Psoriasis
Conditions
Brief summary
This study is a multicenter, randomized, double-blind, placebo- and active-controlled Phase III clinical trial sponsored by Nanjing Shunxin Pharmaceutical Co., Ltd., a subsidiary of Chiatai Tianqing Pharmaceutical Group. The study aims to evaluate the efficacy and safety of once-daily oral TQH3906 capsules (24 mg) in adult participants with moderate to severe plaque psoriasis. TQH3906 is a highly selective TYK2 allosteric inhibitor targeting the JH2 domain, which blocks the IL-23 and Type I interferon inflammatory pathways. Approximately 400 eligible participants aged 18-75 years will be enrolled. Participants will be stratified based on prior biologic use and randomized in a 2:2:1 ratio to the TQH3906 group, the deucravacitinib active control group, or the placebo group. The trial includes a screening period, a 16-week double-blind controlled treatment phase, a 36-week open-label extension phase (during which all participants will receive TQH3906), and a 4-week safety follow-up after the last dose. The co-primary endpoints are the proportion of participants achieving sPGA 0/1 and PASI 90 response at Week 16. Secondary endpoints include improvements in scalp, nail, and palmoplantar psoriasis, Dermatology Life Quality Index (DLQI), long-term safety, and steady-state pharmacokinetic parameters. This study will collect comprehensive efficacy and safety data over 52 weeks to support the New Drug Application (NDA) for TQH3906 for the treatment of plaque psoriasis.
Interventions
DRUGTQH3906 capsules
TQH3906 Capsules is an inhibitor that targets tyrosine kinase 2 (TYK2).
DRUGDeucravacitinib tablets 6 mg
Deucravacitinib tablet is an inhibitor that targets tyrosine kinase 2 (TYK2).
DRUGTQH3906 Capsules placebo
No pharmacologically active substance
DRUGDeucravacitinib tablets placebo
No pharmacologically active substance
Sponsors
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Participants must be between 18 and 75 years old when signing the informed consent form (ICF), regardless of gender; 2. Confirmed diagnosis of plaque psoriasis for at least 6 months at screenin 3. Disease is stable at screening and baseline visits, and the following criteria are met: * Static Physician Global Assessment (sPGA) score ≥3; * Psoriasis Area and Severity Index (PASI) score ≥12; * Body Surface Area (BSA) affected by psoriasis ≥10%; 4. Deemed by the Investigator as suitable for systemic therapy or phototherapy; 5. Women of childbearing potential must have a negative pregnancy test at screening and baseline visits. Women of childbearing potential and male trial participants whose spouse or partner is a woman of childbearing potential must be willing to use at least one effective method of contraception as specified in the protocol during the study period (from signing the ICF until 30 days after the last dose of investigational drug). Male trial participants must also commit to not donating sperm during the study period and within 30 days after the last dose of study drug; 6. Before initiating any screening or study-specific procedures, trial participants must be able to understand and willing to comply with all protocol requirements, and voluntarily sign and date the ICF.
Exclusion criteria
1.Presence of non-plaque psoriasis during the Screening period or at the Baseline visit; 2.Past or current diagnosis of drug-induced psoriasis; 3.Concomitant other autoimmune diseases, including but not limited to rheumatoid arthritis, sarcoidosis, and systemic lupus erythematosus; 4.Receiving therapeutic agents for psoriatic arthritis (PsA) other than stable-dose non-steroidal anti-inflammatory drugs (NSAIDs) or analgesics. 5.Prior exposure to TQH3906 Capsules or Deucravacitinib Tablets; 6.Receipt of any of the following medications or treatments within the specified time window: 1. Any topical agents or treatments that may interfere with psoriasis assessment, administered within 2 weeks before the Baseline visit; 2. Psoriasis phototherapy administered within 4 weeks before the Baseline visit; 3. Any biologics or biosimilars thereof, administered within the specified time frame before the Baseline visit; 4. Systemic non-biologic psoriasis therapy and/or systemic immunosuppressive treatment administered within 4 weeks before the Baseline visit; 5) Within 6 months prior to the baseline visit: Leflunomide; 6) Within 4 weeks prior to the baseline visit: Traditional Chinese medicines (TCM), Chinese proprietary medicines, or herbal preparations used for psoriasis treatment or with unknown composition/nature, including but not limited to Total Glucosides of Paeony, Tripterygium wilfordii preparations, Compound Glycyrrhizin preparations, Compound Qingdai preparations, etc.; 7) Within 4 weeks prior to the baseline visit: Any live vaccines or live-attenuated vaccines; OR anticipated need to receive live vaccines or live-attenuated vaccines during the study period including at least 4 weeks after the last dose of investigational product; 8) Within 3 months prior to the baseline visit (or 5 half-lives, whichever is longer): Investigational biological agent treatment; OR within 30 days prior to the baseline visit (or 5 half-lives, whichever is longer): Any other investigational drug treatment; OR currently participating in other clinical trials; 7. Active infection/history of infection, or receipt of specific anti-infective therapies within the specified time windows; 8. Previous or current presence of severe or unstable diseases or medical conditions involving neurological, cardiovascular, respiratory, digestive, urinary, hematological, or immune systems that, in the Investigator's judgment, may interfere with outcome assessment or affect participation safety 9. Laboratory test abnormalities meeting any of the following criteria during the screening period: 1) Hemoglobin \<90.0 g/L; 2) White blood cell count \<3.0×10⁹/L; 3) Neutrophil count \<1.0×10⁹/L; 4) Lymphocyte count \<0.5×10⁹/L; 5) Platelet count \<100×10⁹/L; 6) Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) \>3× Upper Limit of Normal (ULN); 7) Total bilirubin (TBIL) \>1.5× ULN; 8) Estimated creatinine clearance \<45 mL/min calculated based on the Cockcroft-Gault formula. (See Appendix 2 for calculation formula); 9) Thyroid-stimulating hormone (TSH) outside the normal reference range, concomitant with free T4 or T3 also outside the normal reference range. 10\. History of drug or alcohol abuse within 6 months prior to screening; 11. Known allergy, hypersensitivity, or intolerance to TQH3906 capsules, deucravacitinib tablets, or any excipient ingredients; 12. Women who are pregnant, breastfeeding, or planning to become pregnant during the trial, and men who plan to father children or donate sperm during the trial; 13. Trial participants who are employees of the Sponsor, third-party agency staff, or direct research center staff involved in this study or their family members; 14. Per Investigator assessment, presence of any other medical, psychiatric, or other reasons that render the trial participant unsuitable for participation in this study. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| static Physician's Global Assessment (sPGA) | Baseline up to 16 weeks | Proportion of participants achieving sPGA 0/1 at Week 16, comparing participants using TQH3906 capsules versus placebo. |
| Psoriasis Area and Severity Index (PASI) | Baseline up to 16 weeks | Proportion of participants achieving PASI 90 at Week 16, comparing participants using TQH3906 capsules versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| static Physician's Global Assessment (sPGA) | Baseline up to 16 weeks | Proportion of participants achieving sPGA 0/1 at Week 16, comparing participants using TQH3906 capsules versus Deucravacitinib.. |
| Psoriasis Area and Severity Index (PASI) | Baseline up to 16 weeks | Proportion of participants achieving PASI 90 at Week 16, comparing participants using TQH3906 capsules versus Deucravacitinib. |
| Scalp static Physician's Global Assessment (sPGA) | Baseline up to 52 weeks | Proportion of participants achieving sPGA 0 at each assessment visits, comparing participants using TQH3906 capsules versus Deucravacitinib.. |
| Scalp static Physician's Global Assessment (ssPGA) | Baseline up to 52 weeks | Proportion of participants achieving ssPGA 0/1 at each assessment visits, comparing participants using TQH3906 capsules versus placebo. |
| Palmoplantar Psoriasis Physician Global Assessment (pp-PGA) | Baseline up to 52 weeks | Proportion of participants achieving ssPGA 0/1 at each assessment visits, comparing participants using TQH3906 capsules versus placebo. |
| Physician's Global Assessment of Fingernail Psoriasis (PGA-F) | Baseline up to 52 weeks | Proportion of participants achieving PGA-F 0/1 at each assessment visits, comparing participants using TQH3906 capsules versus placebo. |
| Dermatology Life Quality Index (DLQI) | Baseline up to 52 weeks | Change from baseline in Dermatology Life Quality Index (DLQI) at each assessment visit;comparing participants using TQH3906 capsules versus placebo. |
| Psoriatic Lesion Body Surface Area (BSA) | Baseline up to 52 weeks | Change from baseline in Psoriatic Lesion Body Surface Area (BSA) at each assessment visit; comparing participants using TQH3906 capsules versus placebo. |
| Effects on participants' Psoriasis Area and Severity Index (PASI) | Baseline up to 52 weeks | Questionnaire: Psoriasis Area and Severity Index (PASI) total score, range 0-72. The body is divided into 4 regions (head, upper extremities, trunk, lower extremities) weighted by 0.1, 0.2, 0.3, 0.4 respectively. Each region is scored for erythema, induration, desquamation (0-4 each) and lesion area (0-6). Higher scores indicate more severe psoriasis. |
| Effects on participants' static Physician's Global Assessment (sPGA) | Baseline up to 52 weeks | Questionnaire: Static Physician's Global Assessment (sPGA) is a single-item static global severity scale (0-4 points) assessing overall psoriasis lesion severity at a single timepoint, based on equal-weighted evaluation of 3 lesion features: erythema, induration, desquamation (each scored 0-4, averaged to final global score). Scoring grading: 0 = Cleared (no active lesions, residual pigmentation allowed) 1. = Almost cleared 2. = Mild 3. = Moderate 4. = Severe sPGA 0/1 responder = score 0 or 1 at target visit; |
| Effects on participants' Scalp static Physician's Global Assessment (ssPGA) | Baseline up to 52 weeks | Questionnaire: ssPGA is a static 5-point single-item scale (0 to 4) exclusively evaluating scalp psoriatic lesions, comprehensively and equally assessing three lesion features: erythema, plaque induration/thickening, and scaling limited to scalp only. Scoring grading: 0 = Clear 1. = Almost clear 2. = Mild 3. = Moderate 4. = Severe |
| Effects on participants' Palmoplantar Psoriasis Physician Global Assessment (pp-PGA) | Baseline up to 52 weeks | Questionnaire: Palmoplantar Psoriasis Physician Global Assessment (pp-PGA). is a static single-item 5-point scale (score range 0-4), exclusively evaluating plaque psoriasis lesions limited to palms and soles. Investigators equally assess three core lesion features: erythema, hyperkeratosis/induration, scaling (fissures/pain secondary to plaques are referenced as auxiliary manifestations). Grading definition: 0 = Clear 1. = Almost clear 2. = Mild 3. = Moderate 4. = Severe |
| Effects on participants' Physician's Global Assessment of Fingernail Psoriasis (PGA-F) | Baseline up to 52 weeks | Questionnaire: Physician's Global Assessment of Fingernail Psoriasis (PGA-F) is a static single-item 5-point scale (score range 0-4), exclusively evaluating psoriatic lesions of all fingernails. Investigators comprehensively assess core nail psoriasis manifestations: nail pitting, onycholysis, subungual hyperkeratosis, splinter hemorrhages, nail discoloration, crumbling. Grading definition: 0 = Clear 1. = Almost clear 2. = Mild 3. = Moderate 4. = Severe |
| Effects on participants' Dermatology Life Quality Index (DLQI) | Baseline up to 52 weeks | Questionnaire: The Dermatology Life Quality Index (DLQI) is a validated self-administered 10-item patient-reported questionnaire evaluating the impact of skin disease on quality of life over the prior 7 days. The scale covers 6 domains: symptoms \& feelings, daily activities, leisure, work/school, personal relationships, treatment burden. Each question is scored 0 (not at all/not relevant) to 3 (very much); total score ranges from 0 to 30. Lower scores indicate less impairment to quality of life. |
| Adverse event rate | Baseline up to 56 weeks | The occurrence of all adverse events (AEs), serious adverse events (SAEs) ,Adverse Events of Special Interest (AESIs) and treatment-related adverse events (TEAEs). |
| Plasma concentration of TQH3906 at steady state (Cav, SS) | 1 hour Pre-dose of day 1 and 30 minutes Pre-dose of day 29, day 57, day 113, day 225, day 365 during treatment. | The plasma concentration at which the rate of administration and rate of elimination are in equilibrium. |
Countries
China
Contacts
CONTACTXinghua Gao, Doctor
Outcome results
None listed