Psoriasis
Conditions
Brief summary
This study is a Multicenter, Open-Label, Single-Arm Phase III Clinical Trial to Evaluate the Efficacy and Safety of LZM012 Injection in Patients With Moderate to Severe Plaque Psoriasis.
Interventions
BIOLOGICALLZM012
Recombinant anti-human IL-17A/F humanized monoclonal antibody injection
Sponsors
Livzon Pharmaceutical Group Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged ≥18 years at screening, male or female. 2. History of psoriasis for ≥6 months prior to screening, diagnosed as plaque psoriasis according to the Chinese Guidelines for the Diagnosis and Treatment of Psoriasis (2023 Edition) at screening, and considered by the investigator to be suitable for systemic therapy. 3. Meeting all three of the following criteria at screening: (A)PASI score ≥10; (B)sPGA score ≥3; (C)BSA ≥10%. 4. Female participants of childbearing potential must agree to have no pregnancy or egg donation from the time of signing the informed consent form to the end of the study, and voluntarily use highly effective contraceptive measures, except for postmenopausal women; male participants must agree to have no pregnancy (of partner) or sperm donation from the time of signing the informed consent form to the end of the study, and voluntarily use highly effective contraceptive measures. Menopause is defined as meeting one of the following: a) history of bilateral oophorectomy or hysterectomy; b) age ≥55 years, with amenorrhea for ≥12 months without other pathological or physiological reasons; c) age \<55 years, with amenorrhea for ≥12 months without other pathological or physiological reasons, and estradiol (E2) \<20 pg/mL or follicle-stimulating hormone (FSH) \>40 mIU/mL. 5. Ability to understand and comply with the protocol requirements, and voluntary participation in the clinical trial.
Exclusion criteria
1. History of severe allergic reaction to biological agents, or previous history of severe drug allergy. 2. Presence of inflammation, ulceration, induration, scar, mass, or other conditions at the injection site that, in the investigator's opinion, preclude subcutaneous injection administration. 3. Presence of other types of psoriasis at screening, including but not limited to erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, drug-induced psoriasis (including new onset or exacerbation of psoriasis caused by β-blockers, non-steroidal anti-inflammatory drugs, antimalarials, interferons, calcium channel blockers, or lithium). 4. Presence of severe skin infection, eczema, seborrheic dermatitis, neurodermatitis, or other skin conditions at screening that, in the investigator's assessment, may interfere with the evaluation of psoriasis treatment efficacy. 5. Meeting any of the following conditions: (A)Diagnosed with active tuberculosis infection, including but not limited to active tuberculosis confirmed by imaging; (B)Latent tuberculosis infection or close contact with a tuberculosis patient, except in the following cases: a) confirmed by a specialist that standard treatment for latent tuberculosis infection has been completed within 5 years prior to the first dose; b) prophylactic anti-tuberculosis treatment has been initiated at least 4 weeks before the first dose and the subject is willing to continue prophylaxis according to local guidelines; c) the specialist judges that the risk of progression to active tuberculosis is low and that treatment is not required. Latent tuberculosis infection is defined as: positive interferon-gamma release assay (IGRA) at screening, without any clinical signs or symptoms of active tuberculosis. Close contact with a tuberculosis patient is defined as: having had close contact (i.e., spending several days or weeks together in a relatively enclosed space) with a patient with active pulmonary tuberculosis within the past 12 months, or having a family member diagnosed with active tuberculosis infection. 6. History of severe immunodeficiency, including: positive human immunodeficiency virus (HIV) antibody, or other acquired or congenital immunodeficiency diseases. 7. Presence of any of the following clinically significant conditions: (A)History of chronic congestive heart failure with NYHA Class IV; history of echocardiographic cardiac ejection fraction (EF) below 30%; (B)Myocardial infarction, acute coronary syndrome, viral myocarditis, or pulmonary embolism within 6 months prior to screening; coronary revascularization within 6 months prior to screening; (C)History of severe arrhythmias requiring treatment with Class Ia or Class III antiarrhythmic drugs; history of sick sinus syndrome, second-degree type II or third-degree atrioventricular block without an implanted pacemaker; (D)Screening ECG showing QTc interval ≥480 ms (Fridericia correction formula, QTc = QT/(RR\^0.33)), or history of prolonged QTc interval and assessed by the investigator as having arrhythmia risk; (E)Poorly controlled hypertension within 3 months prior to screening (poorly controlled defined as: blood pressure still not reaching target despite combination therapy with ≥3 antihypertensive agents), or screening systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg confirmed by repeated measurements; (F)History of severe psychiatric disorders such as depression, schizophrenia, schizoaffective disorder, or history of suicidal ideation or suicidal behavior; (G)History of severe neurological disorders such as stroke or epilepsy; (H)Active bleeding disorders of internal organs, or severe bleeding tendency (e.g., hemophilia); (I)Other progressive or uncontrolled systemic diseases that, in the investigator's assessment, may be unstable or may become severe during the trial, making the subject unsuitable for participation. 8. Meeting either of the following: a) any severe infection within 1 month prior to screening (defined as infection requiring hospitalization or intravenous anti-infective treatment); b) history of opportunistic infections or recurrent, chronic infections that, in the investigator's opinion, could lead to study discontinuation. Opportunistic infections include infections caused by unusual pathogens (e.g., Pneumocystis jirovecii, cryptococcus, etc.) or unusually severe infections caused by common pathogens (e.g., cytomegalovirus, herpes virus, etc.). 9. History of cancer within 5 years prior to screening, except for cured cutaneous basal cell carcinoma or Stage I squamous cell carcinoma. 10. History of alcohol abuse (defined as consumption of 14 units of alcohol per week: 1 unit = 285 mL beer, or 25 mL spirits, or 100 mL wine) or history of illicit drug use within 1 year prior to screening. 11. Presence of active autoimmune diseases other than psoriasis or psoriatic arthritis (e.g., inflammatory bowel disease, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, inflammatory myopathies, mixed connective tissue disease, overlap syndrome, etc.). 12. Use of topical anti-psoriatic drugs or physical therapy within 2 weeks prior to screening (see prohibited medications/therapies for details). 13. Use of systemic anti-psoriatic drugs other than biologics within 4 weeks prior to screening (see prohibited medications for details). 14. Use of TNF-α inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, or IL-17 inhibitors within 3 months or 5 half-lives (whichever is longer) prior to screening (see prohibited medications for details). 15. Previous participation in and receipt of study drug in the LZM012 clinical trial. 16. Participation in any clinical trial of an investigational drug (defined as having received study drug) within 3 months or 5 half-lives of the investigational drug (whichever is longer) prior to screening. 17. Any of the following laboratory results at screening: (A)Hematology: hemoglobin (HGB) \<90 g/L; platelet count (PLT) \<100 × 10⁹/L; white blood cell count (WBC) \<3 × 10⁹/L; absolute neutrophil count (NEUT) \<1.5 × 10⁹/L; (B)Liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of normal (ULN), or total bilirubin \>1.5 times ULN; (C)Renal function: serum creatinine \>1.5 times ULN. 18. Receipt of a live vaccine (including attenuated live vaccine) within 3 months prior to screening, or planned receipt of a live vaccine (including attenuated live vaccine) during the trial. 19. Meeting any of the following at screening: (A)Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with further testing showing HBV-DNA ≥500 IU/mL; (B)Positive hepatitis C virus (HCV) antibody with further testing showing HCV RNA positive; (C)Positive syphilis specific antibody with further testing showing positive syphilis non-specific antibody (including but not limited to rapid plasma reagin (RPR) test, toluidine red unheated serum test (TRUST), etc.). 20. Pregnant or breastfeeding women, or positive pregnancy test result at screening. 21. Any other condition or situation that, in the investigator's opinion, makes the subject unsuitable for participation in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PASI100 response rate | At week 12 | The ratio of patients reached PASI100 (PASI100 response rate) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to first achievement of PASI50, PASI75, PASI90 and PASI100 | Up to Week 12 | — |
| PASI75/PASI90 response rate | At week 4、 At week 8、 At week 12 | — |
| Absolute and relative percentage change from baseline in PASI score at each visit | at Week 4, Week 8, Week 12 | — |
| sPGA 0/1 response rate | At week 4、 At week 8、 At week 12 | — |
| change in Dermatology Life Quality Index (DLQI) score | At week 4、 At week 8、 At week 12 | Dermatology Life Quality Index (DLQI) Score range: 0 to 30; higher scores indicate worse health-related quality of life. |
| treatment-emergent adverse events | up to week 16 | — |
| Vital signs: systolic blood pressure | Up to Week 16 | — |
| Vital signs: diastolic blood pressure | Up to Week 16 | — |
| Vital signs: pulse rate | up to week 16 | — |
| Vital signs: tympanic temperature | up to week 16 | — |
| Electrocardiogram (ECG): PR interval, QT interval | Up to Week 16 | — |
| Electrocardiogram (ECG): heart rate | up to week 16 | — |
| physical examinatio: Proportion of subjects with abnormal skin findings on physical examination | Up to Week 16 | — |
| physical examination:Proportion of subjects with abnormal head and neck findings on physical examination | up to week 16 | — |
| physical examination:Proportion of subjects with abnormal chest findings on physical examination | up to week 16 | — |
| physical examination:Proportion of subjects with abnormal abdomen findings on physical examination | up to week 16 | — |
| physical examination:Proportion of subjects with abnormal extremities findings on physical examination | up to week 16 | — |
| Incidence of anti-drug antibody (ADA) and neutralizing antibody (NAb) positive | From baseline to Week 12 | — |
| Laboratory tests: hematology：Platelet count, Neutrophil count, Lymphocyte count, White blood cell (WBC) count | up to week 16 | — |
| Laboratory tests: hematology:Hemoglobin (Hb) | up to week 16 | — |
| Laboratory tests: hematology:Hematocrit (Hct), Neutrophil percentage | up to week 16 | — |
| Laboratory tests: serum biochemistry:Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), Creatine phosphokinase (CPK) | up to week 16 | — |
| Laboratory tests: serum biochemistry:Total bilirubin (TBIL), Direct bilirubin (DBIL), Creatinine (Cr), Uric acid (UA); | up to week 16 | — |
| Laboratory tests: serum biochemistry:Total cholesterol (TC), Triglycerides (TG), Low-density lipoprotein cholesterol (LDL-C), Glucose (GLU) | up to week 16 | — |
| Laboratory tests: urinalysis:Urine protein, urine glucose, urine ketone bodies; | up to week 16 | — |
| Laboratory tests: urinalysis:Urine leukocytes, urine erythrocytes | up to week 16 | — |
Countries
China
Outcome results
None listed