Phase 2a Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Ulcerative Colitis (TOP2)
|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: NCT02888379|
Recruitment Status : Completed
First Posted : September 5, 2016
Last Update Posted : July 7, 2017
|Condition or disease||Intervention/treatment||Phase|
|Ulcerative Colitis||Drug: TOP1288 Drug: Placebo (for TOP1288)||Phase 2|
TOP1288, the first in a new class of agents called narrow spectrum protein kinase inhibitors (NSKIs), is being developed as a novel, non-absorbed treatment for ulcerative colitis (UC). UC is a disease of unknown cause characterised by inflammation of the lining of the large intestine and manifesting with abdominal pain and bloody diarrhoea. TOP1288 given rectally has a local anti-inflammatory action in experimental models of UC.
A Phase I placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study of TOP1288 conducted in 61 healthy volunteers demonstrated that rectal administration of TOP1288 at doses up to 200 mg BID for 4 days was safe and well tolerated, with minimal systemic absorption. TOP1288 200 mg, administered once daily, therefore offers the potential for a safe and effective novel approach to treating patients with this serious condition.
This Phase 2a proof-of-concept study will evaluate the 200 mg daily dose of TOP1288, based on its favourable tolerability in the Phase 1 study. It will be administered as TOP1288 200 mg Rectal Solution compared against Placebo Rectal Solution, which contains all non-active excipients present in the active solution. This is a randomised, double-blind, placebo-controlled multicentre study designed to evaluate the safety/tolerability and efficacy of TOP1288 200 mg Rectal Solution following once-daily bedtime treatment for 4 consecutive weeks. The study will include approximately 40 sites in Europe. Randomization to study treatment will be 2:1, with approximately 40 subjects randomised to TOP1288 and approximately 20 subjects randomised to placebo.
The Screening period will be up to 28 days prior to the first day of dosing with double-blind study treatment (Visit 1). A central reading facility will be used to determine eligibility based upon the Screening flexible sigmoidoscopy.
Visit 2 is scheduled for Day 7 of dosing, and Visit 3 for Day 29 of dosing. There will be a 1-week safety follow-up period after Visit 3. The total duration of study participation for a given subject will be up to ~65 days or 9 weeks
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||77 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Symptomatic Ulcerative Colitis Patients With Moderate to Severe Disease Activity|
|Actual Study Start Date :||September 2016|
|Actual Primary Completion Date :||June 28, 2017|
|Actual Study Completion Date :||June 28, 2017|
Experimental: TOP1288 200 mg Rectal Solution
TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks
Placebo Comparator: Placebo Rectal Solution
Placebo (for TOP1288) Rectal Solution Once Daily for 4 Weeks
Drug: Placebo (for TOP1288)
- Efficacy as measured by the Mayo Clinic modified endoscopic subscore [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
- Safety as measured by adverse events [ Time Frame: To 1 week after the last dose ]
- Safety as measured by vital signs [ Time Frame: To 1 week after the last dose ]
- Safety as measured by ECGs [ Time Frame: To 1 week after the last dose ]
- Safety as measured by clinical laboratory tests [ Time Frame: To 1 week after the last dose ]
- Efficacy as measured by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
- Efficacy as measured by Partial Mayo Clinic score (i.e., the sum of the endoscopic, rectal bleeding, and stool frequency subscores) [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
- Efficacy as measured by endoscopic healing (indicated by the Mayo Clinic modified endoscopic subscore) [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
- Efficacy as measured by rectal bleeding (indicated by the Mayo Clinic rectal bleeding subscore) [ Time Frame: After 4 consecutive weeks of daily bedtime treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02888379
|London, United Kingdom|
|Principal Investigator:||Simon Travis, FRCP||Oxford University Hospitals Trust, John Radcliffe Hospital, Oxford, UK,|