Pharmacokinetics of Cobitolimod Enemas in Participants with active Ulcerative Colitis

Phase 1

Conditions: Moderate to Severe Active Ulcerative Colitis
MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856
Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Registration Number: EUCTR2021-003023-14-SE

Lead Sponsor: InDex Pharmaceuticals AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 20

Inclusion Criteria

1.Willing and able to give written informed consent for participation in the study.
2.Male or female patient aged =18 years.
3.Established diagnosis of UC, with minimum time from diagnosis of at least 3 months before screening.
4.Moderate to severe active UC (disease should extend 15 cm or more above the anal verge) determined by a 3-component Mayo score 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 frequency and rectal bleeding subscores each =1.
5.Clinically acceptable medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
6.Women only:
WOCBP must practice abstinence (only allowed when this is the preferred and usual lifestyle of the patient) or must agree to use a highly effective method of contraception with a failure rate of < 1% to prevent pregnancy (combined [oestrogen and progestogen containing] hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal], progestogen-only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable], intrauterine device [IUD] or intrauterine hormone-releasing system [IUS]) from at least 4 weeks prior to dose to 4 weeks after last dose. Female patients must refrain from donating eggs from the date of dosing until 3 months after dosing with the IMP. Their male partner must agree to use a condom during the same time frame if he has not undergone vasectomy.
Women of non-childbearing potential are defined as pre-menopausal females who are sterilised (tubal ligation or permanent bilateral occlusion of fallopian tubes); or females who have undergone hysterectomy or bilateral oophorectomy; or post-menopausal defined as 12 months of amenorrhea (in questionable cases a blood sample with detection of follicle stimulating hormone [FSH] 25-140 IE/L is confirmatory).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion Criteria

1. Suspicion of differential diagnosis such as Crohn’s enterocolitis, ischaemic colitis, radiation colitis, indeterminate colitis, infectious colitis, diverticular disease, associated colitis, microscopic colitis, massive pseudopolyposis or non-passable stenosis.
2. Acute fulminant UC, toxic megacolon and/or signs of systemic toxicity.
3. Have failed treatment with more than three advanced therapies (infliximab, adalimumab, golimumab, vedolizumab, ustekinumab or tofacitinib) of two different therapeutic classes (anti-TNF, anti-integrins, anti-IL12/23, JAKinhibitors, or other approved advanced therapies for UC).
4. Have had surgery for treatment of UC.
5. History of malignancy, unless treated with no relapse of the disease and = 5 years since last treatment (cured) or treated (cured) basal cell or squamous cell in situ carcinoma.
6. Serious known active infection including history of latent or active tuberculosis, documented history of past or current tuberculosis, or living with or having frequent close contact with people with active tuberculosis or with a positive tuberculosis test according to current regulations for 12 weeks preceding randomisation. Serious infections include, but is not limited to, HIV, hepatitis B, or hepatitis C infections.
7. Gastrointestinal infections including positive Clostridium difficile stool assay (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).
8. History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant’s ability to participate in the study.
9. Concomitant or planned treatment with cyclosporine, methotrexate, tacrolimus, or advanced therapies such as infliximab, adalimumab, golimumab, vedolizumab,ustekinumab or tofacitinib, or similar immunosuppressants and immunomodulators at enrolment.
Any prior treatment with such drugs must have been discontinued at least 8 weeks prior to Visit 1 (except for ustekinumab, which must have been discontinued at least 12 weeks prior to Visit 1) or have non-measurable serum concentration levels.
10. Treatment with rectal GCS, 5-ASA/SP or tacrolimus within 2 weeks before Visit 1.
11. Long-term treatment (>14 days) with antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs) within 2 weeks prior to Visit 1 (one short treatment regimen for antibiotics, occasional use of NSAIDs and low dose NSAIDs as prophylactic therapy is allowed).
12. Females who are lactating or have a positive serum pregnancy test at Visit 1.
13. Any planned major surgery within the duration of the study.
14. Planned treatment or treatment with another investigational drug within 3 months prior to Day -1.

15. Plasma donation within one month of screening or blood donation (or corresponding blood loss) during the three months prior to screening.
16. Investigator considers the participant unlikely to comply with study procedures, restrictions and requirements.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess PK properties of cobitolimod in plasma after administration of cobitolimod enema in participants with active UC and in remission.;Secondary Objective: To assess safety and tolerability of cobitolimod after administration of cobitolimod enema in participants with active UC and in remission.<br><br>To assess blood biomarkers of cobitolimod after administration of cobitolimod enema in participants with active UC and in remission.<br>;Primary end point(s): •Maximum observed plasma concentration (Cmax)<br>•Time to Cmax (Tmax)<br>•Area under the curve from 0 to timepoint t (AUCt)<br>•AUC from 0 to infinity (AUCinf) <br>• Half-life (T1/2);Timepoint(s) of evaluation of this end point: Visit 2, visit 3 and visit 4.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •Frequency, intensity and seriousness of adverse events (AEs)<br>•Clinically significant changes in electrocardiogram (ECG), vital signs, <br> safety laboratory parameters, physical examinations<br>•Significant changes in blood biomarkers<br>;Timepoint(s) of evaluation of this end point: All visits: Visit 1 - visit 5

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