Clinical trial NCT06542614: Treatment of Moderate to Severe Plaque Psoriasis
Official title: A Phase II Clinical Trial to Evaluate the Efficacy, Safety, Pharmacokinetics (PK), and Pharmacodynamic (PD) Profile of TQH3906 in Subjects With Moderate to Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Plaque Psoriasis
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-07
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To assess the efficacy and safety of TQH3906 in subjects with moderate to severe plaque psoriasis, as well as the PK and PD characteristics of multiple doses


Eligibility criteria: Inclusion Criteria:

* Be 18-70 years old (both 18 and 70 years old), regardless of gender；
* Clinically diagnosed with stable moderate to severe plaque psoriasis with a history ≥ 6 months (from randomization), and no morphological changes in skin lesions or significant disease outbreaks as assessed by the investigator;
* Appropriate for systemic therapy or phototherapy as judged by the investigator;
* At screening and baseline, the PASI score was ≥ 12 points, the BSA ≥ 10%, and the sPGA ≥ 3 points ;
* Have a full understanding of this study, voluntarily participate in the trial, and have signed a written informed consent form;
* Subjects (including partners) are willing to voluntarily use appropriate and effective contraceptive measures from screening to 3 months after the last dose of study drug.

Exclusion Criteria:

* Pregnant and lactating females;
* Have other forms of psoriasis other than plaque psoriasis (e.g., guttate psoriasis, generalized pustular psoriasis, erythrodermic psoriasis, arthropathic psoriasis);
* Presence of serovirological abnormalities during the screening period:

  1. Active hepatitis, or hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcA positive and Hepatitis B virus (HBV) DNA positive, or Hepatitis C virus (HCV) antibody positive and HCV-RNA positive;
  2. Positive for HIV antibody during the screening period, or have a history of HIV infection in the past;
  3. Positive Treponema pallidum antibody and positive non-Treponema pallidum serum test (RPR or TRUST) during the screening period;
* Have a history of active tuberculosis during the screening period or before, or have latent tuberculosis infection found at screening (refers to T-SPOT positive without clinical manifestations). (Note: Patients with latent tuberculosis infection can be re-screened 1 month after starting prophylaxis according to the guidelines, and in order to continue to participate in the study, patients must agree to continue to complete the prophylactic regimen during the study, but rifampicin treatment should be avoided.) ;
* Has a history of severe herpes zoster or herpes simplex infection, including but not limited to herpetic encephalitis, disseminated herpes simplex, generalized herpes zoster;
* History of severe bacterial, fungal or viral infection within 2 months prior to randomization, requiring hospitalization for intravenous antibiotics or antiviral drug treatment;
* Live vaccine within 4 weeks prior to randomization or planned live vaccine during the study;
* Clinically significant infection, including but not limited to upper respiratory tract infection, lower respiratory tract infection, herpes simplex, herpes zoster, during the screening period, and requiring antibiotic or antiviral medication treatment;
* Has any significant illness or unstable clinical condition (such as renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, psychiatric, neurological, immune, or locally active infectious/infectious disease) that is judged by the investigator to be unsuitable for participation in this study.
* Abnormal laboratory tests during the screening period:

  1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 3 times upper limit of normal (ULN);
  2. Hemoglobin \<90g/L;
  3. White blood cell count\< 3.0×109/L;
  4. Neutrophil count\<1.0×109/L;
  5. Lymphocyte count\<0.5×109/L;
  6. Platelet count \< 100×109/L;
  7. Total bilirubin \>2 times ULN;
  8. Other significant laboratory test abnormalities that, in the opinion of the investigator, the subject is not suitable for participation in this study.
* History of malignant tumors (including carcinoma in situ) and lymphoproliferative disorders within 5 years prior to randomization;
* Those who have received anti-IL-12, IL-17, Interleukin 23 (IL-23) monoclonal antibody therapy (such as ustekinumab, secukinumab, Ixekizumab, guselkumab, adalimumab, etc.) within 6 months prior to randomization, or those who have received at least 12 consecutive times of the above drugs in the past but have poor clinical response (defined as not achieving PASI 50 during treatment);
* Receipt of any other marketed or investigational biologic agent within 3 months or 5 half-lives (whichever is longer) prior to randomization;
* Receipt of any other investigational drug in 1 month or 5 half-lives (whichever is longer) prior to randomization;
* Those who have undergone surgical surgery within 4 weeks prior to randomization, or who plan to undergo surgical procedures during the study;
* Those who have lost blood or donated more than 400 mL of blood within 4 weeks prior to randomization;
* Receipt of immunoglobulin or blood products within 4 weeks prior to randomization;
* Systemic treatment drugs or immunosuppressants for psoriasis within 4 weeks prior to randomization, including but not limited to retinoids, glucocorticoids, methotrexate, cyclosporine, azathioprine, Janus kinase (JAK) inhibitors, etc;
* Use of strong CYP450 inducers (such as rifampicin, phenobarbital, carbamazepine, phenytoin, etc.) within 4 weeks prior to randomization;
* Received topical or systemic phototherapy within 4 weeks prior to randomization, including but not limited to Narrow-band ultraviolet B (NB-UVB), photochemotherapy (PUVA), 308nm excimer light;
* Use of topical drugs that may affect the severity of skin lesions in psoriasis within 2 weeks prior to randomization, including but not limited to glucocorticoids, urea, \>3% salicylic acid, α or β hydroxy acids, retinoids, vitamin D3 analogues, calcineurin inhibitors, Phosphodiesterase-4 (PDE-4) inhibitors, etc. (Note: Mild emollients (without active substances such as urea, salicylic acid, α, or β hydroxy acids) are allowed to be used at all sites, but should not be used within 24 hours prior to each study visit);
* Potential difficulty in blood collection, with a history of fainting needle and blood sickness;
* Allergy to any of the known ingredients of the TQH3906, or any previous history of severe drug allergies.
* Those with a history of substance abuse or a positive urine drug screen;
* Has any other reasonable medical, psychiatric, or social reason that, in the opinion of the investigator, precludes participation in this study.

Primary outcomes:
measure: Proportion of patients achieving Psoriasis Area and Severity Index (PASI) 75 at week 12
timeFrame: Up to week 12
Secondary outcomes:
measure: Proportion of patients achieving Static Physician's Global Assessment (sPGA) 0/1 at week 12
timeFrame: Up to week 12
measure: Proportion of patients achieving PASI 50 at week 12
timeFrame: Up to week 12
measure: Proportion of patients achieving PASI 90 at week 12
timeFrame: Up to week 12
measure: Proportion of patients achieving PASI 100 at week 12
timeFrame: Up to week 12
measure: Body Surface Area (BSA) score
timeFrame: Up to week 12
measure: Dermatology Life Quality Index (DLQI) score
timeFrame: Up to week 12
measure: Incidence of abnormal laboratory test markers
timeFrame: From randomization to 4 weeks after the last dose
measure: Adverse event (AE)
timeFrame: From randomization to 4 weeks after the last dose
measure: Serious Adverse Events (SAEs)
timeFrame: From randomization to 4 weeks after the last dose.
measure: Tmax, ss
timeFrame: Within 1 hour before Day1, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours, Day 15, Day 29, Day 57, Day 85 within 1 hour before administration, 1,1.5, 2, 2.5 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 48 hours, 72 hours after Day 85
measure: Cmax, ss
timeFrame: Within 1 hour before Day1, 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours, Day15, Day29, Day57, Day85 within 1 hour before administration, and 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8,12, 24, 48, 72 hours after Day85
measure: Cmin, ss
timeFrame: Within 1 hour before Day1, 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours, Day15, Day29, Day57, Day85 within 1 hour before administration, and 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72 hours after Day85
measure: Area under the plasma concentration-time curve (AUC) 0-τ
timeFrame: Within 1 hour before Day1 administration, 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours, Day15, Day29, Day57, Day85 within 1 hour before administration, and 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72 hours after Day85
measure: Rac
timeFrame: Within 1 hour before Day1 administration, 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours, Day15, Day29, Day57, Day85 within 1 hour before administration, and 1 hour, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72 hours after Day85
measure: Interleukin-17A (IL-17A) in serum
timeFrame: Within 1 hour before Day1 administration, Day15, Day29, Day85
measure: Interleukin 19 (IL-19) in serum
timeFrame: Within 1 hour before Day1 administration, Day15, Day29, Day85
measure: β defensin in serum
timeFrame: Within 1 hour before Day1 administration, Day15, Day29, Day85
Other outcomes:
Locations:
city: Wuhu
country: China
facility: The Second Affiliated Hospital of Wannan Medical College
state: Anhui
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
state: Beijing
city: Chongqing
country: China
facility: The first affiliated hospital of chongqing medical university
state: Chongqing
city: Guangzhou
country: China
facility: Dermatology Hospital of Southern Medical University
state: Guangdong
city: Liuzhou
country: China
facility: Liuzhou People'S Hospital
state: Guangxi
city: Shijiazhuang
country: China
facility: Shijiazhuang Hospital of Traditional Chinese Medicine
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of HeBei Medical University
state: Hebei
city: Xingtai
country: China
facility: The Second Affiliated Hospital Of Xingtai Medical Colledge
state: Hebei
city: Harbin
country: China
facility: Heilongjiang Provincial Hospital
state: Heilongjiang
city: LuoYang
country: China
facility: The Second Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Nanyang
country: China
facility: Nanyang First People'S Hospital
state: Henan
city: Shiyan
country: China
facility: Shiyan Renmin Hospital
state: Hubei
city: Wuhan
country: China
facility: Wuhan First Hospital
state: Hubei
city: Changde
country: China
facility: The First People's Hospital of Changde
state: Hunan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: Baotou
country: China
facility: The First Affiliated Hospital of Baotou Medical College
state: Inner Mongolia
city: Nanjing
country: China
facility: Hospital of Dermatology, Chinese Academy of Medical Sciences
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Yancheng
country: China
facility: Yancheng First People's Hospital
state: Jiangsu
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Meihekou
country: China
facility: Meihekou Central Hospital
state: Jilin
city: Panjin
country: China
facility: Genertec Liaoyou Gem Flower Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The first hospital of china medical university
state: Liaoning
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Shandong First Medical University Affiliated Dermatology Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong University Qilu Hospital
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal hospital (group)
state: Shandong
city: Qingdao
country: China
facility: Qingdao Traditional Chinese Medicine Hospital
state: Shandong
city: Shanghai
country: China
facility: Shanghai JiaoTong University of medicine Ruijin Hospital
state: Shanghai
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital
state: Tianjin
city: Ürümqi
country: China
facility: Xinjiang Uygur Autonomous Region People's Hospital
state: Xinjiang
city: Hangzhou
country: China
facility: Affiliated Hangzhou First People'S Hospital,School of Medicine, Westlake University
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School Of Medicine
state: Zhejiang
Study officials:
References: