0
Venous thrombosis * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 1/273 (0.37%)  1
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
LEO 90100 Aerosol Foam Open-label LEO 90100 Aerosol Foam LEO 90100 Aerosol Foam Vehicle
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   47/650 (7.23%)      83/272 (30.51%)      87/273 (31.87%)    
Eye disorders       
Cataract * 1  0/650 (0.00%)  0 3/272 (1.10%)  4 0/273 (0.00%)  0
Gastrointestinal disorders       
Diarrhoea * 1  2/650 (0.31%)  2 1/272 (0.37%)  1 3/273 (1.10%)  3
General disorders       
Chest pain * 1  1/650 (0.15%)  1 3/272 (1.10%)  3 0/273 (0.00%)  0
Infections and infestations       
Upper respiratory tract infection * 1  7/650 (1.08%)  7 16/272 (5.88%)  17 15/273 (5.49%)  24
Nasopharyngitis * 1  7/650 (1.08%)  7 22/272 (8.09%)  23 19/273 (6.96%)  24
Influenza * 1  2/650 (0.31%)  2 7/272 (2.57%)  7 3/273 (1.10%)  3
Urinary tract infection * 1  2/650 (0.31%)  2 3/272 (1.10%)  3 6/273 (2.20%)  6
Bronchitis * 1  1/650 (0.15%)  1 2/272 (0.74%)  2 5/273 (1.83%)  5
Sinusitis * 1  2/650 (0.31%)  2 5/272 (1.84%)  5 2/273 (0.73%)  3
Gastroenteritis * 1  3/650 (0.46%)  3 4/272 (1.47%)  4 2/273 (0.73%)  2
Folliculitis * 1  2/650 (0.31%)  2 4/272 (1.47%)  4 2/273 (0.73%)  2
Lower respiratory tract infection * 1  0/650 (0.00%)  0 3/272 (1.10%)  3 3/273 (1.10%)  3
Injury, poisoning and procedural complications       
Fall * 1  0/650 (0.00%)  0 5/272 (1.84%)  5 0/273 (0.00%)  0
Ligament sprain * 1  1/650 (0.15%)  1 1/272 (0.37%)  2 4/273 (1.47%)  4
Joint injury * 1  0/650 (0.00%)  0 3/272 (1.10%)  3 0/273 (0.00%)  0
Laceration * 1  1/650 (0.15%)  1 2/272 (0.74%)  2 3/273 (1.10%)  3
Contusion * 1  1/650 (0.15%)  1 2/272 (0.74%)  2 3/273 (1.10%)  3
Metabolism and nutrition disorders       
Vitamin D deficiency * 1  36/650 (5.54%)  36 1/272 (0.37%)  1 2/273 (0.73%)  2
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  3/650 (0.46%)  4 4/272 (1.47%)  4 6/273 (2.20%)  6
Back pain * 1  4/650 (0.62%)  4 6/272 (2.21%)  7 4/273 (1.47%)  4
Pain in extremity * 1  3/650 (0.46%)  3 4/272 (1.47%)  4 2/273 (0.73%)  2
Nervous system disorders       
Sciatica * 1  0/650 (0.00%)  0 4/272 (1.47%)  4 3/273 (1.10%)  3
Dizziness * 1  1/650 (0.15%)  1 3/272 (1.10%)  4 0/273 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Chronic obstructive pulmonary disease * 1  0/650 (0.00%)  0 0/272 (0.00%)  0 3/273 (1.10%)  3
Skin and subcutaneous tissue disorders       
Rebound psoriasis * 1  0/650 (0.00%)  0 4/272 (1.47%)  4 12/273 (4.40%)  12
Psoriasis * 1  3/650 (0.46%)  3 1/272 (0.37%)  1 7/273 (2.56%)  7
Actinic keratosis * 1  0/650 (0.00%)  0 3/272 (1.10%)  3 0/273 (0.00%)  0
Vascular disorders       
Hypertension * 1  6/650 (0.92%)  6 4/272 (1.47%)  4 3/273 (1.10%)  3
1
Term from vocabulary, MedDRA (19.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
LEO Pharma acknowledges the investigators' right to publish the entire results of the study, irrespective of outcome. LEO Pharma retains the right to have any publication submitted to LEO Pharma for review. Investigators must undertake not to submit any part of their individual data for publication without the prior consent of LEO Pharma.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Disclosure Specialist
Organization: LEO Pharma A/S
Phone: +45 44945888
EMail: disclosure@leo-pharma.com
Layout table for additonal information
Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT02899962    
Other Study ID Numbers: LP0053-1004
First Submitted: September 9, 2016
First Posted: September 14, 2016
Results First Submitted: July 10, 2020
Results First Posted: August 20, 2020
Last Update Posted: August 20, 2020