A Study Evaluating the Efficacy and Safety of ST-0529 in Subjects With Moderately to Severely Active Ulcerative Colitis

• Register: ClinicalTrials.gov
• Last refreshed on: 17 May 2021
• Main ID: NCT03844932
• Date of registration: 31/01/2019
• Prospective Registration: No
• Primary sponsor: Sublimity Therapeutics Holdco Limited
• Public title: A Study Evaluating the Efficacy and Safety of ST-0529 in Subjects With Moderately to Severely Active Ulcerative Colitis
• Scientific title: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of ST-0529 in Subjects With Moderately to Severely Active Ulcerative Colitis
• Date of first enrolment: January 24, 2019
• Target sample size: 235
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03844932
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

Belarus, Bulgaria, Canada, France, Germany, Hungary, Ireland, Israel, Italy, Poland, Romania, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Sponsor Responsible Medical Officer
• Affiliation: Sublimity Therapeutics (HoldCo) Ltd

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Male and female adult subjects 18 to 75 years old, inclusive.

2. Willing to provide written informed consent and to be compliant with the schedule of
study visits and protocol assessments.

3. Diagnosis of UC established at least 3 months prior to the Baseline visit, by clinical
and endoscopic evidence (colonoscopy or flexible sigmoidoscopy)

4. Moderately to severely active UC defined as the 3-Component Adapted Mayo Score of 5-9,
inclusive, with an endoscopic sub-score of = 2 (from central reading), and a rectal
bleeding sub-score of = 1, as determined 10 days (± 3 days) prior to Baseline.

5. Evidence of active UC, confirmed histologically (from local read), extending proximal
to the rectum with = 15 cm of involved colon.

6. At Screening, a colonoscopy will be required if the subject has had extensive colitis
or pancolitis of > 8 years duration or left-sided colitis of > 12 years duration but
has not had a colonoscopy within 1 year of the initial screening date. If the subject
has had a colonoscopy within 1 year of the initial screening date, a flexible
sigmoidoscopy may be used.

7. Subjects presenting at Screening with moderately to severely active UC demonstrating
an inadequate response or loss of response or intolerance/medical contraindication to
at least one of the following conventional therapies for UC:

a. Corticosteroids:

i. Signs and symptoms of active disease despite treatment with an adequate dose (e.g.,
prednisolone > 40 mg/day or equivalent) over a period of 4 weeks for oral therapy or
intravenously (IV) for up to 1 week or = 9 mg/day oral budesonide;

OR

ii. Unable to reduce corticosteroids below the equivalent of prednisolone 10 mg daily
orally within 3 months of starting steroids or having experienced a relapse within 3
months of stopping steroids;

OR

iii. History of, or current intolerance to corticosteroids (including, but not limited
to Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection).

b. Immunomodulators:

i. Signs and symptoms of active disease despite at least 3 months of treatment with a
sufficient dose (oral azathioprine = 1.5 mg/kg or 6-mercaptopurine [6-MP] = 0.75
mg/kg);

OR

ii. History of, or current dose-limiting toxicity associated with use of the agent
(e.g., but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver
function test [LFT] abnormalities, lymphopenia, TPMT genetic mutation, infection).

c. Anti-tumor necrosis factor (anti-TNF) agents:

i. Signs and symptoms of active disease despite treatment with a single anti-TNF
agent. Treatment failure is defined as a relapse after an initial response to therapy
as follows:

- Infliximab: At least 4 infusions of at least 5 mg/kg within a 14-week timeframe
for induction and maintenance;

- Adalimumab: Induction regimen incorporating 160 mg at Week 0 (four 40 mg
injections in one day or two 40 mg injections per day for two consecutive days)
and 80 mg at Week 2, followed by maintenance treatment of 40 mg every other week
up to at least Week 8;

- Golimumab: Induction regimen incorporating 200 mg subcutaneous (sc) injection at
Week 0, followed by 100 mg at Week 2 and then maintenance treatment of 50 mg or
100 mg (weight dependent) every 4 weeks after completion of the induction regimen
up to at least Week 12;

OR

ii. History of, or current intolerance (with an initial response), defined as the
presence of clinically significant side-effects, including infusion-related
hypersensitivity.

d. Vedolizumab:

i. Signs and symptoms of active disease despite a history of at least one induction
regimen, defined as at least a 14-week (10 weeks in the EU) induction consisting of
300 mg IV at Weeks 0, 2 and 6.

OR

ii. History of intolerance to vedolizumab including, but not limited to, serious
infections, hepatotoxicity, heart failure, allergic reactions, or any other condition
that contributed to discontinuation of the agent.

8. Subjects receiving oral corticosteroids for the treatment of UC must be on a stable
dose of = 40 mg/day (prednisolone or equivalent), or = 9 mg/day budesonide. This dose
must be stable from the initial Screening visit until 1 week after the initiation of
study treatment.

9. Subjects receiving oral 5-ASA must be on a stable dose from the initial Screening
visit until the end of the study.

10. Subjects willing to cease the use of any therapeutic enema or suppository or foams,
other than that required in preparation for study-mandated colonoscopy/flexible
sigmoidoscopies, from the initial Screening visit until the end of the study.

11. Subjects willing to cease use of azathioprine or 6-MP from the initial Screening visit
until the end of the study.

12. Negative serum pregnancy test in females of childbearing potential at Screening.

13. If female and of childbearing potential, must agree to be sexually abstinent or use
one of the following highly effective methods of birth control from the initial
Screening visit until 30 days after the last dose of study drug is administered:

1. Hormonal contraceptives (e.g., combined oral contraceptives, patch, vaginal ring,
injectables, and implants);

2. Intrauterine contraceptive system;

3. Surgical sterilization or partner sterile (must have documented proof);

AND

One of the following effective methods of birth control:

1. Male/female condom;

2. Cervical cap with spermicide;

3. Diaphragm with spermicide;

4. Contraceptive sponge.

14. Male subjects must be either surgically sterile (must have documented proof), agree to
be sexually inactive or use a double-barrier method of birth control (e.g., condom and
diaphragm with spermicide, condom with cervical cap and spermicide) from first study
drug administration until 90 days after final drug administration.

Exclusion Criteria:

If a subject has any of the following criteria, they will be excluded from the study:

1. Subjects without previous treatment for UC.

2. Ulcerative colitis limited to rectum (ulcerative proctitis).

3. Evidence of acute severe colitis with toxic megacolon, abdominal abscess, bowel
stricture or bowel perforation.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Colitis, Ulcerative

Intervention(s)

Drug: ST-0529

Primary Outcome(s)

Clinical Remission at Week 12 [Time Frame: Week 12]

Secondary Outcome(s)

Corticosteroid-free clinical remission at Week 12 [Time Frame: Week 12]

Changes from baseline in individual Adapted Mayo sub-scores at Week 12 [Time Frame: Week 12]

Endoscopic Healing at Week 12 [Time Frame: Week 12]

Clinical Response at Week 12 [Time Frame: Week 12]

Corticosteroid-free clinical response at Week 12 [Time Frame: Week 12]

Secondary ID(s)

CYC-202

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Dr. Falk Pharma GmbH