Ulcerative ColitisPhase 2TOP2NCT02888379
Phase 2a Study to Evaluate the Safety/Tolerability and Efficacy of TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks in Ulcerative Colitis
A Phase 2 study testing TOP1288 in people with Ulcerative Colitis, run by Topivert Pharma Ltd at 28 sites in 8 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- TOP1288
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 77 participants
- Where
- 28 sitesin 8 countries
- Study dates
- Sep 2016to 28 Jun 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of UC of at least 3 months duration
- Active UC with a Partial Mayo Clinic Score of 4 to 8 at randomization
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
28 sites in 8 countries.
28 sites in 8 countries
Hungary7 sites
Study site
Budapest
Study site
Gyöngyös
Study site
Győr
Study site
Gyula
Study site
Szeged
Study site
Székesfehérvár
Study site
Vác
Poland6 sites
Study site
Bydgoszcz
Study site
Knurów
Study site
Skierniewice
Study site
Sopot
Study site
Warsaw
Study site
Wroclaw
Ukraine5 sites
Study site
Kherson
Study site
Kyiv
Study site
Odesa
Study site
Temopil
Study site
Zaporizhzhya
Czechia4 sites
Study site
Brno
Study site
Litoměřice
Study site
Olomouc
Study site
Prague
About this study
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
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
Read the 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
- Conditions
- Ulcerative Colitis
- Being tested
- TOP1288, Placebo (for TOP1288)
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TOP1288Drug
Placebo (for TOP1288)Drug
| Study group | Role | What they receive |
|---|---|---|
| TOP1288 200 mg Rectal Solution | Experimental | TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks Receives: Drug: TOP1288 |
| Placebo Rectal Solution | Placebo comparator | Placebo (for TOP1288) Rectal Solution Once Daily for 4 Weeks Receives: Drug: Placebo (for TOP1288) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy as measured by the Mayo Clinic modified endoscopic subscore
Measured: After 4 consecutive weeks of daily bedtime treatment
Secondary outcomes (8)
Safety as measured by adverse events
Measured: To 1 week after the last dose
Safety as measured by vital signs
Measured: To 1 week after the last dose
Safety as measured by ECGs
Measured: To 1 week after the last dose
Safety as measured by clinical laboratory tests
Measured: To 1 week after the last dose
Efficacy as measured by Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score
Measured: 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)
Measured: After 4 consecutive weeks of daily bedtime treatment
Efficacy as measured by endoscopic healing (indicated by the Mayo Clinic modified endoscopic subscore)
Measured: After 4 consecutive weeks of daily bedtime treatment
Efficacy as measured by rectal bleeding (indicated by the Mayo Clinic rectal bleeding subscore)
Measured: After 4 consecutive weeks of daily bedtime treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion28 Jun 2017
- Study completion28 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- Topivert Pharma Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Simon Travis, FRCP, Principal investigator, Oxford University Hospitals Trust, John Radcliffe Hospital, Oxford, UK,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02888379
- Sponsor's protocol ID
- TOP1288-TV-02
- Acronym
- TOP2
- Status last verified
- Jul 2017
- First submitted
- 30 Aug 2016
- Last updated
- 7 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02888379
- Acronym / sponsor ID
- TOP2 / TOP1288-TV-02
- Conditions
- Ulcerative Colitis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 77 participants (actual)
- Lead sponsor
- Topivert Pharma LtdIndustry (pharma, biotech, devices)
- Study start
- Sep 2016 (actual)
- Primary completion
- 28 Jun 2017 (actual)
- Study completion
- 28 Jun 2017 (actual)
- First posted
- 5 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| TOP1288 200 mg Rectal Solution | Experimental | Drug: TOP1288TOP1288 200 mg Rectal Solution Once Daily for 4 Weeks |
| Placebo Rectal Solution | Placebo comparator | Drug: Placebo (for TOP1288)Placebo (for TOP1288) Rectal Solution Once Daily for 4 Weeks |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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 (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TOP1288 | Drug | TOP1288 200 mg Rectal Solution |
| Placebo (for TOP1288) | Drug | Placebo Rectal Solution |
Primary outcome
Efficacy as measured by the Mayo Clinic modified endoscopic subscore
Time frame: After 4 consecutive weeks of daily bedtime treatment
8 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Simon Travis, FRCP principal investigator
Oxford University Hospitals Trust, John Radcliffe Hospital, Oxford, UK,
28 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TOP1288 in people with Ulcerative Colitis, run by Topivert Pharma Ltd at 28 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Hungary, Poland, Ukraine, Czechia, Bulgaria and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy as measured by the Mayo Clinic modified endoscopic subscore (time frame: After 4 consecutive weeks of daily bedtime treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2017.