Clinical trial NCT02888379: Phase 2a Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Ulcerative Colitis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ulcerative Colitis
Lead sponsor: Topivert Pharma Ltd
Sponsor class: INDUSTRY
First posted: 2016-09-05
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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

Eligibility criteria: Key Inclusion Criteria:

* Diagnosis of UC of at least 3 months duration
* Active UC with a Partial Mayo Clinic Score of 4 to 8 at randomization

Key Exclusion Criteria:

* Receiving any rectally administered medication
* Use of biologic agents within 3 months prior to Screening endoscopy
* Use of IV corticosteroids within 4 weeks prior to Screening endoscopy
* Use of oral corticosteroids at a dose \>30 mg/day (or budesonide \>9 mg/day).
* Patients who have started receiving immune suppressants within 3 months of the Screening endoscopy should not be included.
* Known or suspected pancolitis (unless on oral 5-ASA, steroids or permitted immunomodulators)
* Known or suspected Crohn's disease, indeterminate colitis, microscopic colitis, ischaemic colitis, or radiation-induced colitis, based on medical history, endoscopy, and/or histological findings
* Extensive (\>50%) colonic resection or colectomy, or prior history of toxic megacolon within 3 months of Screening
* Patient has active serious infection (e.g., sepsis, pneumonia, abscess) or has had a serious infection (resulting in hospitalisation or requiring parenteral antibiotic treatment) within 6 weeks prior to IMP administration
* Patients testing positive of Clostridium difficile toxin or confirmed with bacterial or parasitical GI infections at Screening

Primary outcomes:
measure: Efficacy as measured by the Mayo Clinic modified endoscopic subscore
timeFrame: After 4 consecutive weeks of daily bedtime treatment
Secondary outcomes:
measure: Safety as measured by adverse events
timeFrame: To 1 week after the last dose
measure: Safety as measured by vital signs
timeFrame: To 1 week after the last dose
measure: Safety as measured by ECGs
timeFrame: To 1 week after the last dose
measure: Safety as measured by clinical laboratory tests
timeFrame: To 1 week after the last dose
measure: Efficacy as measured by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score
timeFrame: After 4 consecutive weeks of daily bedtime treatment
measure: Efficacy as measured by Partial Mayo Clinic score (i.e., the sum of the endoscopic, rectal bleeding, and stool frequency subscores)
timeFrame: After 4 consecutive weeks of daily bedtime treatment
measure: Efficacy as measured by endoscopic healing (indicated by the Mayo Clinic modified endoscopic subscore)
timeFrame: After 4 consecutive weeks of daily bedtime treatment
measure: Efficacy as measured by rectal bleeding (indicated by the Mayo Clinic rectal bleeding subscore)
timeFrame: After 4 consecutive weeks of daily bedtime treatment
Other outcomes:
Locations:
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Brno
country: Czechia
city: Litomerice
country: Czechia
city: Olomouc
country: Czechia
city: Praha
country: Czechia
city: Budapest
country: Hungary
city: Gyongyos
country: Hungary
city: Gyor
country: Hungary
city: Gyula
country: Hungary
city: Szeged
country: Hungary
city: Szekesfehervar
country: Hungary
city: Vac
country: Hungary
city: Daugavpils
country: Latvia
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Bydgoszcz
country: Poland
city: Knurow
country: Poland
city: Skierniewice
country: Poland
city: Sopot
country: Poland
city: Warsaw
country: Poland
city: Wroclaw
country: Poland
city: Kherson
country: Ukraine
city: Kyiv
country: Ukraine
city: Odessa
country: Ukraine
city: Temopil
country: Ukraine
city: Zaporizhzhia
country: Ukraine
city: London
country: United Kingdom
Study officials:
affiliation: Oxford University Hospitals Trust, John Radcliffe Hospital, Oxford, UK,
name: Simon Travis, FRCP
role: PRINCIPAL_INVESTIGATOR
References: