Clinical Trials Register

Summary
EudraCT Number:	2021-001940-86
Sponsor's Protocol Code Number:	RSJ10135
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2021-08-09
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2021-001940-86

A.3

Full title of the trial

A Phase 3 Study to Evaluate the Efficacy and Long-term Safety of SHR0302 for Induction, Maintenance Therapy in Subjects with Moderately to Severely Active Ulcerative Colitis

A.3.1

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

A phase 3 Study to Evaluate the Efficacy and Safety of SHR0302 in Ulcerative Colitis.

A.4.1

Sponsor's protocol code number

RSJ10135

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	Reistone Biopharma Company Limited
B.1.3.4	Country	China
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	Reistone Biopharma Company Limited
B.4.2	Country	China
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Reistone Biopharma Company Limited
B.5.2	Functional name of contact point	Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	298 Xiangke Road, 2/F, Room 201,203, Zhangjiang Hi-Tech Park,
B.5.3.2	Town/ city	Pudong, Shanghai
B.5.3.3	Post code	201210
B.5.3.4	Country	China
B.5.4	Telephone number	0086 0 21 6881 5767
B.5.5	Fax number	00 86 021 6881 3055
B.5.6	E-mail	haifeng.cao@reistonebio.com

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.3.1	Product name	SHR0302 tablets
D.3.2	Product code	SHR0302
D.3.4	Pharmaceutical form	Film-coated 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	SHR0302
D.3.9.1	CAS number	1639419-51-4
D.3.9.4	EV Substance Code	SUB196516
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	4
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	Film-coated 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

Moderately to severely active Ulcerative Colitis (UC)

E.1.1.1

Medical condition in easily understood language

Ulcerative Colitis (UC)

E.1.1.2

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10045365
E.1.2	Term	Ulcerative colitis
E.1.2	System Organ Class	100000004856

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part 1 Induction phase: to evaluate the efficacy of SHR0302 8 mg QD, compared to placebo in inducing clinical remission in adult subjects with moderately to severely active ulcerative colitis at week 8.
Part 2 Maintenance phase: to evaluate the efficacy of SHR0302 4 mg QD compared to placebo as maintenance treatment in maintaining clinical remission in adult subjects with moderately to severely active ulcerative colitis at week 52.
Part 3 Open-Label Extension phase: to evaluate the long-term safety of SHR0302 4 mg QD in adult subjects with moderately to severely active ulcerative colitis

E.2.2

Secondary objectives of the trial

Part 1
To evaluate the efficacy of SHR0302 in achieving endoscopic remission in subjects with moderately to severely active ulcerative colitis (UC).
To evaluate the efficacy of SHR0302 as induction therapy on clinical response in subjects with moderately to severely active UC.
To characterize the PK of SHR0302 in moderately to severely active UC and explore the correlation of exposure-response.
To evaluate the safety and tolerability of SHR0302 in subjects with moderately to severely active UC.
Part 2
To evaluate the efficacy of SHR0302 in endoscopic remission in subjects with moderately to severely active UC.
To evaluate the efficacy of SHR0302 as maintenance therapy on clinical response in subjects with moderately to severely active UC.
To evaluate the safety and tolerability of SHR0302 in subjects with moderately to severely active UC.
Part 3
To evaluate the efficacy of SHR0302 in Partial Mayo score remission in subjects with moderately to severely active UC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion Criteria for Part 1 Induction phase
1. Male and female subjects age ≥18 and ≤75 years of age at baseline.
2. Subject has active ulcerative colitis with a 9-point modified Mayo score of ≥5, with an endoscopic subscore of ≥2 (confirmed by central read) prior to 14 days of baseline visit. (Note: endoscopy should be performed within 14 days prior to baseline visit).
3. Subject has at least a three-month history of ulcerative colitis diagnosis at baseline.
4. Subject is deemed by the investigator as having an inadequate response, loss of response or intolerance (see appendix 5) to at least one conventional treatment (oral 5-ASA, immunosuppressants or corticosteroids), or was previously exposed to anti-TNF therapy (e.g. infliximab, adalimumab), or other biological treatment (e.g., vedolizumab) having discontinued the treatment for:
- Infliximab: a minimum of 8 weeks prior to baseline.
- Adalimumab: a minimum of 10 weeks prior to baseline.
- Ustekinumab: a minimum of 14 weeks prior to baseline.
- Vedolizumab: a minimum of 17 weeks prior to baseline.
For other biological treatments, subject should have discontinued for a minimum of 5 half-lives prior to baseline.
5. If subject is currently receiving the following “background” treatment for UC, they are eligible for the study, provided they are on a stable dose for the required period:
- Oral 5 ASA or sulfasalazine, stable dose for at least 2 weeks prior to baseline and during the study treatment period.
AND/OR
- Oral corticosteroids (prednisolone≤30mg/day or less or equivalent) stable dose for at least 2 weeks prior to baseline. This is not applicable to the subjects who have only been exposed to 5-ASA previously as per inclusion criteria 4 (e.g., subjects who have only been exposed to 5-ASA previously, to initiate an oral corticosteroid before baseline is not permitted).
6. All women of childbearing potential and all men must be willing to use at least one highly effective method of contraception from signing of informed consent, throughout the duration of the study, and for 1 month after last dose of study medication: (refer to Section 4.3 for further details on contraception requirements for this study)
- Male subjects who have a female partner of childbearing potential must be willing to use condom in addition to a highly effective contraceptive method.
7. Subject is willing and able to comply with the scheduled visits and treatment plan, laboratory testing and other study procedures.
8. Subject is capable of providing a signed and dated informed consent form indicating the subject has been informed of all pertinent aspects of the study.
Inclusion Criteria for Part 2 Maintenance phase
1. Subject has completed part 1 induction phase and achieved clinical response at week 8.
2. Women of childbearing potential must have negative urine pregnancy test prior to starting Part 2 Maintenance phase.
Inclusion Criteria for Part 3 Open-Label Extension phase
1. Subject has completed the 8-week induction treatment phase and was classified as not meeting clinical response criteria. Or
Subject has discontinued treatment early in the maintenance phase due to disease worsening per protocol definition stated in Appendix 1. Or
Subject has completed the maintenance phase.
2. Women of childbearing potential must have a negative urine pregnancy test prior to starting Part 3 Open-Label Extension phase.

E.4

Principal exclusion criteria

Exclusion criteria for Part 1 Induction phase
1. Subject has a diagnosis of indeterminate colitis, or clinical findings suggestive of Crohn’s disease.
2. Subject with ulcerative colitis, which is confined to a proctitis (distal 15 cm or less).
3. Treatment naïve subject diagnosed with ulcerative colitis.
4. Subject is displaying clinical signs of ischemic colitis, fulminant colitis or toxic megacolon.
5. Subject had previous surgery as a treatment for ulcerative colitis or likely to require surgery during the study period.
6. Subject has evidence of pathogenic bowel infection. Subjects had Clostridium difficile or other intestinal infection within 30 days of screening endoscopy or test positive at screening for C. difficile toxin or other intestinal pathogens.
7. Subject currently has or had a history of active tuberculosis (TB) or latent TB infection, defined as:
- A positive Mantoux Purified Protein Derivative (PPD) skin test result (> 5 mm of induration), or positive QuantiFERON TB Gold (QFT Gold test), or T-Spot test.
8. Subject is receiving any of the following therapies:
- Azathioprine/6-mercaptopurine, methotrexate, thalidomide within 7 days prior to baseline.
- Cyclosporine, mycophenolate, tacrolimus within 4 weeks prior to baseline.
- Interferon therapy within 8 weeks prior to baseline.
- Intravenous corticosteroids or rectally administered formulation of corticosteroids or 5-ASA within 2 weeks prior to baseline.
9. Subject had any prior treatment with lymphocyte-depleting agents/therapies. Subjects who have received rituximab or other selective B lymphocyte depleting agents are eligible if they have not received such therapy for at least 1 year prior to baseline.
10. Subject has previously received JAK inhibitors, such as tofacitinib, baricitinib, upadacitinib, filgotinib.
11. Subject with evidence of clinically relevant abnormalities which may affect subject safety or interpretation of study results at screening:
Hemoglobin levels < 8.0 g/dL or hematocrit < 30%
An absolute white blood cell (WBC) count of < 3.0 × 109 /L (<3000/mm3) or absolute neutrophil count (ANC) of < 1.2 × 109 /L (<1200/mm3).
Thrombocytopenia, as defined by a platelet count < 100 × 109 /L (<100,000/mm3).
Total bilirubin, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2×ULN.
eGFR ≤ 50 ml/min based on Cockcroft-Gault calculation, or is currently undergoing regular hematodialysis.
12. Subject has a screening 12-lead ECG that demonstrates clinically relevant abnormalities which may affect subject safety if being enrolled into the study or interpretation of study results.
13. Subject currently has or had:
a clinically significant infection within 1 month of baseline
a history of more than one episode of herpes zoster or disseminated zoster (single episode).
any infection otherwise deemed by the investigator to have the potential for exacerbation by participation in the study.
any infection requiring antimicrobial therapy within 2 weeks of screening.
14. Subject has current immunization with any live virus vaccine or history of immunization with any live virus vaccine within 8 weeks of baseline.
15. Subject with a first-degree relative with a hereditary immunodeficiency.
16. Subject with a history of any lymphoproliferative disorder, history of lymphoma, leukemia, multiple myeloma, or signs and symptoms that are suggestive of current lymphatic disease.
17. Subject has any condition possibly affecting oral drug absorption.
18. Women who are pregnant or lactating, or planning pregnancy while enrolled in the study.
19. Subject who has a history of alcohol or drug abuse
20. Subject infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses.
21. Subject is receiving or expected to receive prohibited concomitant medication(s).
Exclusion criteria for Part 2 Maintenance phase
1. Subject with any clinically significant condition at the end of 8-week induction treatment from Part 1 Induction phase, that in the opinion of investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis.
2. Subject who, in the opinion of the investigator or sponsor, is unlikely to be cooperative or able to comply with study procedures, or any other condition which in the opinion of the investigator would make the subject unsuitable for inclusion.
Exclusion criteria for Part 3 Open-Label Extension phase
1. Subject with any clinically significant condition from Part 1, and Part 2, that in the opinion of investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis.
2. Subject who, in the opinion of the investigator or sponsor, is unlikely to be cooperative or able to comply with study procedures, or any other condition which in the opinion of the investigator would make the subject unsuitable for inclusion.

E.5 End points

E.5.1

Primary end point(s)

- Part 1 Induction phase
Percentage of subjects in clinical remission at week 8.
- Part 2 Maintenance phase
Percentage of subjects in clinical remission at week 52

E.5.1.1

Timepoint(s) of evaluation of this end point

- Part 1 Induction phase at week 8.
- Part 2 Maintenance phase at week 52

E.5.2

Secondary end point(s)

Part 1
- The percentage of subjects with endoscopic remission.
- The percentage of subjects with clinical response.
- Change from baseline in partial Mayo score.
- Change in total Mayo score and 9-point modified Mayo score.
Part 2
- The percentage of subjects with endoscopic remission.
- The percentage of subjects with clinical response.
- Change from baseline in partial Mayo score.
- Change in total Mayo score and 9-point modified Mayo score.
- Percentage of subjects in corticosteroid-free remission. Corticosteroid-free is defined as the subjects who discontinue corticosteroid of at least 4 weeks prior to the visit.
- Percentage of subjects who maintain clinical remission.
Part 3
- The percentage of subjects in clinical remission per partial Mayo score. Defined as: total Partial Mayo score ≤ 1.
- The percentage of subjects in corticosteroid-free remission per Partial Mayo score.
- Change from baseline in Partial Mayo score.

E.5.2.1

Timepoint(s) of evaluation of this end point

Part 1
- at week 8.
- at week 8.
- at week 2, 4, and 8.
- at week 8.
Part 2
- at week 52.
- at week 52.
- at week 12, 16, 24, 32, 40, and 52.
- at week 52.
- at week 52, corticosteroid-free is defined as the subjects who discontinue corticosteroid of at least 4 weeks prior to the visit.
- at week 52.
Part 3
- at week E26.
- at week E26.
- at week E2, E12, and E26.

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

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

3 parts in the study, induction - blinded; maintenance - blinded, OLE - open

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Ukraine

China

Georgia

United States

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

LVLS

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 years

E.8.9.2

In all countries concerned by the trial months

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:

250

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

118

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

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

100

F.4.2.2

In the whole clinical trial

368

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

2021-09-11

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-08-19

P. End of Trial
P.	End of Trial Status	Completed

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