Trial Outcomes & Findings for An Efficacy and Safety Study of LYC-30937-EC in Subjects With Active Ulcerative Colitis (NCT NCT02762500)

Last Updated: 2019-04-02

Results Overview

The modified Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 9 points and consists of 3 subscores (stool frequency, rectal bleeding, endoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical remission on the modified Mayo score was defined as a Mayo stool frequency subscore of ≤ 1, Mayo rectal bleeding subscore of 0 and a Mayo endoscopy subscore of ≤ 1.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

8 weeks

Results posted on

2019-04-02

Participant Flow

Participants were enrolled at 42 study centers within the United States, Poland, Hungary, Czech Republic, Serbia and Netherlands. Study centers included academic medical centers and non-academic medical clinics.

Participants were 18 to 75 years of age with active ulcerative colitis for at least 6 months prior to screening, had a total Mayo score (TMS) ≥ 4 to ≤ 11, with endoscopic subscore ≥ 2, and rectal bleeding subscore ≥ 1 at screening.

Participant milestones

Participant milestones
Measure	LYC-30937-EC LYC-30937-EC 25 mg by mouth once daily for 8 weeks	Placebo Matching placebo by mouth once daily for 8 weeks
Overall Study STARTED	62	62
Overall Study COMPLETED	60	59
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	LYC-30937-EC LYC-30937-EC 25 mg by mouth once daily for 8 weeks	Placebo Matching placebo by mouth once daily for 8 weeks
Overall Study Lack of Efficacy	1	0
Overall Study Withdrawal by Subject	1	1
Overall Study Adverse Event	0	2

Baseline Characteristics

One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LYC-30937-EC n=62 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks	Placebo n=62 Participants Matching placebo by mouth once daily for 8 weeks	Total n=124 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 11.94 • n=62 Participants	39.3 years STANDARD_DEVIATION 13.26 • n=62 Participants	41.5 years STANDARD_DEVIATION 12.77 • n=124 Participants
Sex: Female, Male Female	27 Participants n=62 Participants	25 Participants n=62 Participants	52 Participants n=124 Participants
Sex: Female, Male Male	35 Participants n=62 Participants	37 Participants n=62 Participants	72 Participants n=124 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=62 Participants	4 Participants n=62 Participants	7 Participants n=124 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=62 Participants	58 Participants n=62 Participants	117 Participants n=124 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=62 Participants	0 Participants n=62 Participants	0 Participants n=124 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=62 Participants	0 Participants n=62 Participants	0 Participants n=124 Participants
Race (NIH/OMB) Asian	1 Participants n=62 Participants	0 Participants n=62 Participants	1 Participants n=124 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=62 Participants	1 Participants n=62 Participants	1 Participants n=124 Participants
Race (NIH/OMB) Black or African American	1 Participants n=62 Participants	2 Participants n=62 Participants	3 Participants n=124 Participants
Race (NIH/OMB) White	60 Participants n=62 Participants	59 Participants n=62 Participants	119 Participants n=124 Participants
Race (NIH/OMB) More than one race	0 Participants n=62 Participants	0 Participants n=62 Participants	0 Participants n=124 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=62 Participants	0 Participants n=62 Participants	0 Participants n=124 Participants
Region of Enrollment Netherlands	2 participants n=62 Participants	1 participants n=62 Participants	3 participants n=124 Participants
Region of Enrollment Hungary	1 participants n=62 Participants	1 participants n=62 Participants	2 participants n=124 Participants
Region of Enrollment United States	11 participants n=62 Participants	17 participants n=62 Participants	28 participants n=124 Participants
Region of Enrollment Czechia	3 participants n=62 Participants	2 participants n=62 Participants	5 participants n=124 Participants
Region of Enrollment Poland	43 participants n=62 Participants	38 participants n=62 Participants	81 participants n=124 Participants
Region of Enrollment Serbia	2 participants n=62 Participants	3 participants n=62 Participants	5 participants n=124 Participants
Baseline Total Mayo Score (TMS) and Modified Mayo Score (MMS) Baseline TMS Mean (Standard Deviation)	7.9 units on a scale STANDARD_DEVIATION 1.46 • n=62 Participants • One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.	7.8 units on a scale STANDARD_DEVIATION 1.77 • n=61 Participants • One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.	7.9 units on a scale STANDARD_DEVIATION 1.62 • n=123 Participants • One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.
Baseline Total Mayo Score (TMS) and Modified Mayo Score (MMS) Baseline MMS Mean (Standard Deviation)	6.0 units on a scale STANDARD_DEVIATION 1.38 • n=62 Participants • One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.	5.7 units on a scale STANDARD_DEVIATION 1.55 • n=62 Participants • One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.	5.8 units on a scale STANDARD_DEVIATION 1.47 • n=124 Participants • One subject in the placebo treatment arm did not have a complete Mayo score at baseline and therefore they were not included in this analysis population.

PRIMARY outcome

Timeframe: 8 weeks

Population: The analysis population consisted of all randomized subjects (Full Analysis Set).

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=62 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Number of Subjects Who Achieve Clinical Remission at Week 8 Using Modified Mayo Score.	7 Participants	12 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: The analysis population consisted of all randomized subjects (Full Analysis Set).

The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical remission on the total Mayo Score is defined as a total Mayo score of ≤ 2, with no individual subscore \> 1.

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=62 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Number of Subjects Who Achieve Clinical Remission at Week 8 Using the Total Mayo Score.	7 Participants	12 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: The analysis population consisted of all randomized subjects (Full Analysis Set).

The modified Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 9 points and consists of 3 subscores (stool frequency, rectal bleeding, endoscopy), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical response on the modified Mayo score at Week 8 was defined as a reduction from the baseline modified Mayo score of ≥ 2 points and ≥ 25%, and a decrease from baseline in rectal bleeding score of ≥ 1 point or absolute rectal bleeding score of ≤ 1 point.

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=62 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Number of Subjects With a Clinical Response on the Modified Mayo Score at Week 8.	32 Participants	36 Participants

SECONDARY outcome

Timeframe: 8 weeks

Population: The analysis population consisted of all randomized subjects (Full Analysis Set).

The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally. Clinical response on the total Mayo score at Week 8 was defined as a reduction from baseline total Mayo score of ≥ 3 points and ≥ 30%, and a decrease from baseline in rectal bleeding score of ≥ 1 point or absolute rectal bleeding score of ≤ 1 point.

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=62 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Number of Subjects With a Clinical Response on the Total Mayo Score at Week 8.	26 Participants	32 Participants

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: All randomized subjects who had an elevated baseline fecal calprotectin level of ≥ 250 µg/g and who had both a baseline and Week 8 value.

Fecal calprotectin is an indicator of inflammation in the colon with higher levels indicative of higher levels of inflammation.

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=51 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=44 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Percent Change From Baseline to Week 8 in Fecal Calprotectin in Subjects With Baseline Fecal Calprotectin ≥ 250 µg/g	-35.22 percent change from baseline Standard Error 13.81	9.37 percent change from baseline Standard Error 15.07

SECONDARY outcome

Timeframe: Baseline to Week 8

Population: All randomized subjects randomized who had TMS scores at baseline and Week 8.

Analyzes the change in total Mayo score score between baseline and Week 8 for all randomized subjects who had total Mayo score scores at both baseline and Week 8. The total Mayo score is a tool designed to measure disease activity for ulcerative colitis. Scoring ranges from 0 to 12 points and consists of 4 subscores (stool frequency, rectal bleeding, endoscopy, physicians global assessment), each graded 0 to 3 with higher score indicating more severe disease activity. Endoscopy scoring was performed centrally.

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=59 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=58 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Percent Change From Baseline in Total Mayo Score at Week 8.	-2.49 Percent Change from baseline Standard Error 0.33	-2.67 Percent Change from baseline Standard Error 0.33

OTHER_PRE_SPECIFIED outcome

Timeframe: 10 weeks

Population: Safety Set, consisting of all randomized subjects who took at least one dose of study drug.

Adverse events (AEs) were collected from the time a subject signed the informed consent. Treatment-emergent adverse events (TEAEs) are AEs occurring or worsening after the first dose of study drug (LYC-30937-EC 25 mg or placebo). Adverse event 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.

Outcome measures

Outcome measures
Measure	LYC-30937-EC 25 mg PO QD n=62 Participants LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 Participants Matching placebo by mouth once daily for 8 weeks Placebo
Number of Subjects With Type of Adverse Events (AEs) Serious Adverse Events (SAEs) and AEs That Led to Discontinuation of Treatment. Subjects with ≥ 1 TEAE	22 Participants	27 Participants
Number of Subjects With Type of Adverse Events (AEs) Serious Adverse Events (SAEs) and AEs That Led to Discontinuation of Treatment. Subjects with ≥ 1 TESAE	1 Participants	3 Participants
Number of Subjects With Type of Adverse Events (AEs) Serious Adverse Events (SAEs) and AEs That Led to Discontinuation of Treatment. Subjects with TEAE leading to discontinuation	0 Participants	2 Participants

Adverse Events

LYC-30937-EC 25 mg PO QD

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Placebo PO QD

Serious events: 3 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LYC-30937-EC 25 mg PO QD n=62 participants at risk LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 participants at risk Matching placebo by mouth once daily for 8 weeks Placebo
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	1.6% 1/62 • Number of events 1 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.	0.00% 0/62 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.
Infections and infestations Clostridium difficile infection	0.00% 0/62 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.	1.6% 1/62 • Number of events 1 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.
Renal and urinary disorders Renal colic	0.00% 0/62 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.	1.6% 1/62 • Number of events 1 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/62 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.	1.6% 1/62 • Number of events 1 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.

Other adverse events

Other adverse events
Measure	LYC-30937-EC 25 mg PO QD n=62 participants at risk LYC-30937-EC 25 mg by mouth once daily for 8 weeks LYC-30937-EC	Placebo PO QD n=62 participants at risk Matching placebo by mouth once daily for 8 weeks Placebo
Nervous system disorders Headache	9.7% 6/62 • Number of events 6 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.	8.1% 5/62 • Number of events 6 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.
Gastrointestinal disorders Abdominal pain	6.5% 4/62 • Number of events 4 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.	9.7% 6/62 • Number of events 8 • Adverse events were collected from the time a subject signed informed consent through the Week 10 follow-up visit. SAEs occurring after the last study visit that were determined by the investigator to be related to study drug were to be reported.

Additional Information

H. Jeffrey Wilkins, MD, Chief Medical Officer

Lycera Corp.

Phone: 484-243-6222

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Center results cannot be submitted for publication before results of multicenter study are published unless it is more than 1 year 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.
Publication restrictions are in place

Restriction type: OTHER