A phase 3 Study to Evaluate the Efficacy and Safety of SHR0302 in Ulcerative Colitis.
- Conditions
- Moderately to severely active Ulcerative Colitis (UC)MedDRA version: 20.1Level: LLTClassification code 10045365Term: Ulcerative colitisSystem Organ Class: 100000004856Therapeutic area: Diseases [C] - Digestive System Diseases [C06]
- Registration Number
- EUCTR2021-001940-86-PL
- Lead Sponsor
- Reistone Biopharma Company Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 368
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Ad
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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method