Plaque Psoriasis
Conditions
Brief summary
This study is a randomized, double-blind, multicenter, dose-parallel-controlled phase II clinical trial. The study consists of three stages: a 4-week screening period, a 52-week treatment period, and a 12-week follow-up period. For the qualified participants screened, using body weight (≥90 kg or \< 90 kg) and whether participants had a poor response to IL-12/23p40 inhibitors in the past (yes vs no) as stratification factors, they were randomly assigned to two groups in a 1:1 ratio: Group 1 and Group 2. The evaluation of the primary study endpoint, some secondary study endpoints and some other endpoints was completed at 16 weeks. Participants who complete the 52nd week assessment will enter a 12-week safe follow-up period until the end of the study.
Interventions
DRUGSHR-1139
Subcutaneous injection of SHR-1139
DRUGSHR-1139 and SHR-1139 pleacebo
Subcutaneous injection of SHR-1139 and SHR-1139 pleacebo
Sponsors
Guangdong Hengrui Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥ 18 years at the time of signing the informed consent form (ICF), male or female 2. Body mass index was ≥18 kg/m ² at screening 3. A history of plaque psoriasis ≥6 months before randomization, with or without psoriatic arthritis 4. Inadequate response to at least one biologic agent administered at full dose and on a regular schedule prior to screening 5. tParticipants with plaque psoriasis deemed by the investigator suitable for continued biologic therapy 6. Participants voluntarily sign informed consent before the start of any procedures related to the study, able to communicate smoothly with the investigator, understand and comply with the study protocol requirements
Exclusion criteria
1. Diagnosis of psoriasis other than chronic plaque psoriasis at screening or baseline 2. Drug-induced psoriasis 3. Other skin conditions that, in the investigator's opinion, would interfere with psoriasis assessment 4. Concurrent other active autoimmune diseases 5. Prior exposure to drugs targeting the IL-36 receptor 6. Prior exposure to drugs targeting IL-23p19 7. Systemic treatment other than biological agents was received within 4 weeks before baseline 8. Topical treatment for psoriasis was received within two weeks before the baseline 9. Received photochemotherapy within 4 weeks before baseline, or received phototherapy within 2 weeks before baseline 10. Have participated in any clinical study of a drug or medical device within 3 months prior to baseline or within 5 half-lives of the drug 11. The participants had a previous history of lymphocytic hyperplasia 12. Participants had any history of active malignant tumors or malignant tumors within the five years prior to screening 13. Participants with a history of moderate to severe congestive heart failure, cardiovascular and cerebrovascular events, or severe bleeding events within 3 months prior to screening were considered unsuitable for clinical research by the researchers 14. There was a history of opportunistic infection or immunodeficiency disease within 6 months prior to screening 15. If there was an active infection within 2 weeks before baseline requiring oral anti-infection treatment, or if there was a severe infection or systemic infection within 4 weeks before baseline requiring intravenous anti-infection treatment or hospitalization due to infection, or other chronic, recurrent, and active infections that the researcher judged as unsuitable for participation in this study 16. There is active tuberculosis or latent tuberculosis infection 17. Positive human immunodeficiency virus antibody (HIV), or positive hepatitis C virus (HCV) antibody test and positive quantitative hepatitis C ribonucleic acid (HCV-RNA) during screening; Or positive for hepatitis B surface antigen (HBsAg) 18. Patients with severe, progressive, uncontrolled cardiovascular and cerebrovascular, liver, kidney, lung, gastrointestinal, hematopoietic system, endocrine, nervous system, mental system, skin and mucous membrane diseases, etc., as well as other conditions that researchers consider unsuitable for participation in this trial 19. The following situations occur in laboratory tests and/or 12-lead electrocardiogram (ECG) during screening: Aspartate aminotransferase (AST) or ALT is three times or more greater than the upper limit of the normal value (ULN). Total bilirubin \> 1.5 times ULN; Serum creatinine \> 1.5 times ULN; The hemoglobin level was less than 85.0 g/L for male participants and less than 80.0 g/L for female participants. White blood cell count \< 3.0 \*109/L; Neutrophil count \< 1.5 \*109/L; Platelet count \< 100\*109/L; The 12-lead ECG examination indicated clinically significant abnormalities that might affect the safety of the participants, including but not limited to acute myocardial ischemia, myocardial infarction, and severe arrhythmia. 20. Pregnant or lactating female, or testing positive for human chorionic gonadotropin (hCG) 21. Allergic to the investigational drug (including SHR-1139 injection and placebo) or any component in the investigational drug; Or those with a clear history of allergy to monoclonal antibodies or drugs targeting the same action; Or those with a history of severe drug allergies 22. There was a history of alcohol abuse or illegal drug abuse within one year prior to the screening 23. Those who received a live attenuated vaccine within 12 weeks before randomization, or intended to receive a live attenuated vaccine during the study period, or participated in a vaccine clinical trial within 12 weeks before randomization 24. Donate approximately 500 mL of blood within the 8 weeks prior to randomization or have a blood donation plan during the study period 25. Those who have undergone major surgery within 8 weeks prior to screening or have relevant surgical plans during the study period 26. The researchers judged that there were situations that affected the safety and efficacy evaluation of the investigational drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants with a sPGA response of 0 or 1 at week 16. | at week 16 |
Secondary
| Measure | Time frame |
|---|---|
| The proportion of participants whose PASI score improved by at least 90% compared to the baseline in week 16 (reaching PASI 90) | week 16 |
| The proportion of participants whose PASI score improved by at least 75% compared to the baseline in week 16 (reaching PASI 75) | week 16 |
| The proportion of participants whose PASI score improved by at least 100% compared to the baseline in week 16 (reaching PASI 100) | week 16 |
| The proportion of participants with a 0 sPGA response in week 16 | week 16 |
| The proportion of participants with a sPGA response of 0 or 1 at all other visits every four weeks, up to 64 weeks | up to 64 weeks |
| The proportion of participants reaching PASI 90 at all other visits every four weeks, up to 64 weeks | up to 64 weeks |
| The proportion of participants reaching PASI 75 at all other visits every four weeks, up to 64 weeks | up to 64 weeks |
| The proportion of participants reaching PASI 100 at all other visits every four weeks, up to 64 weeks | up to 64 weeks |
| The proportion of participants with a sPGA response of 0 at all other visits every four weeks, up to 64 weeks | up to 64 weeks |
| The change values and percentage of change in PASI scores at each visiting point every four weeks relative to the baseline, up to 64 weeks | up to 64 weeks |
| Among the participants with a baseline pruritus score (NRS) of ≥4, the proportion of those with an improvement of ≥4 at week 16 | week 16 |
| The proportion of participants who achieved a dermatological quality of life index (DLQI) of 0 or 1 at week 16 | week 16 |
| The change in NRS scores at each visit point every four weeks relative to the baseline and the percentage of change, up to 64 weeks | up to 64 weeks |
| The change values and percentage changes of DLQI scores at each visiting point every four weeks relative to the baseline, up to 64 weeks | up to 64 weeks |
| The time from randomization to 16 weeks when the sPGA response first reached 0 or 1 | 16 weeks |
| The time from randomization to 16 weeks when the sPGA response first reached 0 | 16 weeks |
| The time when participants first reached PASI 75 from randomization to 16 weeks | 16 weeks |
| The time when participants first reached PASI 90 from randomization to 16 weeks | 16 weeks |
| The proportion of participants who achieved an sPGA response of 0 or 1 in week 16 and still achieved an sPGA response of 0 or 1 in week 26 | week 26 |
| The proportion of participants who achieved PASI 75 in week 16 and still reached PASI 75 in Week 26 | Week 26 |
| The proportion of participants who achieved PASI 90 in week 16 and still reached PASI 90 in week 26 | week 26 |
| The proportion of participants who achieved an sPGA response of 0 or 1 in week 16 and still achieved an sPGA response of 0 or 1 in week 52 | week 52 |
| The proportion of participants who achieved PASI 75 in week 16 and still reached it in Week 52 | Week 52 |
| The proportion of participants who achieved PASI 90 in week 16 and still reached it in week 52 | week 52 |
| The proportion of participants who achieved an sPGA response of 0 or 1 in week 26 and still achieved an sPGA response of 0 or 1 in week 52 | week 52 |
| The proportion of participants who achieved PASI 75 in week 26 and still reached it in Week 52 | Week 52 |
| The proportion of participants who achieved PASI 90 in week 26 and still reached it in week 52 | week 52 |
| Safety and tolerability: Adverse events, up to 68 weeks | up to 68 weeks |
| PK: The concentration of SHR-1139 in serum at week0,1,4,8,16,26,28,44,64 | at week0,1,4,8,16,26,28,44,64 |
| Immunogenicity: The positive incidence rate of ADA at week 0,8,16,26,44,64 | at week 0,8,16,26,44,64 |
| Immunogenicity: The positive occurrence time of ADA at week 0,8,16,26,44,64 | at week 0,8,16,26,44,64 |
| Biomarker: Inhibition rate of IFNγ activation and release in whole blood at each time point after administration at week0,1,4,8,16,26,28,44,64 | at week0,1,4,8,16,26,28,44,64 |
Countries
China
Contacts
CONTACTYijia Xu
Outcome results
None listed