An Efficacy and Safety Study of LYC-30937-EC in Subjects With Moderate Chronic Plaque-type Psoriasis

• ClinicalTrials.gov Identifier: NCT02872285
• Recruitment Status: Completed
• First Posted: August 19, 2016
• Results First Posted: April 2, 2019
• Last Update Posted: April 10, 2019
• Sponsor: Lycera Corp.
• Information provided by (Responsible Party): Lycera Corp.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Psoriasis
• Interventions: Drug: Drug: LYC-30937-EC; Drug: Placebo
• Enrollment: 33

Participant Flow

Recruitment Details	Participants were enrolled at 7 study centers within the United States. Study centers were dermatology medical clinics experienced in conducting clinical trials.
Pre-assignment Details	Participants were 18 to 75 years of age with chronic plaque-type psoriasis for ≥ 6 months prior to screening. Eligible patients had a baseline Psoriasis Area and Severity Index (PASI) score > 7 with body surface area (BSA) involvement of 5-15% and overall lesion severity rated as moderate or marked.

Arm/Group Title	LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD
Arm/Group Description	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
Period Title: Overall Study
Started	22	11
Completed	17	9
Not Completed	5	2
Reason Not Completed
Withdrawal by Subject	2	0
Lost to Follow-up	2	2
Discontinued due to back surgery	1	0

Baseline Characteristics

Arm/Group Title		LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD	Total
Arm/Group Description		LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo	Total of all reporting groups
Overall Number of Baseline Participants		22	11	33
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	22 participants	11 participants	33 participants
		51.6 (13.91)	48.5 (12.96)	50.6 (13.48)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	11 participants	33 participants
	Female	9 40.9%	5 45.5%	14 42.4%
	Male	13 59.1%	6 54.5%	19 57.6%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	11 participants	33 participants
	Hispanic or Latino	1 4.5%	1 9.1%	2 6.1%
	Not Hispanic or Latino	21 95.5%	10 90.9%	31 93.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	22 participants	11 participants	33 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	2 9.1%	0 0.0%	2 6.1%
	White	20 90.9%	11 100.0%	31 93.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Baseline Psoriasis Area and Severity Index (PASI) score [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	22 participants	11 participants	33 participants
		9.72 (2.12)	9.38 (2.66)	9.61 (2.28)
		[1] Measure Description: The PASI is a measure of chronic plaque-type psoriasis disease. It combines lesion severity (erythema, thickness, scaling) and skin surface area involvement in 4 defined anatomical body regions (head, upper extremities, trunk, lower extremities). PASI scores range from 0 to 72 with higher scores indicative of greater disease severity. Lesion severity (erythema, thickness, scaling) is scored on a scale of 0 (none) to 4 (very severe) on each of the 4 body regions. Degree of skin area involvement in each body region is scored on a scale of 0 (no involvement) to 6 (90-100% involvement).

Outcome Measures

1. Primary Outcome

Title	The Mean Percent Change From Baseline to Week 12 in Psoriasis Area and Severity Index (PASI).
Description	This endpoint was calculated in each treatment group by taking the Week 12 PASI score and subtracting the baseline PASI and dividing by the baseline PASI, then multiplying by 100 to get the percent change from baseline. The PASI is a measure of chronic plaque-type psoriasis disease. It combines lesion severity (erythema, thickness, scaling) and skin surface area involvement in 4 defined anatomical body regions (head, upper extremities, trunk, lower extremities). PASI score ranges from 0 to 72 with higher scores indicative of greater disease severity. Lesion severity (erythema, thickness, scaling) is scored on a scale of 0 (none) to 4 (very severe) on each of the 4 body regions. Degree of skin area involvement in each body region is scored on a scale of 0 (no involvement) to 6 (90-100% involvement).
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized subjects. Randomized subjects included in this analysis had to have both a baseline and a Week 12 PASI score.

Arm/Group Title	LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD
Arm/Group Description:	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	18	9
Mean (Standard Deviation); Unit of Measure: percent change
	-25.08 (26.43)	-12.63 (19.67)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LYC-30937-EC 25 mg PO QD, Matching Placebo PO QD
	Comments	Subjects included in this analysis had to have both a baseline and Week 12 PASI scores.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.2205
	Comments	ANCOVA was used to compare mean percent change in PASI score between baseline and Week 12 between LYC-30937 and placebo treatment groups with treatment as a factor and baseline as a covariate.
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-12.80
	Confidence Interval	(2-Sided) 95%; -33.793 to 8.199
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	The Number of Subjects Who Achieve a ≥ 75% Reduction From Baseline in PASI at Week 12.
Description	This endpoint calculated the number of subjects achieving a ≥ 75% reduction in their Week 12 PASI score compared to their baseline PASI. The PASI is a measure of chronic plaque-type psoriasis disease. It combines lesion severity (erythema, thickness, scaling) and skin surface area involvement in 4 defined anatomical body regions (head, upper extremities, trunk, lower extremities). PASI score ranges from 0 to 72 with higher scores indicative of greater disease severity. Lesion severity (erythema, thickness, scaling) is scored on a scale of 0 (none) to 4 (very severe) on each of the 4 body regions. Degree of skin area involvement in each body region is scored on a scale of 0 (no involvement) to 6 (90-100% involvement).
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized subjects. Randomized subjects included in this analysis were those with PASI scores at baseline and at Week 12.

Arm/Group Title	LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD
Arm/Group Description:	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	18	9
Measure Type: Count of Participants; Unit of Measure: Participants
	1 5.6%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LYC-30937-EC 25 mg PO QD, Matching Placebo PO QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4712
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	2-sided p-value.

3. Secondary Outcome

Title	The Mean Percent Change From Baseline to Week 12 in Percent Body Surface Area (BSA).
Description	Mean percent change from baseline to Week 12 in %BSA was calculated by taking the Week 12 %BSA and subtracting the baseline %BSA then dividing by the baseline %BSA and multiplying by 100. The mean percent change from baseline to Week 12 in each treatment group were compared using analysis of covariance with treatment as a factor and baseline as a covariate.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized subjects. Randomized subjects included in this analysis had to have both a baseline and a Week 12 %BSA score.

Arm/Group Title	LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD
Arm/Group Description:	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	18	9
Mean (Standard Deviation); Unit of Measure: percent change
	-12.69 (26.18)	-7.68 (35.75)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LYC-30937-EC 25 mg PO QD, Matching Placebo PO QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.6695
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.34
	Confidence Interval	(2-Sided) 95%; -30.87 to 20.18
	Estimation Comments	[Not Specified]

4. Secondary Outcome

Title	The Number of Subjects Who Achieve "Cleared" (Score = 0) or "Minimal" (Score = 1) on the Static Investigators Global Assessment at Week 12.
Description	This endpoint is number of subjects who achieved a score of 0 or 1 on the static IGA at week 12. The static IGA is used to measure psoriasis severity. The static IGA used in this study was a 6-point scale: 0 = Cleared [no plaque elevation, erythema or scaling, hyperpigmentation may be present]; 1 = Minimal [minimal plaque elevation (=0.25mm), faint erythema, minimal scaling with occasional fine scale over < 5% of lesion]; 2 = Mild [mild plaque elevation (=0.5mm), light red coloration, fine scale predominates]; 3 = Moderate [moderate plaque elevation (=0.75mm), moderate red coloration, coarse scale predominates]; 4 = Marked (marked plaque elevation (=1mm), bright red coloration, thick non-tenacious scale predominates]; 5 = Severe (severe plaque elevation (≥1.25mm), dusky to deep red coloration, very thick tenacious scale predominates].
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized subjects. Randomized subjects included in this analysis had to have both a baseline and a Week 12 static IGA score.

Arm/Group Title	LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD
Arm/Group Description:	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	18	9
Measure Type: Count of Participants; Unit of Measure: Participants
	1 5.6%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LYC-30937-EC 25 mg PO QD, Matching Placebo PO QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4712
	Comments	2-sided p-value
	Method	Chi-squared
	Comments	[Not Specified]

5. Secondary Outcome

Title	The Number of Subjects Who Achieve a 2 Step Reduction on the Static Investigators Global Assessment (IGA) at Week 12.
Description	This endpoint is based on number of subjects who achieved a 2 step reduction in the static IGA at week 12 (ie, a score of 5 at baseline to a score of 3 or less at Week 12). The static IGA is used to measure psoriasis severity. The static IGA used in this study was a 6-point scale: 0 = Cleared [no plaque elevation, erythema or scaling, hyperpigmentation may be present]; 1 = Minimal [minimal plaque elevation (=0.25mm), faint erythema, minimal scaling with occasional fine scale over < 5% of lesion]; 2 = Mild [mild plaque elevation (=0.5mm), light red coloration, fine scale predominates]; 3 = Moderate [moderate plaque elevation (=0.75mm), moderate red coloration, coarse scale predominates]; 4 = Marked (marked plaque elevation (=1mm), bright red coloration, thick non-tenacious scale predominates]; 5 = Severe (severe plaque elevation (≥1.25mm), dusky to deep red coloration, very thick tenacious scale predominates].
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The full analysis set included all randomized subjects. Randomized subjects included in this analysis had to have both a baseline and a Week 12 static IGA score.

Arm/Group Title	LYC-30937-EC 25 mg PO QD	Matching Placebo PO QD
Arm/Group Description:	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC	Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
Overall Number of Participants Analyzed	18	9
Measure Type: Count of Participants; Unit of Measure: Participants
	1 5.6%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LYC-30937-EC 25 mg PO QD, Matching Placebo PO QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.4712
	Comments	2-sided p-value
	Method	Chi-squared
	Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events were collected from the time subjects signed the study informed consent until the Week 14 follow-up visit. Treatment-emergent adverse events were those adverse events occurring or worsening after the first dose of study drug (LYC-30937-EC or placebo) up to the Week 14 follow-up visit.
Adverse Event Reporting Description	AE severity was assessed by the Investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v 4.03, with grading as follows: Grade 1 = mild (asymptomatic or mild symptoms), Grade 2 = moderate (minimal, local intervention, or noninvasive intervention indicated); Grade 3 = severe (or medically significant but not life-threatening); Grade 4 = life-threatening; Grade 5 = death.
Arm/Group Title	LYC-30937-EC 25 mg PO QD		Matching Placebo PO QD
Arm/Group Description	LYC-30937-EC 25 mg by mouth once daily for 12 weeks Drug: LYC-30937-EC		Placebo enteric coated (EC) by mouth once daily for 12 weeks Placebo
All-Cause Mortality
	LYC-30937-EC 25 mg PO QD		Matching Placebo PO QD
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/22 (0.00%)		0/11 (0.00%)
Serious Adverse Events
	LYC-30937-EC 25 mg PO QD		Matching Placebo PO QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0.00%)		0/11 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	LYC-30937-EC 25 mg PO QD		Matching Placebo PO QD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/22 (50.00%)		4/11 (36.36%)
Blood and lymphatic system disorders
Lymphadenopathy † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
Gastrointestinal disorders
Diarrhoea † 1	1/22 (4.55%)	2	1/11 (9.09%)	2
Flatulence † 1	0/22 (0.00%)	0	2/11 (18.18%)	2
General disorders
Fatigue † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
Infections and infestations
Gastroenteritis viral † 1	2/22 (9.09%)	2	0/11 (0.00%)	0
Nasopharyngitis † 1	2/22 (9.09%)	2	0/11 (0.00%)	0
Upper respiratory tract infection † 1	2/22 (9.09%)	2	0/11 (0.00%)	0
Injury, poisoning and procedural complications
Fractured coccyx † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/22 (0.00%)	0	1/11 (9.09%)	2
Nervous system disorders
Headache † 1	2/22 (9.09%)	6	0/11 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough † 1	2/22 (9.09%)	2	0/11 (0.00%)	0
Oropharyngeal pain † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
Skin and subcutaneous tissue disorders
Pruritis † 1	2/22 (9.09%)	2	0/11 (0.00%)	0
Psoriasis † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
Seborroea † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
Vascular disorders
Varicose vein † 1	0/22 (0.00%)	0	1/11 (9.09%)	1
1 Term from vocabulary, MedDRA (19.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

Center results cannot be submitted for publication before results of multicenter study are published unless it is ≥18 months since study completion. Then Investigator can publish if manuscript is submitted to Lycera ≥ 60 days prior to submission (or per Investigator contract). If Lycera decides publication would hinder development, Investigator must delay submission. Investigator must delete confidential information before submission and defer publication to allow patent applications.

Results Point of Contact

• Name/Title: H. Jeffrey Wilkins MD, Chief Medical Officer
• Organization: Lycera Corp.
• Phone: 484-243-6222
• EMail: wilkins@lycera.com

• Responsible Party: Lycera Corp.
• ClinicalTrials.gov Identifier: NCT02872285
• Other Study ID Numbers: LYC-30937-2003
• First Submitted: August 16, 2016
• First Posted: August 19, 2016
• Results First Submitted: January 29, 2019
• Results First Posted: April 2, 2019
• Last Update Posted: April 10, 2019