Efficacy and Safety of LEO 90100 Foam in Japanese Subjects With Psoriasis Vulgaris

• Sponsor: LEO Pharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03806790
• Collaborator: (none)
• Enrollment: 182
• Locations: 16
• Arms: 2
• Actual Duration (Months): 4.5
• Patients Per Site: 11.4
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

Comparison of the efficacy of LEO 90100 foam with Dovobet® ointment in the treatment of psoriasis in Japanese subjects.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis Vulgaris	Drug: LEO 90100 foam; Drug: Dovobet® ointment	Phase 3

Detailed Description

A phase 3, national, multi-centre, 4-week, prospective, randomised, controlled, parallel-group, open trial of LEO 90100 foam versus Dovobet® ointment (both treatments containing calcipotriol hydrate plus betamethasone dipropionate) in Japanese subjects with psoriasis vulgaris.

Study Design

• Study Type: Interventional
• Actual Enrollment: 182 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of LEO 90100 Foam in Japanese Subjects With Psoriasis Vulgaris
• Actual Study Start Date: Jan 24, 2019
• Actual Primary Completion Date: Jun 10, 2019
• Actual Study Completion Date: Jun 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LEO 90100 foam calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g	Drug: LEO 90100 foam; Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.; Other Names: Enstilar® Foam
Active Comparator: Dovobet® ointment calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g	Drug: Dovobet® ointment; Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.

Outcome Measures

Primary Outcome Measures

1. Overall Improvement Rate for the Target Lesion [End of Week 4]

   Overall improvement defined as 'Substantial Resolution' of Clinical Signs or at Least 'Moderately Improved' in the General Change in the Lesion. Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the target lesion. The details of the clinical scores are presented in secondary outcome measure description for 'Change in the total sign score'. Change in the Lesion is a 5 point scale below: Markedly improved (best outcome) Moderately improved Slightly improved Unchanged Aggravated (worst outcome)

Secondary Outcome Measures

1. Overall Improvement Rate for the Target Lesion at Weeks 1 and 2 [End of Weeks 1 and 2]

   Substantial resolution of clinical signs or at least 'moderately improved' in the general change in the target lesion. Change in the Lesion is a 5 point scale below: Markedly improved (best outcome) Moderately improved Slightly improved Unchanged Aggravated (worst outcome)

2. Change in the Total Sign Score for the Target Lesion From Week 0 to Week 4 [End of Week 4]

   The change in the total sign score from Week 0 to Week 4; total sign score is defined as the sum of the scores from the 3 clinical signs (redness, thickness, and scaliness) assessing severity in the target lesion. The severity for each of the 3 clinical signs was recorded according to a 9-point scale that ranges from a score of 0 to 4 in increments of 0.5; the severities are scored from low to high with 0 = none and 4 = severe. The sum of the 3 total sign scores could range from 0 (best) to 12 (worse). The greater the negative value for the change means a better outcome. Negative change denotes a decrease in the score and therefore a decrease in disease severity.

3. Number of Adverse Events [Treatment Emergent Adverse Events were assessed from Day 1 to end of Week 4, if Treatment Emergent Adverse Events were noted, they were followed for an additional 14 days]

   Number of treatment emergent adverse events (TEAEs). 14-day follow-up of TEAEs was only required if the TEAE was present at the last visit, and was of possible or probable relationship to trial medication.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Signed and dated informed consent obtained

2. Japanese subjects

3. Aged 20 years or above

4. Clinical diagnosis of psoriasis vulgaris amenable to topical treatment of less than or equal to 30% BSA (excluding psoriasis on the face/genitals/skin folds).

5. A target psoriasis lesion of at least mild severity on the body of a minimum size of 10 cm2 and scoring at least 2 (mild) for each of the clinical signs). The lesion must not be on the scalp, face, genitals or skin folds.

6. Women of childbearing potential must have a negative pregnancy test at Day 1 and agree to use an adequate methods of birth control during the trial.

7. Able to communicate with the (sub)investigator and understand and comply with the requirements of the trial.

Key Exclusion Criteria:

1. Systemic use of biological treatments with a potential effect on psoriasis vulgaris within the specified time periods prior to randomisation (depending on treatment)

2. Systemic treatments with all therapies other than biological treatments with a potential effect on psoriasis vulgaris within 4 weeks prior to randomisation

3. PUVA therapy, UVB therapy or UVA therapy on the full body or on the target lesion within 4 weeks prior to randomisation

4. Topical treatment of psoriasis on the areas to be treated with trial medication within 2 weeks prior to randomisation

5. Topical treatment of psoriasis on the face, genitals or skin folds with vitamin D3 analogues, potent corticosteroids or immunosuppressants within 2 weeks prior to randomisation

6. Topical treatment of conditions other than psoriasis with vitamin D3 analogues, potent corticosteroids or immunosuppressants within 2 weeks prior to randomisation

7. Initiation or changes of medication that may affect psoriasis vulgaris during the trial

8. Patients with certain disorders or symptoms present on the areas to be treated with trial medication: viral lesions of the skin, infections, skin manifestations, or fragility of skin veins

9. Other inflammatory skin diseases that may confound the evaluation of psoriasis vulgaris

10. Erythrodermic, exfoliative or pustular psoriasis on the areas to be treated with trial medication

11. Planned excessive exposure of areas to be treated with trial medication to either natural or artificial sunlight during the trial.

12. Disorders of calcium metabolism

13. Severe renal insufficiency, severe hepatic disorders or severe heart disease

14. Hypersensitivity to any components of the investigational medicinal products.

15. Cushing's disease or Addison's disease

16. Subjects who have received treatment with any non-marketed drug substance within the 4 weeks prior to randomisation, or longer if for certain biological treatments

17. History of cancer within the last 5 years (except completely cured skin cancer)

18. Current participation in any other interventional clinical trial

19. Previously randomised in this trial

20. Women who are pregnant, wishing to become pregnant or are breast-feeding

21. Chronic alcohol or drug abuse within 12 months prior to screening, or any condition associated with poor compliance

22. Employees of the trial site or any other individuals directly involved with the planning or conduct of the trial, or immediate family members of such individuals

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Leo Pharma Investigational Site	Fukutsu	Fukuoka	Japan	811-3217
2	Leo Pharma Investigational Site	Obihiro	Hokkaido	Japan	080-0013
3	Leo Pharma Investigational Site	Sapporo	Hokkaido	Japan	004-0063
4	Leo Pharma Investigational Site	Sapporo	Hokkaido	Japan	006-0814
5	Leo Pharma Investigational Site	Sapporo	Hokkaido	Japan	060-0807
6	Leo Pharma Investigational Site	Nonoichi	Ishikawa	Japan	921-8801
7	Leo Pharma Investigational Site	Kawasaki	Kanagawa	Japan	213-0001
8	Leo Pharma Investigational Site	Yokohama	Kanagawa	Japan	220-6208
9	Leo Pharma Investigational Site	Sendai	Miyagi	Japan	981-3133
10	Leo Pharma Investigational Site	Saitama-shi	Saitama	Japan	330-0854
11	Leo Pharma Investigational Site	Itabashi-ku	Tokyo	Japan	173-8605
12	Leo Pharma Investigational Site	Kita-ku	Tokyo	Japan	115-0045
13	Leo Pharma Investigational Site	Koto-Ku	Tokyo	Japan	136-0074
14	Leo Pharma Investigational Site	Minato-Ku	Tokyo	Japan	108-0014
15	Leo Pharma Investigational Site	Setagaya	Tokyo	Japan	158-0094
16	Leo Pharma Investigational Site	Setagaya	Tokyo	Japan	158-0097

Sponsors and Collaborators

• LEO Pharma

Investigators

• Study Director: Medical Expert, LEO Pharma

Study Documents (Full-Text)

• Study Protocol - Nov 6, 2018
• Statistical Analysis Plan - Jun 21, 2019

More Information

Publications

None provided.

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT03806790
• Other Study ID Numbers: LP0053-1422
• First Posted: Jan 16, 2019
• Last Update Posted: Dec 16, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Arm/Group Title	LEO 90100 Foam	Dovobet® Ointment
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
Period Title: Overall Study
STARTED	87	95
COMPLETED	87	95
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	LEO 90100 Foam	Dovobet® Ointment	Total
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.	Total of all reporting groups
Overall Participants	87	95	182
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.2 (13.6)	54.8 (12.9)	54.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	29 33.3%	34 35.8%	63 34.6%
Male	58 66.7%	61 64.2%	119 65.4%
Race/Ethnicity, Customized (Count of Participants)
Japanese	87 100%	95 100%	182 100%
Region of Enrollment (participants) [Number]
Japan	87 100%	95 100%	182 100%

Outcome Measures

1. Primary Outcome

Title	Overall Improvement Rate for the Target Lesion
Description	Overall improvement defined as 'Substantial Resolution' of Clinical Signs or at Least 'Moderately Improved' in the General Change in the Lesion. Substantial resolution' is defined as a clinical score for thickness and scaliness of 0 and a clinical score for redness of 1 or less in the severity of clinical signs of the target lesion. The details of the clinical scores are presented in secondary outcome measure description for 'Change in the total sign score'. Change in the Lesion is a 5 point scale below: Markedly improved (best outcome) Moderately improved Slightly improved Unchanged Aggravated (worst outcome)
Time Frame	End of Week 4

Outcome Measure Data

Analysis Population Description

The primary endpoint was analysed for the full analysis set. Rates of subjects with the event defined by the primary endpoint, 'overall improvement rate' for the target lesion at Visit 4 (end of Week 4), were compared between treatment groups by means of Fisher's exact test. Estimated rates, odds ratio, and its 95% CI were presented, together with the p-value from Fisher's exact test.

Arm/Group Title	LEO 90100 Foam	Dovobet® Ointment
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
Measure Participants	87	95
Count of Participants [Participants]	86 98.9%	89 93.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LEO 90100 Foam, Dovobet® Ointment
	Comments	Statistical analysis on the Full Analysis Set (FAS)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.120
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.80
	Confidence Interval	(2-Sided) 95%; 0.68 to 49.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Overall Improvement Rate for the Target Lesion at Weeks 1 and 2
Description	Substantial resolution of clinical signs or at least 'moderately improved' in the general change in the target lesion. Change in the Lesion is a 5 point scale below: Markedly improved (best outcome) Moderately improved Slightly improved Unchanged Aggravated (worst outcome)
Time Frame	End of Weeks 1 and 2

Outcome Measure Data

Analysis Population Description

The secondary endpoints were analysed for the full analysis set. The number and percentage of subjects with 'overall improvement' were tabulated for Visits 2 and 3 (end of Weeks 1 and 2) and by treatment group.

Arm/Group Title	LEO 90100 Foam	Dovobet® Ointment
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
Measure Participants	87	95
Week 1	61 70.1%	46 48.4%
Week 2	83 95.4%	77 81.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LEO 90100 Foam, Dovobet® Ointment
	Comments	End of Week 1 (FAS)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.50
	Confidence Interval	(2-Sided) 95%; 1.36 to 4.60
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LEO 90100 Foam, Dovobet® Ointment
	Comments	End of Week 2 (FAS)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.85
	Confidence Interval	(2-Sided) 95%; 1.57 to 14.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in the Total Sign Score for the Target Lesion From Week 0 to Week 4
Description	The change in the total sign score from Week 0 to Week 4; total sign score is defined as the sum of the scores from the 3 clinical signs (redness, thickness, and scaliness) assessing severity in the target lesion. The severity for each of the 3 clinical signs was recorded according to a 9-point scale that ranges from a score of 0 to 4 in increments of 0.5; the severities are scored from low to high with 0 = none and 4 = severe. The sum of the 3 total sign scores could range from 0 (best) to 12 (worse). The greater the negative value for the change means a better outcome. Negative change denotes a decrease in the score and therefore a decrease in disease severity.
Time Frame	End of Week 4

Outcome Measure Data

Analysis Population Description

The secondary endpoints were analysed for the full analysis set. For the change in the total sign score, the estimated difference between the treatment groups in the mean change (LEO 90100 foam group - Dovobet® ointment group) was calculated with 95% confidence interval. The treatment difference of the change in the total sign score at Visit 4 was estimated with an ANOVA with treatment as fixed effect.

Arm/Group Title	LEO 90100 Foam	Dovobet® Ointment
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
Measure Participants	87	95
Mean (Standard Deviation) [score on a scale]	-7.09 (1.48)	-5.98 (2.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LEO 90100 Foam, Dovobet® Ointment
	Comments	FAS
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Estimated difference
	Estimated Value	-1.11
	Confidence Interval	(2-Sided) 95%; -1.64 to -0.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Adverse Events
Description	Number of treatment emergent adverse events (TEAEs). 14-day follow-up of TEAEs was only required if the TEAE was present at the last visit, and was of possible or probable relationship to trial medication.
Time Frame	Treatment Emergent Adverse Events were assessed from Day 1 to end of Week 4, if Treatment Emergent Adverse Events were noted, they were followed for an additional 14 days

Outcome Measure Data

Analysis Population Description

The analysis of adverse events was based on the safety analysis set.

Arm/Group Title	LEO 90100 Foam	Dovobet® Ointment
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
Measure Participants	87	95
Number [participants]	15 17.2%	19 20%

Adverse Events

Time Frame	Adverse event data were collected during 4 week treatment period and up to 2 weeks after the treatment period
Arm/Group Title	LEO 90100 Foam		Dovobet® Ointment
Arm/Group Description	calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g LEO 90100 foam: Once daily topical application of foam from a can to psoriasis lesions. Dose depends on size of lesion.		calcipotriol hydrate 52.2 µg/g [equivalent to 50.0 µg/g calcipotriol] plus betamethasone dipropionate 0.643 mg/g Dovobet® ointment: Once daily topical application of ointment from a tube to psoriasis lesions. Dose depends on size of lesion.
All Cause Mortality
	LEO 90100 Foam		Dovobet® Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		0/95 (0%)
Serious Adverse Events
	LEO 90100 Foam		Dovobet® Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		0/95 (0%)
Other (Not Including Serious) Adverse Events
	LEO 90100 Foam		Dovobet® Ointment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/87 (17.2%)		19/95 (20%)
Eye disorders
Keratitis	1/87 (1.1%)	1	0/95 (0%)	1
General disorders
Pyrexia	1/87 (1.1%)	1	0/95 (0%)	1
Infections and infestations
Bronchitis	0/87 (0%)		1/95 (1.1%)	1
Folliculitis	1/87 (1.1%)	1	0/95 (0%)	1
Furuncle	0/87 (0%)		1/95 (1.1%)	1
Gingivitis	1/87 (1.1%)	1	0/95 (0%)	1
Nasopharyngitis	5/87 (5.7%)	5	5/95 (5.3%)	5
Pharyngitis	1/87 (1.1%)	1	0/95 (0%)	1
Injury, poisoning and procedural complications
Animal bite	0/87 (0%)		1/95 (1.1%)	1
Skin abrasion	0/87 (0%)		1/95 (1.1%)	1
Wound	0/87 (0%)		1/95 (1.1%)	1
Investigations
Blood calcium increased	1/87 (1.1%)	1	0/95 (0%)	1
Glycosylated haemoglobin increased	0/87 (0%)		1/95 (1.1%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/87 (0%)		1/95 (1.1%)	1
Arthritis	1/87 (1.1%)	1	0/95 (0%)	1
Tendonitis	1/87 (1.1%)	1	0/95 (0%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis	1/87 (1.1%)	1	0/95 (0%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	0/87 (0%)		1/95 (1.1%)	1
Skin and subcutaneous tissue disorders
Acne	0/87 (0%)		3/95 (3.2%)	3
Dermatitis contact	1/87 (1.1%)	1	0/95 (0%)	1
Pain of skin	1/87 (1.1%)	1	0/95 (0%)	1
Psoriasis	0/87 (0%)		1/95 (1.1%)	1
Urticaria	0/87 (0%)		1/95 (1.1%)	1
Vascular disorders
Hypertension	0/87 (0%)		1/95 (1.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

LEO Pharma A/S seeks publication of all phase 3 clinical trials in peer-reviewed journals within 18 months after completion or termination of the clinical trial, regardless of whether the findings are positive or negative. If no publication is submitted by LEO Pharma A/S within these 18 months, the investigator has the right to publish the results from the clinical trial generated by him/herself.