Clinical Trials Register

Summary
EudraCT Number:	2022-000942-14
Sponsor's Protocol Code Number:	0243CT01
National Competent Authority:	Romania - National Agency for Medicines and Medical Devices
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2024-11-28
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Romania - National Agency for Medicines and Medical Devices

A.2

EudraCT number

2022-000942-14

A.3

Full title of the trial

A Phase IIa, randomized, double-blind, placebo-controlled, multicentre study of a once daily multiple oral administration of KSP-0243 in patients with mild-to-moderate ulcerative colitis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase IIa, randomized, double-blind, placebo-controlled, multicentre study of a once daily multiple oral administration of KSP-0243 in patients with mild-to-moderate ulcerative colitis

A.4.1

Sponsor's protocol code number

0243CT01

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Kissei Pharmaceutical Co., Ltd.
B.1.3.4	Country	Japan
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Kissei Pharmaceutical Co., Ltd.
B.4.2	Country	Japan
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Kissei Pharmaceutical Co., Ltd.
B.5.2	Functional name of contact point	Clinical Project Management
B.5.3	Address:
B.5.3.1	Street Address	3-1-3 Koishikawa, Bunkyo-ku
B.5.3.2	Town/ city	Tokyo
B.5.3.3	Post code	112-0002
B.5.3.4	Country	Japan
B.5.4	Telephone number	+81(0)3-5684-3576
B.5.5	Fax number	+81(0)3-5804-8560
B.5.6	E-mail	rinsyousiken@pharm.kissei.co.jp

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	KSP-0243
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not Applicable
D.3.9.3	Other descriptive name	KSP-0243
D.3.9.4	EV Substance Code	SUB274548
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ulcerative colitis

E.1.1.1

Medical condition in easily understood language

Ulcerative colitis

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

- To assess the safety and tolerability of a once-daily multiple oral administration of KSP-0243 in patients with UC;
- To characterise the pharmacokinetic (PK) of a once-daily multiple oral administration of KSP-0243 in patients with UC.

E.2.2

Secondary objectives of the trial

-To assess the pharmacodynamic (PD) response in faecal calprotectin (fCP) and C-reactive protein (CRP) following a once-daily multiple oral administration of KSP-0243 in patients with UC
-To evaluate changes in clinical activity following a once-daily multiple oral administration of KSP-0243 in patients with UC.
-Change from baseline in HIF-1α positive cell count on Day 28
-Change from baseline in gene expression profiling (RNA-seq) on Day 28
-Change from baseline in mucosal barrier-related proteins, ie, claudin-1 (CLDN1), mucin 3 (MUC3), β-defensin 1 (DEFB1), and trefoil factor 3 (TFF3) levels, on Day 28
-Change from baseline in serum leucine-rich alpha 2 glycoprotein (LRG) level on Days 7, 14, 21, 28 (EOT), and 56 (EOS)
-Change from baseline in prostaglandin E-major urinary metabolite (PGE-MUM) level on Days 7, 14, 21, 28 (EOT), and 56 (EOS)

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Male and female outpatients aged 18 to 74 years (inclusive) at the time of informed consent form (ICF) signature.
2.Patients with body mass index between 18 and 35 kg/m2(inclusive).
3.Diagnosis of UC at least 3 months prior to first dose of the study drug on Day 1.
4.Active mild-to-moderate UC defined at screening by the following criteria:
a. Endoscopic appearance typical for UC and extending >15 cm from anal verge
b. Mayo Score ≥3 and ≤10
c. mMES ≥1
d. Mayo rectal bleeding (RB) subscore (RBS) ≥1.
5.Evidence of active inflammation at screening by RHI ≥4 with neutrophils in the epithelium (subscore ≥1) in sigmoid or rectum.
6.Currently receiving treatment for UC with oral 5-aminosalicylic acid (eg, mesalamine, sulfasalazine) and/or corticosteroids (prednisone [≤20 mg/day] or equivalent, budesonide or budesonide multi-matrix [≤9 mg/day]) on a stable dose for at least 4 weeks prior to first screening visit, or with azathioprine (≤3 mg/kg/day) or 6-mercaptopurine (≤2 mg/kg/day) on a stable dose for at least 12 weeks prior to first screening visit.
7.Patients who demonstrated an inadequate response or loss of response to current treatment for UC.
8.Patients who agree to abstain from heterosexual activity, use adequate hormonal contraception, or use highly effective double barrier contraception (ie, a combination of condom or diaphragm AND hormonal contraception associated with inhibition of ovulation, intrauterine device, or intrauterine hormone-releasing system) during the study and for 12 weeks after the last dose of study drug, unless:
a. Patient is a female of non-childbearing potential, defined as women who had surgical sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) at least 90 days prior to first screening visit OR postmenopausal women ≥45 years of age with > 1 year since last menstrual period.
b. Patient is a surgically sterilized male through vasectomy or bilateral orchiectomy at least 90 days prior to first screening visit.
9.For women of childbearing potential, a negative serum pregnancy test at first screening visit and a negative urine pregnancy test within 24 hours prior to first dose of the study drug.
10.Patients who understand the study procedures and agree to participate in the study by giving informed consent.

E.4

Principal exclusion criteria

1. Any concurrent clinically significant, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, haematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator might confound study results or pose additional risk to the patient by their participation in the study.
2. Any abnormal finding in physical examination, vital signs, 12-lead ECG, or laboratory assessment at first screening visit considered as clinically significant and that in the opinion of the investigator might pose additional risk to the patient by their participation in the study.
3. Diagnosis of Crohn’s disease, indeterminate colitis, pouchitis, ischemic colitis, microscopic colitis, radiation colitis, diverticular-disease associated colitis, stenosis of the intestine, colostomy, ileostomy, abscesses or toxic megacolon, malabsorption, short bowel syndrome, history of colorectal cancer, colorectal dysplasia (with the exception of dysplasia in polyps which have been removed), extensive mucosal shedding, deep-seated ulcers, or recent colectomy.
4. Concurrent malignancy or prior malignancy within 2 years with the exception of adequately treated nonmelanoma skin cancer, adequately treated cervical cancer, or superficial bladder cancer.
5. Diagnosis or suspected liver function impairment (aspartate aminotransferase or alanine aminotransferase >3 × upper limit of normal).
6. Current bacterial or parasitic pathogenic enteric infection, including treatment for Clostridium difficile infection or other pathogens within 30 days prior to randomization.
7. History of chronic infections, including but not limited to tuberculosis (TB), human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) within 6 months prior to first screening visit.
8. Positive immunological test at screening for TB (QuantiFERON®-TB Gold test), HIV, HCV, and HBV, or positive serological test for syphilis.
9. Any live vaccinations within 30 days prior to first screening visit.
10. Current or recent history of alcohol dependence or illicit drug use.
11. Pregnant or lactating females.
12. Prior use of epoetin alfa.
13. Use of monoclonal antibodies (e.g., infliximab, golimumab, adalimumab, vedolizumab, ustekinumab, natalizumab, certolizumab) for the treatment of UC within 6 months prior to first screening visit.
14. Use of tofacitinib, oral cyclosporine, tacrolimus, mycophenolate mofetil, or methotrexate within 4 weeks prior to first screening visit.
15. Use of dihydroorotate dehydrogenase inhibitors leflunomide/teriflunomide within 6 months prior to first screening visit.
16. Use of OATP1B1/OATP1B3 substrates, OATP1B1/OATP1B3 inhibitors, and OAT3 inhibitors within 2 weeks or 5 × respective half-life (whichever is longer) prior to first screening visit.
17. Use of other investigational product within 8 weeks or 5 × the respective half-life (whichever is longer) prior to first screening visit and during the entire study.
18. Use of oral corticosteroids >20 mg/day, intravenous corticosteroids, or rectal and topical corticosteroids/aminosalicylates within 4 weeks prior to first screening visit.
19. Unable to attend study visits or comply with procedures.
20. Concurrent participation in any other interventional study.

E.5 End points

E.5.1

Primary end point(s)

The primary safety endpoints are:
• incidence and severity of adverse events (AEs)/treatment-emergent AEs (TEAEs)
• incidence and severity of adverse drug reactions (ADRs)
• clinical laboratory assessments (haematology, biochemistry, urinalysis, and
hematopoietic and coagulation markers)
• 12-lead ECG
• vital signs
• physical examinations.

E.5.1.1

Timepoint(s) of evaluation of this end point

•For the primary endpoint: incidence and severity of adverse events (AEs)/treatment-emergent AEs (TEAEs), the timepoint is from the time ICF is signed until follow-up (EOS) visit.
•For the primary endpoint: incidence and severity of adverse drug reactions (ADRs, the timepoint is from the first treatment administration until follow-up (EOS) visit.
•For the primary endpoints: clinical laboratory assessments, 12-lead ECG, vital signs, physical examinations, the timepoint is up to week 8(EOS) (Day 56± 3 days).

E.5.2

Secondary end point(s)

• Proportion of patients achieving clinical response on Day 28 (defined as a reduction in Mayo Score of ≥3 points and ≥30% from baseline with either RBS of 0 or 1 or a
reduction in RBS of ≥1 among patients with baseline RBS >0 and baseline mMES
sigmoid >0)
• Proportion of patients achieving clinical remission on Day 28 (defined as a Mayo Score of ≤2 with no individual subscore >1 among patients with baseline mMES sigmoid >0)
• Proportion of patients achieving endoscopic improvement on Day 28 (defined as a
mMES of 0 or 1 among patients with a baseline mMES >1)
• Proportion of patients with improvement in RBS on Day 28 (defined as a decrease in RBS ≥1 among patients with baseline RBS >0)
• Proportion of patients with resolution of RB on Day 28 (defined as RBS =0 among
patients with baseline RBS >0). Proportion of patients achieving histologic response on Day 28 (defined as a decrease from baseline in RHI ≥7 among patients with a baseline RHI ≥7)
• Proportion of patients achieving histologic remission on Day 28 (defined as RHI ≤3
with lamina propria neutrophils subscore =0 and neutrophils in epithelium subscore =0 among patients with both baseline subscores >0)
• Proportion of patients achieving mucosal healing on Day 28 (defined as histologic
remission + endoscopic improvement)
• Proportion of patients achieving minimum histologic disease activity on Day 28
(defined as RHI <5 among patients with baseline RHI ≥5)
• Proportion of patients achieving histologic healing on Day 28 (defined as Geboes
Histopathology Score [GHS] ≤2 among patients with baseline GHS >2).

E.5.2.1

Timepoint(s) of evaluation of this end point

For the secondary end points, timepoint of evaluation is up to 28 days.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Moldova, Republic of

Georgia

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The overall study ends when the last participant completes the last study-related contact, withdraws consent, or is lost to follow-up (ie, the participant is unable to be contacted by the investigator).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

Information not present in EudraCT

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

NONE

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-09-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-10-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-11-20

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