Clinical Trial Results:
Pharmacokinetics of Cobitolimod Enemas in Participants with active Ulcerative Colitis
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Summary
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EudraCT number |
2021-003023-14 |
Trial protocol |
SE |
Global end of trial date |
19 Jan 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
22 Nov 2023
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First version publication date |
22 Nov 2023
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CSUC-02/21
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05404074 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
InDex Pharmaceuticals AB
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Sponsor organisation address |
Berzelius väg 13, Solna, Sweden, 171 65
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Public contact |
Eva Arlander, Chief Development Officer, InDex Pharmaceuticals AB, +46 (0)8 122 038 70, eva.arlander@indexpharma.com
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Scientific contact |
Eva Arlander, Chief Development Officer, InDex Pharmaceuticals AB, +46 (0)8 122 038 70, eva.arlander@indexpharma.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
19 Jan 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Jan 2023
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Jan 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess PK properties of cobitolimod in plasma after administration of cobitolimod enema in participants with active UC and in remission.
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Protection of trial subjects |
The study was conducted in accordance with ethical principles that have their origin in the Declaration of Helsinki and are compliant with the International Conference of Harmonisation (ICH) Good Clinical Practice (GCP) E6 (R2) guidance, the European Union (EU) Clinical Trials Directive 2001/20/EC, and applicable local regulatory requirements.
It was the responsibility of the Investigator or an authorised associate to give each potential study participant adequate verbal and written information before any study specific assessments were performed.
The information included the objectives and the procedures of the study as well as any risks or inconvenience involved. It was emphasised that participation in the study was voluntary, and that the participant could withdraw from participation at any time and for any reason, without any prejudice. All participants were given the opportunity to ask questions about the study and were given sufficient time to consider participation before signing the Informed consent form (ICF).
Before performing any study-related procedures, the ICF was signed and personally dated by the participant and by the Investigator. A copy of the participant information including the signed ICF was provided to the participant.
Documentation of the discussion and the date of informed consent were recorded in the source documentation and in the electronic case report form (eCRF). The participant information sheet and the signed ICF were filed by the Investigator for possible future audits and/or inspections.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Nov 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Sweden: 8
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Worldwide total number of subjects |
8
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EEA total number of subjects |
8
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
7
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From 65 to 84 years |
1
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85 years and over |
0
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Recruitment
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Recruitment details |
The participants were identified by referring participating physicians or recruited from advertising in media (including social media) or recruited from the CTC’s database of study participants and from the Uppsala University Hospital catchment area. | ||||||
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Pre-assignment
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Screening details |
In total, 12 participants were screened, and 8 participants were included and dosed in the study (Full analysis set). Seven (7) participants completed the study according to protocol (PK analysis set) and of those, 4 participants were in clinical remission after the second dose and therefore received a third dose cobitolimod. | ||||||
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Period 1
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Period 1 title |
Overall period
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Total | ||||||
Arm description |
All 8 participants included and dosed in the study. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Cobitolimod 500 mg
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Investigational medicinal product code |
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Other name |
Kappaproct
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Pharmaceutical forms |
Rectal solution
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Routes of administration |
Rectal use
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Dosage and administration details |
Rectal administration. Participants self-administered a single rectal enema at Visit 2, 3 and, if the participants were in remission, at Visit 4.
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Baseline characteristics reporting groups
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Reporting group title |
Total
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Reporting group description |
All 8 participants included and dosed in the study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Remitters
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This analysis set summarizes data for participants in remission (remitters).
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Subject analysis set title |
Non-remitters
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Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
This analysis set summarizes data for participants not in remission (non-remitters)
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End points reporting groups
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Reporting group title |
Total
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Reporting group description |
All 8 participants included and dosed in the study. | ||
Subject analysis set title |
Remitters
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
This analysis set summarizes data for participants in remission (remitters).
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Subject analysis set title |
Non-remitters
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
This analysis set summarizes data for participants not in remission (non-remitters)
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End point title |
Maximum Observed Plasma Concentrations (Cmax) [1] | ||||||||||||||||||
End point description |
Venous blood samples (approximately 5 mL) for the determination of plasma concentrations of cobitolimod after administration of the study intervention, were collected through an indwelling venous catheter.
At Visit 4b, only the remitters were included.
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End point type |
Primary
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End point timeframe |
Week 0 (Visit 2) and Week 6 (Visit 4b, remitters only)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, the end-point is reported using descriptive statistics only. |
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| Notes [2] - PK analysis set. [3] - PK analysis set. Visit 4b = 0 subjects |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Time to Cmax (Tmax) [4] | ||||||||||||||||||
End point description |
Measure Description Venous blood samples (approximately 5 mL) for the determination of plasma concentrations of cobitolimod after administration of the study intervention, were collected through an indwelling venous catheter.
At Visit 4b (Week 6), only the remitters were included.
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End point type |
Primary
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End point timeframe |
Week 0 (Visit 2) and Week 6 (Visit 4b, remitters only)
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| Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, the end-point is reported using descriptive statistics only. |
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| Notes [5] - PK analysis set. [6] - PK analysis set. Visit 4b = 0 subjects |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Area Under the Curve From 0 to Timepoint of the Last Detectable Plasma Concentration (AUC0-last) [7] | ||||||||||||||||||
End point description |
Venous blood samples (approximately 5 mL) for the determination of plasma concentrations of cobitolimod after administration of the study intervention, were collected through an indwelling venous catheter.
At Visit 4b, only the remitters were included.
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End point type |
Primary
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End point timeframe |
Week 0 (Visit 2) and Week 6 (Visit 4b, remitters only)
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| Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, the end-point is reported using descriptive statistics only. |
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| Notes [8] - PK analysis set. [9] - PK analysis set. Visit 4b = 0 subjects |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
AUC From 0 to Infinity (AUCinf) [10] | ||||||||||||||||||
End point description |
Venous blood samples (approximately 5 mL) for the determination of plasma concentrations of cobitolimod after administration of the study intervention, were collected through an indwelling venous catheter.
At Visit 2, the terminal elimination constant (lambdaz) could not be calculated for 6 out of 7 participants and subsequentially the lambdaz dependent PK parameter AUCinf could not be calculated. In the single participant (Non-remitter) where lambdaz could be calculated, the AUCinf was 26.4 h*nmol/L.
At Visit 4b, only the remitters were included.
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End point type |
Primary
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End point timeframe |
Week 0 (Visit 2) and Week 6 (Visit 4b, remitters only)
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| Notes [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, the end-point is reported using descriptive statistics only. |
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| Notes [11] - PK analysis set. Visit 4b = 3 subjects [12] - PK analysis set. Visit 4b = 0 subjects |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Half-life (T1/2) [13] | ||||||||||||||||||
End point description |
Venous blood samples (approximately 5 mL) for the determination of plasma concentrations of cobitolimod after administration of the study intervention, were collected through an indwelling venous catheter.
At Visit 2, the terminal elimination constant (lambdaz) could not be calculated for 6 out of 7 participants and subsequentially the lambdaz dependent PK parameter T1/2 could not be calculated. In the single participant (Non-remitter) where lambdaz could be calculated, the plasma T1/2 was estimated to be 0.747 hours.
At Visit 4b, only the remitters were included.
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End point type |
Primary
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End point timeframe |
Week 0 (Visit 2) and Week 6 (Visit 4b, remitters only)
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| Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Per protocol, the end-point is reported using descriptive statistics only. |
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| Notes [14] - PK analysis set. Visit 4b = 3 subjects [15] - PK analysis set. Visit 4b = 0 subjects |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Frequency, Intensity and Seriousness of Adverse Events (AEs) | ||||||||||||||||||||||||||||||||||||||||||
End point description |
AEs (including serious AEs [SAEs]) were collected from the start of study intervention administration until the end-of-study visit. The grading of the severity/intensity (grade 1 to grade 5) of AEs followed the common terminology criteria for AEs (CTCAE) v5.0. AEs were assessed as unlikely, possibly or probably related to the study intervention.
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End point type |
Secondary
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End point timeframe |
From the start of study intervention administration until the end-of-study visit.
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| Notes [16] - Full analysis set. [17] - Full analysis set. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||
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End point title |
Clinically Significant Changes in Electrocardiogram (ECG) | |||||||||
End point description |
Single 12-lead ECG was recorded in supine position after 10 minutes of rest using an ECG machine. Heart rate (HR) and PR, QRS, QT and QTcF intervals were recorded. Safety ECGs were reviewed and interpreted on-site by the Investigator.
Any abnormalities were specified and documented as clinically significant or not clinically significant. Abnormal post-dose findings assessed by the Investigator as clinically significant were reported as AEs.
There were no clinically significant trends in the overall ECG interpretations, no clinically significant change from baseline in ECG parameters and no clinically significant patterns in ECG associated with cobitolimod.
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End point type |
Secondary
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End point timeframe |
At pre-defined time points from screening (Visit 1a) to End-of-study (Visit 5, Week 8)
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| Notes [18] - Full analysis set. [19] - Full analysis set. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Clinically Significant Changes in Vital Sign | |||||||||
End point description |
Systolic and diastolic blood pressure and pulse were measured in supine position after 10 minutes of rest.
Any vital signs outside the normal ranges were judged as not clinically significant (NCS) or clinically significant (CS). The assessment was recorded in the eCRF. Post-study intervention vital signs judged as “abnormal, clinically significant” by the Investigator were reported as AEs.
There were no clinically significant changes from baseline in mean vital signs over time and no clinically significant vital signs patterns associated with cobitolimod
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End point type |
Secondary
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End point timeframe |
At pre-defined time points from screening (Visit 1a) to End-of-study (Visit 5, Week 8)
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| Notes [20] - Full analysis set. [21] - Full analysis set. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Clinically Significant Changes in Safety Laboratory Parameters | |||||||||
End point description |
Blood samples for analysis of clinical chemistry and haematology parameters were collected through venepuncture/an indwelling venous catheter and analysed by routine analytical methods. Faeces was analysed for gastrointestinal infections prior to enrolment. Calprotectin in faeces was analysed from stool samples that the participant brought to the clinic at Visits 2 and 4. Lab values outside the normal ranges were judged as not clinically significant or clinically significant.
There were no safety laboratory measurement values (including clinical chemistry and haematology) that were assessed as abnormal clinically significant. Individual abnormal laboratory values assessed as not clinically significant were noted. There were some trends in changes in mean laboratory parameters from baseline (Visit 1a) to end-of-study (Visit 4b, Day 42) and some minor differences in change between remitters and non-remitters for some parameters. The changes were assessed as not clinically significant.
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End point type |
Secondary
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End point timeframe |
At pre-defined time points from screening (Visit 1a) to End-of-study (Visit 5, Week 8)
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| Notes [22] - Full analysis set. [23] - Full analysis set. |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Clinically Significant Changes in Physical Examinations | |||||||||
End point description |
A complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. Any abnormalities were specified and documented as clinically significant or not clinically significant. Abnormal post-dose findings assessed by the Investigator as clinically significant were reported as AEs.
In general, no clinically significant abnormalities were observed during any physical examination. Occasional abnormal observations were assessed as not clinically significant.
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End point type |
Secondary
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End point timeframe |
At pre-defined time points from screening (Visit 1a) to End-of-study (Visit 5, Week 8)
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| Notes [24] - Full analysis set. [25] - Full analysis set. |
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| No statistical analyses for this end point | ||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
AEs (including serious AEs [SAEs]) were collected from the start of study intervention administration until the end-of-study visit.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.1
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Reporting groups
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Reporting group title |
Remitters
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Reporting group description |
This group summarizes data for participants in remission (remitters). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Non-remitters
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Reporting group description |
This group summarizes data for participants not in remission (non-remitters) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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20 Dec 2021 |
Change to include participants with active ulcerative colitis instead of participants with active left-sided ulcerative colitis. Change to include participants who had previously been exposed to cobitolimod. Increased time window for conduct of Visit 4. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
