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Pharmacokinetics of Cobitolimod Enemas in Participants With Active Ulcerative Colitis

Primary Purpose

Ulcerative Colitis

Status
Recruiting
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Cobitolimod 500mg
Sponsored by
InDex Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 months before screening.
  4. Moderate to severe active left-sided UC (disease should extend 15 cm or more above the anal verge and may extend beyond the splenic flexure) 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 participant) 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.

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)

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, JAK-inhibitors, 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 e.g., any positive result on screening for serum hepatitis B surface antigen, hepatitis C virus antibodies and HIV.

    7. 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).

    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.

Sites / Locations

  • CTC, Clinical Trial Consultants ABRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cobitolimod 500mg

Arm Description

2-3 single doses of rectal cobitolimod (500mg/50ml) over 3-6 weeks

Outcomes

Primary Outcome Measures

Maximum observed plasma concentrations (Cmax)
Maximum observed plasma concentrations (Cmax)
Time to Cmax (Tmax)
Time to Cmax (Tmax)
Area under the curve from 0 to timepoint t (AUCt)
Area under the curve from 0 to timepoint t (AUCt)
AUC from 0 to infinity (AUCinf)
AUC from 0 to infinity (AUCinf)
Half-life (T1/2)
Half-life (T1/2)

Secondary Outcome Measures

Frequency, intensity and seriousness of adverse events (AEs)
Frequency, intensity and seriousness of adverse events (AEs)
Clinically significant changes in electrocardiogram (ECG), vital signs, safety laboratory
Abnormal post-dose findings assessed by the Investigator as clinically significant will be reported as AEs.
Significant changes in blood biomarkers
The difference between biomarker expression before and after treatment will be reported.

Full Information

First Posted
May 17, 2022
Last Updated
June 8, 2022
Sponsor
InDex Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05404074
Brief Title
Pharmacokinetics of Cobitolimod Enemas in Participants With Active Ulcerative Colitis
Official Title
Pharmacokinetics of Cobitolimod Enemas in Participants With Active Ulcerative Colitis
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 22, 2021 (Actual)
Primary Completion Date
October 15, 2022 (Anticipated)
Study Completion Date
October 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
InDex Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate the PK, safety and tolerability of cobitolimod ememas (500mg/50mL) given to participants with active left-sided UC.
Detailed Description
This is a single centre phase 1b study in participants with moderate to severe active UC designed to provide important supplementary data of the PK profile of cobitolimod.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ulcerative Colitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cobitolimod 500mg
Arm Type
Experimental
Arm Description
2-3 single doses of rectal cobitolimod (500mg/50ml) over 3-6 weeks
Intervention Type
Drug
Intervention Name(s)
Cobitolimod 500mg
Other Intervention Name(s)
Kappaproct
Intervention Description
Rectal administration
Primary Outcome Measure Information:
Title
Maximum observed plasma concentrations (Cmax)
Description
Maximum observed plasma concentrations (Cmax)
Time Frame
Week 6
Title
Time to Cmax (Tmax)
Description
Time to Cmax (Tmax)
Time Frame
Week 6
Title
Area under the curve from 0 to timepoint t (AUCt)
Description
Area under the curve from 0 to timepoint t (AUCt)
Time Frame
week 6
Title
AUC from 0 to infinity (AUCinf)
Description
AUC from 0 to infinity (AUCinf)
Time Frame
week 6
Title
Half-life (T1/2)
Description
Half-life (T1/2)
Time Frame
week 6
Secondary Outcome Measure Information:
Title
Frequency, intensity and seriousness of adverse events (AEs)
Description
Frequency, intensity and seriousness of adverse events (AEs)
Time Frame
week 8
Title
Clinically significant changes in electrocardiogram (ECG), vital signs, safety laboratory
Description
Abnormal post-dose findings assessed by the Investigator as clinically significant will be reported as AEs.
Time Frame
week 8
Title
Significant changes in blood biomarkers
Description
The difference between biomarker expression before and after treatment will be reported.
Time Frame
week 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and able to give written informed consent for participation in the study. Male or female participant aged ≥18 years. Established diagnosis of UC, with minimum time from diagnosis of at least 3 months before screening. Moderate to severe active left-sided UC (disease should extend 15 cm or more above the anal verge and may extend beyond the splenic flexure) 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. Clinically acceptable medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator. Women only: WOCBP must practice abstinence (only allowed when this is the preferred and usual lifestyle of the participant) 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. 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) 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, JAK-inhibitors, 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 e.g., any positive result on screening for serum hepatitis B surface antigen, hepatitis C virus antibodies and HIV. 7. 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). 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johan Levin, PM
Phone
+46 8 122 038 56
Email
johan.levin@indexpharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Karin Arnesson, CTM
Phone
+46 8 122 038 57
Email
karin.arnesson@indexpharma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Johan Levin
Organizational Affiliation
InDex Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
CTC, Clinical Trial Consultants AB
City
Uppsala
Country
Sweden
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Per Hellström, Prof

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Pharmacokinetics of Cobitolimod Enemas in Participants With Active Ulcerative Colitis

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