Clinical Trial Results:
A Phase Ib/IIa, randomized, double blind, placebo controlled, multicenter clinical trial to evaluate the safety, pharmacokinetics and efficacy of oral treatment with OST-122 in patients with moderate to severe ulcerative colitis
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Summary
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EudraCT number |
2019-004090-50 |
Trial protocol |
ES |
Global end of trial date |
27 Dec 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Jun 2026
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First version publication date |
17 Jun 2026
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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 |
CT-OST-122-02
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04353791 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Oncostellae S.L
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Sponsor organisation address |
Edificio FEUGA D5. Rúa Lope Gómez de Marzoa s/n, Santiago de Compostela, Spain, 15705
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Public contact |
Guido Kurz, Oncostellae S.L., +34 617 640 327, guido.kurz@oncostellae.com
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Scientific contact |
Guido Kurz, Oncostellae S.L., +34 617 640 327, guido.kurz@oncostellae.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 |
18 Dec 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
27 Dec 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
27 Dec 2022
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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 |
The trial primary goal will be to evaluate the safety and tolerability of OST-122 in patients with moderate to severe active ulcerative colitis disease over 28 days of trearment.
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Protection of trial subjects |
The study was conducted in compliance with the ICH Guidelines for Good Clinical Practice (GCP), the ethical principles derived from the Declaration of Helsinki, applicable local regulatory requirements, and the study protocol. All candidates taking part in the study were individually and fully informed about the nature of the study (aims, type of treatment, methodology) and the drug tested (expected risk/benefits, possible side effects) as well as their rights and responsibilities if they decided to participate. All were required to read a Patient Information Sheet and sign an Informed Consent Form (ICF).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Sep 2020
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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 |
Spain: 21
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Country: Number of subjects enrolled |
Ukraine: 16
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Worldwide total number of subjects |
37
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EEA total number of subjects |
21
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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) |
37
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||
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Pre-assignment
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Screening details |
Subjects were eligible if aged 18 to 75 years with moderate to severe ulcerative active colitis (Total Mayo score 5-10, Endoscopic score ≥2) and with inadequate/loss of response, or intolerance to conventional (steroids and immunomodulators) and/or advanced therapy (ie. anti-TNFα, anti-integrin, anti-interleukin 12/23). | |||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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OST-122 400mg | |||||||||||||||
Arm description |
Subjects received 400mg of OST-122 in a single oral daily dose for 28 days | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
OST-122
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Investigational medicinal product code |
OST-122
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Size 0 hard gelatine capsules filled with OST-122 and cellulose microcrystalline packed in blisters containing each one 200mg of OST-122.
OST-122 was administered in the morning, under fasting conditions and with 240 mL of water. Fasting conditions were kept for an additional hour and a half after medication intake.
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Arm title
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Placebo | |||||||||||||||
Arm description |
Subjects received 400mg of Placebo in a single oral daily dose for 28 days | |||||||||||||||
Arm type |
Placebo | |||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Size 0 hard gelatine capsules filled with Placebo and cellulose microcrystalline packed in blisters containing each one 200mg. It was administered in the morning, under fasting conditions and with 240 mL of water. Fasting conditions were kept for an additional hour and a half after medication intake.
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Baseline characteristics reporting groups
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Reporting group title |
OST-122 400mg
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Reporting group description |
Subjects received 400mg of OST-122 in a single oral daily dose for 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Subjects received 400mg of Placebo in a single oral daily dose for 28 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
OST-122 400mg
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Reporting group description |
Subjects received 400mg of OST-122 in a single oral daily dose for 28 days | ||
Reporting group title |
Placebo
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Reporting group description |
Subjects received 400mg of Placebo in a single oral daily dose for 28 days | ||
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End point title |
Safety and tolerability of OST-122 [1] | |||||||||||||||||||||||||||||||||
End point description |
Safety evaluations included the incidence, severity, and relationship of adverse events (AEs), as well as clinically significant changes in vital signs, physical examination findings, laboratory parameters, and electrocardiograms (ECGs).
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End point type |
Primary
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End point timeframe |
Safety and tolerability of OST-122 was assessed from baseline to Day 43 (end of follow-up)
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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: The number of subjects with at least one adverse event was summarised by proportion and 95% confidence interval using exact methods based on the binomial Clopper-Pearson method, independently of treatment groups and by type of AE. Comparison between treatment groups in the number (%) of subjects reporting one or more treatment-emergent AEs by preferred term was performed using Fisher's exact test. |
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| No statistical analyses for this end point | ||||||||||||||||||||||||||||||||||
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End point title |
Percentage of participants achieving clinical response at Day 28 | ||||||||||||
End point description |
Clinical Response is defined as an improvement in the Total Mayo Score by ≥ 3 points and a decrease of 30% versus baseline, plus a decrease in rectal bleeding by ≥ 1 points and an absolute rectal bleeding score of 0 or 1.
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End point type |
Secondary
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants achieving clinical remission at Day 28 | ||||||||||||
End point description |
Clinical remission is defined as a Total Mayo Score ≤ 2 and no individual subscore >1 plus a rectal bleeding score of 0
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End point type |
Secondary
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants with an improvement of the Mayo rectal bleeding subscore by ≥1 point at Day 28 | ||||||||||||
End point description |
The rectal bleeding score is one of the four subscores of the total Mayo score and assesses the severity of rectal bleeding. It is measured on a scale from 0 to 3, where 0 = no blood seen; 1 = streaks of blood with stool less than half the time; 2 = obvious blood with stool most of the time; and 3 = blood alone passed
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End point type |
Secondary
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants with an improvement of the Mayo stool frequency subscore by ≥ 1 point al Day 28 | ||||||||||||
End point description |
The stool frequency score is one of the four subscores of the total Mayo score and assesses the increase in stool frequency relative to normal. It is measured on a scale from 0 to 3, where 0 = normal number of stools; 1 = 1–2 stools more than normal; 2 = 3–4 stools more than normal; and 3 = ≥5 stools more than normal.
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End point type |
Secondary
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants with improvement of PRO-2 by ≥2 points | ||||||||||||
End point description |
The PRO-2 is a patient-reported outcome derived from the stool frequency score and rectal bleeding score components of the total Mayo score and is defined as the sum of these two subscores.
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End point type |
Secondary
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants with an improvement of the Mayo endoscopic subscore by ≥1 point at Day 28 | ||||||||||||
End point description |
The endoscopic subscore is one of the four subscores of the total Mayo score and assesses mucosal appearance on endoscopy. It is measured on a scale from 0 to 3, where 0 = normal or inactive disease; 1 = mild disease (erythema, decreased vascular pattern, mild friability); 2 = moderate disease (marked erythema, absent vascular pattern, friability, erosions); and 3 = severe disease (spontaneous bleeding, ulceration).
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End point type |
Secondary
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Pharmacokinetics [2] | ||||||||||||||||||||||||
End point description |
The following pharmacokinetic parameters were calculated on Day 1 and Day 28 (endo of treatment, EoT):
Cmax: Maximum observed plasma concentration, obtained directly from the data – without interpolation.
Area under the curve (AUC): Cumulative area under the plasma concentration time curve calculated from 0 to the last observed concentration above the Lower Limit Of Quantification (LLOQ), using the mixed model linear log trapezoidal rule.
Tmax: Time of maximum observed plasma concentration; obtained directly from the data, without interpolation. If it occurs at more than one time point, Tmax was defined as the first time point with this value.
Ctrough: concentration reached by a drug immediately before the next dose is administered.
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End point type |
Other pre-specified
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End point timeframe |
Blood samples for parent compound determination were collected at baseline [pre-dose], [+ 10 min], [+ 20 min], [+ 40 min], [+ 60 min], [+ 1.5h], [+ 2 h], [+ 2.5 h], [+ 3h], [+ 4h], and [+ 6h], post-medication on Days 1 and 28 (End of treatment).
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| Notes [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Justification: Placebo arms do not have parental compound, therefore descriptive statistics are not applicable. |
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| No statistical analyses for this end point | |||||||||||||||||||||||||
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End point title |
Percentage of participants achieving histological response at Day 28 | ||||||||||||
End point description |
Histological response is defined as a Robarts Histopathology Index ≤ 9 at Day 28 and baseline RHI > 9, with subscores of 0 for neutrophils in epithelium and without ulcers or erosions (in R1 or R2 location).
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End point type |
Post-hoc
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End point timeframe |
Day 28
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of participants achieving histological remission at Day 28 | ||||||||||||
End point description |
Defined as the percentage of subjects with Robarts Histopathological Index (RHI) ≤ 3 at Day 28 and baseline RHI > 3, with subscores of 0 for neutrophils in lamina propria and epithelium and without ulcers or erosions (in region R1 or R2).
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End point type |
Post-hoc
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End point timeframe |
Day 28
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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 |
Adverse events (AEs) were collected from the time when the subject signed the consent form until the last final follow-up visit (or at the time of early discontinuation of the subject from the study)
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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 |
25.1
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Reporting groups
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Reporting group title |
OST-122 400mg
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Reporting group description |
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Reporting group title |
Placebo
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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08 Jan 2021 |
Due to the COVID-19 pandemic, mitigation measures were implemented including the replacement of selected on-site visits with telephone contacts to minimise patient travel while ensuring adequate monitoring.
Additionally, inclusion of patients with inadequate response or intolerance to Ustekinumab, Tofacitinib or other JAK inhibitors was allowed, subject to a 60-day washout period. |
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19 Aug 2021 |
The number of participants in the 400 mg cohort was increased while maintaining the overall sample size, with removal of the 800 mg cohort. This adjustment strengthens the robustness and interpretability of results and supports the assessment of safety, tolerability, pharmacokinetics and preliminary efficacy in line with the exploratory nature of this proof-of-concept study. |
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23 Dec 2021 |
The washout period for prior medications was reduced to allow patients with moderate to severe active ulcerative colitis, inadequately controlled with current therapy, to access IMP as early as possible. This is particularly relevant given that OST-122 is a selective JAK3/TYK2 inhibitor designed to act exclusively at the gastrointestinal tract level, with limited oral absorption and rapid hepatic metabolism. This pharmacokinetic profile makes a prolonged washout period unnecessary from a safety perspective. |
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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 | |||
