A Phase Ⅲ, Multicenter, Randomized, Double-blind, Placebo Controlled Trial Evaluating the Efficacy and Safety of Tildrakizumab in the Treatment of Chinese Subjects With Moderate to Severe Plaquetype Psoriasis
Overview
- Phase
- Phase 3
- Intervention
- Tildrakizumab 100 mg
- Conditions
- Plaque Psoriasis
- Sponsor
- Shenzhen Kangzhe Pharmaceutical Co., Ltd.
- Enrollment
- 220
- Locations
- 1
- Primary Endpoint
- The proportion of subjects with at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75) at Week 12 from baseline in each group.
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a phase Ⅲ, randomized, double-blind, placebo-controlled, parallel design, multicenter trial to evaluate the efficacy, safety, tolerability, and immunogenicity of subcutaneous Tildrakizumab in subjects with moderate to severe chronic plaque psoriasis.
The trial was divided into two parts: the base study (Week 0- Week 12) and the extension study (Week 13- Week 54).
Detailed Description
Base Study： 220 subjects were randomized in a 1: 1 ratio into the trial, and the treatment group received 100 mg subcutaneous Tildrakizumab at Week 0 and Week 4, 100 mg subcutaneous placebo at Week 12, while the placebo group received 100 mg subcutaneous placebo at Week 0 and Week 4, and 100 mg subcutaneous Tildrakizumab at Week 12, and subjects will be evaluated for efficacy, safety, tolerability, and immunogenicity as specified in this protocol. At the end of the base study, procedures such as data cleaning, locking and unblinding of base study data were performed. Extension Study： Subjects entered the extension study after completion of the base study and will receive 100 mg subcutaneous Tildrakizumab at Week 16, 28, 40, and 52, and will be evaluated for efficacy, safety, tolerability, and immunogenicity by the investigator according to the regulations of this study. At the end of the extension study, all data from the extension study will be entered into the database, after the data is reviewed, cleaned, and locked, the entire trial will be analyzed.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must give a written, signed and dated informed consent.
- •Subject must be 18-70 years of age, of either sex.
- •Diagnosis of predominantly plaque psoriasis for over 6 months (Plaque psoriasis in stable phase, and in non-progressive phase as determined by subject interview and confirmation of diagnosis through physical examination by investigator).
- •Subject is considered to be a candidate for phototherapy or systemic therapy.
- •Psoriasis BSA involvement ≥ 10% at baseline.
- •PASI score ≥ 12 at baseline.
- •PGA of at least moderate disease (≥ 3) at baseline.
- •No history of active TB or symptoms of TB; No recent history of intimate contact with patients with active TB;
- •Subject is a male or a non-sterilized, pre-menopausal female and agrees to abstain from heterosexual activity OR use a medically accepted method of contraception OR use appropriate effective contraception as per local regulations or guidelines. Medically accepted methods of contraception include, but are not limited to, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed IUD, inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (e.g., hysterectomy or tubal ligation).
- •For a woman of childbearing potential, a negative serum pregnancy test at Screening/baseline.
Exclusion Criteria
- •Presence of predominantly non-plaque forms of psoriasis：guttate psoriasis, erythrodermic psoriasis, pustular psoriasis, medication-induced or medication-exacerbated psoriasis.
- •Subjects who are expected to require additional topical therapy, phototherapy, or systemic therapy other than trial drug for the treatment of psoriasis during the trial.
- •Presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or severe infection (e.g., pneumonia, cellulitis, bone, or joint infections) requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to Screening.
- •Subject is known to be allergic to Tildrakizumab or related excipients.
- •Women of childbearing potential who are pregnant or are lactating, female subject or male subject with partner intend to become pregnant (during the trial OR within 6 months of the last administration of the trial drug).
- •Positive human immunodeficiency virus (HIV) antibody (HIV Ab)test result and/or positive Treponema pallidum-specific antibody test result, and/or positive hepatitis C virus antibody (HCV Ab) test result with positive HCV-RNA reverse transcription polymerase chain reaction test result, indicating a past or current infection of hepatitis C virus; and/or positive result of hepatitis B surface antigen (HbsAg) , or positive result of hepatitis B core antibody (HBcAb) with positive result of HBV-DNA polymerase chain reaction test, indicating an current infection of HBV; .
- •Subject has the following clinically significant abnormal laboratory tests according to the investigators' evaluation.
- •Prior malignancy or concurrent malignancy (excluding successfully treated basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma with no evidence of recurrence within 5 years or carcinoma in situ of the cervix that has been adequately treated).
- •Subject who has received a live attenuated vaccine within 4 weeks prior to first dose or who intends to receive live attenuated vaccine during the trial.
- •Subject who is currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 4 weeks prior to first dose.
Arms & Interventions
Tildrakizumab
Subjects will receive 100 mg subcutaneous (SC) Tildrakizumab at Week 0 and Week 4, 100 mg subcutaneous placebo at Week 12. Subjects entered the extension study after completion of the base study and will receive 100 mg subcutaneous Tildrakizumab at Week 16, 28, 40, and 52.
Intervention: Tildrakizumab 100 mg
Placebo
Subjects will receive 100 mg subcutaneous placebo at Week 0 and Week 4, and 100 mg subcutaneous Tildrakizumab at Week 12. Subjects entered the extension study after completion of the base study and will receive 100 mg subcutaneous Tildrakizumab at Week 16, 28, 40, and 52.
Intervention: Placebo
Outcomes
Primary Outcomes
The proportion of subjects with at least 75% improvement in the Psoriasis Area and Severity Index (PASI 75) at Week 12 from baseline in each group.
Time Frame: Week 12
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the area of involvement. Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status.
Secondary Outcomes
- Change from baseline in the Dermatology Life Quality Index (DLQI) at Week 12 in each group.(Week 12)
- The proportion of subjects in each group with a Physician's Global Assessment (PGA) score of "clear" or "minimal" and at least a 2-grade reduction from baseline at Week 4, 8, and 12.(Week 4, 8, and 12)
- Change from baseline in PASI 75, 90, and 100 responses over time from Week 0 to Week 12 in each group.(Week 12)