Colitis, Ulcerative
Conditions
Keywords
ulcerative colitis, efficacy, safety
Brief summary
The purpose of the study was to assess preliminary efficacy, safety, and tolerability of LYS006 in adult patients with mild to moderate ulcerative colitis and to determine if LYS006 has an adequate clinical profile for further development in this indication.
Detailed description
This was a randomized, placebo-controlled, subject and investigator blinded, multicenter, non-confirmatory, parallel group, proof of concept study in patients with mild to moderate ulcerative colitis. This study consisted of a screening period of up to 4 weeks, and a 8 week treatment period followed by a 30 day post treatment period safety follow up. The maximum study duration for each participant including the 4 week screening period was 16 weeks. At the beginning of the treatment period, subjects were randomized to one of the two following treatment groups in 2:1 ratio * LYS006 * matching placebo
Interventions
DRUGLYS006
capsule for oral use
DRUGPlacebo
capsule for oral use
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Subject and investigator blinded via randomization
Intervention model description
This is a randomized, placebo-controlled, subject and investigator blinded, multicenter, non-confirmatory, parallel group, proof of concept study in patients with mild to moderate ulcerative colitis. This study consists of a screening period of up to 4 weeks, and a 8 week treatment period followed by a 30 day post treatment period safety follow up. The maximum study duration for each such including the 4 week screening period is 16 weeks. At the beginning of the treatment period, subjects will be randomized to one of the two following treatment groups in 2:1 ratio: * LYS006 * matching placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male and female subjects 18-75 years of age with an established diagnosis of ulcerative colitis at least 3 months prior to screening are eligible for the study. * Patients must have active disease with a full Mayo Score between 5 and 10 (inclusive) with an endoscopy score of 2 or 3; rectal bleeding and stool frequency scores 1 to 3 and a physician's global assessment of 1 or 2. * Patients must have responded inadequately to conventional therapy with oral 5-ASA prior to screening. Key
Exclusion criteria
* Has previous diagnosis with Crohn's disease, indeterminate colitis, microscopic colitis or acute diverticulitis based on medical history. * History of toxic megacolon, abdominal abscess, symptomatic colonic stricture, or stoma; history or is at risk of colectomy. * Treatment with biologics within 3 months or 5 half-lives (whichever is longer) prior to screening endoscopy, non-biologics advanced therapies within 4 weeks prior to screening endoscopy, systemic immunosuppressant or immunomodulator within 6 week, topical treatment with 5-ASA or steroids within 2 weeks prior to screening endoscopy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Remission Rate at the End of the Study Treatment | Week 8 | The Mayo score is an instrument designed to measure activity of ulcerative colitis. The Mayo score comprises of four sub scores: stool frequency, rectal bleeding, endoscopic findings and the Physician's Global Assessment (PhGA). Each sub score is graded from 0 to 3 with higher scores indicating more severe disease. The full Mayo score is the sum of four sub scores, ranging from 0 to 12. Clinical remission is defined as a full Mayo score of 2 points or lower, with no individual subscore exceeding one point. The clinical remission rate is expressed as percentage of participants. The binary endpoint of clinical remission rate (Yes/No) at the EoT visit was modelled with binomial distribution and analyzed via the Bayesian approach with baseline total Mayo score and treatment group as explanatory variables, to compare the remission rates between the LYS006 and placebo groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 86 days. | Number of participants with treatment emergent AEs, AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation. |
Countries
Bulgaria, Czechia, Germany, Poland, Russia, Slovakia
Participant flow
Recruitment details
Participants took part in 9 investigative sites in 6 countries.
Pre-assignment details
After signing informed consent, screening evaluations took place from Day -28 to Day -1. During that period all safety and other assessments were performed to evaluate eligibility. Eligible patients returned for the Baseline visit on Day 1. Eligibility was confirmed prior to randomization and required baseline assessments were completed prior to dosing on Day 1.
Participants by arm
| Arm | Count |
|---|---|
| LYS006 20mg LYS006 20mg oral dose, twice daily | 16 |
| Placebo Placebo oral dose, twice daily | 7 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | LYS006 20mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 38.3 years STANDARD_DEVIATION 12.2 | 45.7 years STANDARD_DEVIATION 12.37 | 40.6 years STANDARD_DEVIATION 12.46 |
| Race/Ethnicity, Customized White | 16 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 7 | 0 / 23 |
| other Total, other adverse events | 7 / 16 | 5 / 7 | 12 / 23 |
| serious Total, serious adverse events | 0 / 16 | 0 / 7 | 0 / 23 |
Outcome results
Primary
Clinical Remission Rate at the End of the Study Treatment
The Mayo score is an instrument designed to measure activity of ulcerative colitis. The Mayo score comprises of four sub scores: stool frequency, rectal bleeding, endoscopic findings and the Physician's Global Assessment (PhGA). Each sub score is graded from 0 to 3 with higher scores indicating more severe disease. The full Mayo score is the sum of four sub scores, ranging from 0 to 12. Clinical remission is defined as a full Mayo score of 2 points or lower, with no individual subscore exceeding one point. The clinical remission rate is expressed as percentage of participants. The binary endpoint of clinical remission rate (Yes/No) at the EoT visit was modelled with binomial distribution and analyzed via the Bayesian approach with baseline total Mayo score and treatment group as explanatory variables, to compare the remission rates between the LYS006 and placebo groups.
Time frame: Week 8
Population: The PD analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LYS006 20mg | Clinical Remission Rate at the End of the Study Treatment | 8.95 Percentage of participants |
| Placebo | Clinical Remission Rate at the End of the Study Treatment | 12.24 Percentage of participants |
p-value: 0.31490% CI: [-18.02, 13.23]Bayesian analysis
p-value: 0.03790% CI: [-18.02, 13.23]Bayesian analysis
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Number of participants with treatment emergent AEs, AEs led to study treatment discontinuation, SAEs and SAEs led to study treatment discontinuation.
Time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days post treatment, up to a maximum duration of approximately 86 days.
Population: The safety analysis set included all participants that received any study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| LYS006 20mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 7 Participants |
| LYS006 20mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one SAE | 0 Participants |
| LYS006 20mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE leading to discontinuation | 2 Participants |
| LYS006 20mg | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE leading to discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE leading to discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one AE | 5 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE leading to discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | At least one SAE | 0 Participants |