Pharmacokinetics of Cobitolimod Enemas in Participants With Active Ulcerative Colitis

Inclusion Criteria:

1. Willing and able to give written informed consent for participation in the study.
2. Male or female participant aged ≥18 years.
3. Established diagnosis of UC, with minimum time from diagnosis of at least 3 monthsbefore screening.
4. Moderate to severe active left-sided UC (disease should extend 15 cm or more above theanal verge and may extend beyond the splenic flexure) determined by a 3-component Mayoscore of 5 to 9 with an endoscopic subscore ≥2 (in sigmoid or descending segments)assessed by the Investigator's reading of the endoscopy, and with a stool frequencyand rectal bleeding subscores each ≥1.
5. Clinically acceptable medical history, physical findings, vital signs, ECG andlaboratory values at the time of screening, as judged by the Investigator.
6. Women only: WOCBP must practice abstinence (only allowed when this is the preferredand usual lifestyle of the participant) or must agree to use a highly effective methodof contraception with a failure rate of < 1% to prevent pregnancy (combined [oestrogenand progestogen containing] hormonal contraception associated with inhibition ofovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraceptionassociated with inhibition of ovulation [oral, injectable, implantable], intrauterinedevice [IUD] or intrauterine hormone-releasing system [IUS]) from at least 4 weeksprior to dose to 4 weeks after last dose. Women of non-childbearing potential are defined as pre-menopausal females who aresterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or femaleswho have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12months of amenorrhea (in questionable cases a blood sample with detection of folliclestimulating hormone [FSH] 25-140 IE/L is confirmatory)

Exclusion Criteria:

• 1. Suspicion of differential diagnosis such as Crohn's enterocolitis, ischaemiccolitis, radiation colitis, indeterminate colitis, infectious colitis, diverticulardisease, associated colitis, microscopic colitis, massive pseudopolyposis ornon-passable stenosis.

2. Acute fulminant UC, toxic megacolon and/or signs of systemic toxicity. 3. Havefailed treatment with more than three advanced therapies (infliximab, adalimumab,golimumab, vedolizumab, ustekinumab or tofacitinib) of two different therapeuticclasses (anti-TNF, anti-integrins, anti-IL12/23, JAK-inhibitors, or other approvedadvanced therapies for UC).
3. Have had surgery for treatment of UC. 5. History of malignancy, unless treated withno relapse of the disease and ≥ 5 years since last treatment (cured) or treated (cured) basal cell or squamous cell in situ carcinoma.
4. Serious known active infection e.g., any positive result on screening for serumhepatitis B surface antigen, hepatitis C virus antibodies and HIV.
5. Gastrointestinal infections including positive Clostridium difficile stool assay (local laboratory reports must be available in accordance with normal clinic practice,to confirm that the current episode of disease exacerbation is not due to infection).
6. History of any clinically significant disease or disorder which, in the opinion ofthe Investigator, may either put the participant at risk because of participation inthe study, or influence the results or the participant's ability to participate in thestudy.
7. Concomitant or planned treatment with cyclosporine, methotrexate, tacrolimus, oradvanced therapies such as infliximab, adalimumab, golimumab, vedolizumab, ustekinumabor tofacitinib, or similar immunosuppressants and immunomodulators at enrolment. Anyprior treatment with such drugs must have been discontinued at least 8 weeks prior toVisit 1 (except for ustekinumab, which must have been discontinued at least 12 weeksprior to Visit 1) or have non-measurable serum concentration levels.
8. Treatment with rectal GCS, 5-ASA/SP or tacrolimus within 2 weeks before Visit 1.
9. Long-term treatment (>14 days) with antibiotics or non-steroidal anti-inflammatorydrugs (NSAIDs) within 2 weeks prior to Visit 1 (one short treatment regimen forantibiotics, occasional use of NSAIDs and low dose NSAIDs as prophylactic therapy isallowed).
10. Females who are lactating or have a positive serum pregnancy test at Visit 1.
11. Any planned major surgery within the duration of the study. 14. Planned treatmentor treatment with another investigational drug within 3 months prior to Day -1.
12. Plasma donation within one month of screening or blood donation (or correspondingblood loss) during the three months prior to screening.
13. Investigator considers the participant unlikely to comply with study procedures,restrictions and requirements.