Clinical trial NCT05970432: A Clinical Study of TQH2722 Injection in the Treatment of Moderate to Severe Atopic Dermatitis
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Trial Evaluating the Efficacy and Safety of TQH2722 Injection in Subjects With Moderate to Severe Atopic Dermatitis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-08-01
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This phase II clinical trials is multicenter, randomized, double-blind, placebo-controlled to assess the effectiveness and safety of TQH2722 injection in the treatment of subjects with moderate to severe atopic dermatitis.


Eligibility criteria: Inclusion Criteria:

* Age 18-65 (when signing informed consent), regardless of gender;
* Meets 2014 American Academy of Dermatology (AAD) criteria with diagnosis of atopic dermatitis (AD); In addition, history of AD prior to screening ≥ 6 months; Eczema was previously diagnosed but met the 2014 AAD criteria and can still be enrolled.
* Patients with moderate to severe AD at screening and baseline visit (shall meet all 3 criteria as follows):

  1. total area of AD lesions≥ 10% BSA;
  2. IGA ≥3 points;
  3. EASI ≥ 16 points;
* Baseline peak pruritus NRS ≥4 (The average peak pruritus intensity score in baseline peak pruritus NRS will be calculated based on the average of the peak pruritus intensity NRS score (daily score range 0-10) for each day during the 7 days prior to randomization. A minimum of 4 days out of 7 days of scoring is required to calculate the baseline average score. If the patient's reporting days are less than 4 days in the 7 days prior to the planned randomization date, randomization should be postponed until the requirements are met, but not beyond the maximum period of 14 days for screening);
* 6 months prior to the screening period, insufficient response to stable (≥1 month) topical corticosteroids (TCS) or calcineurin inhibitors (TCI) (insufficient response defined as at least 28 days even if the daily regimen of moderate-high potency TCS (± topical TCI, if applicable) is at least 28 days, or to the maximum recommended course of treatment (eg, ultra-potent TCS - 14 days) in the product prescribing information (whichever is shorter), Failure to achieve or maintain disease remission or low disease activity (equivalent to IGA 0 \[=none\]-2 \[=mild\]). or patients who have received a record of systemic treatment (adequate dose, adequate course) of AD in the past 6 months are also considered to have insufficient response to topical drug therapy, and may be selected for trial after appropriate drug elution and approval by the sponsor);
* Before the first dose, subjects must have continuously used the emollient twice a day for at least 1 week and maintained throughout the trial (Note: the emollient is provided by the sponsor);
* Be able to read and understand, and be willing to sign informed consent forms;
* Willingness and compliance with research visits and related procedures;
* Female participants of childbearing age should agree that contraception (e.g., intrauterine devices, pills, or condoms) must be used during the study period and for 6 months after the end of the study; Negative serum pregnancy test within 7 days prior to first dose and must be a non-lactating subject; Male subjects should agree that contraception must be used during the study period and for 6 months after the end of the study period.

Exclusion Criteria:

* Participants who received the following treatments within the following limited time prior to randomization:

  1. Have used any of the following treatments within 4 weeks or the investigator believes that the following treatments may be required: immunosuppressants/immunomodulatory drugs (eg, systemic glucocorticosteroids, cyclosporine, mycophenolate mofetil, interferon γ (IFN-γ), azathioprine, and methotrexate); AD phototherapy;
  2. Oral Janus Kinase (JAK) inhibitors (including but not limited to upadacitinib) used within 2 weeks;
  3. Received systemic traditional Chinese medicine (TCM) treatment within 4 weeks; or within 1 week, topical TCM;
  4. Treated with leukotriene inhibitors within 4 weeks;
  5. Treated with topical preparations of TCS or TCI or phosphodiesterase 4 (PDE⁃4) inhibitors within 2 weeks;
  6. Treatment with the following biologics: any cell depleting agent, including but not limited to rituximab: within 6 months or until the lymphocyte count returns to normal, whichever is longer; Other biologics: 5 half-lives (if half-life known) or 12 weeks (whichever is longer); Within 4 weeks, receive regular phototherapy (including but not limited to narrow-spectrum UVB, psoralen longwave ultraviolet therapy, etc.) or use artificial sunbathing sheds/rooms;
  7. Within 12 weeks, receive live (attenuated) vaccine;
  8. Chronic active or acute infection requiring systemic treatment with antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks, or superficial skin infection within 1 week prior to baseline visit. After the infection resolves, screening can be renewed;
  9. Antihistamines (including oral, nasal, and topical preparations) within 1 week;
* Abnormal physical examination results during screening or any of the following laboratory tests:

  1. Hemoglobin\< 110 g/L
  2. White blood cell (WBC) \< 3.5 x 10\^9/L
  3. Platelet count \< 125 x 10\^9/L
  4. Neutrophils\< 1.75 x 10\^9/L • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \>1.5 x upper limit of normal (ULN)
  5. Total bilirubin \> 1.5 x ULN (except indirect bilirubin elevation secondary to Gilbert syndrome)
  6. Creatinine \> 1.5 x ULN
  7. Creatine phosphokinase (CPK) \> 2 x ULN
* There are cutaneous comorbidities that may interfere with the study assessment, including but not limited to scabies, seborrheic dermatitis, cutaneous T-cell lymphoma, psoriasis, etc
* Concomitant other serious medical conditions that, at the discretion of the investigator, may adversely affect participants' participation in this study, including, but not limited to: short life expectancy, history of uncontrolled diabetes (HbA1c ≥ 9%), cardiovascular disease (eg, grade III or IV heart failure, graded according to the New York Heart Association), severe kidney disease (eg, patients on dialysis), hepatobiliary disease (e.g., Child-Pugh class B or C), neurological disease (e.g., demyelinating disease), Patients with important active autoimmune diseases (eg, lupus, inflammatory bowel disease, rheumatoid arthritis, etc.), as well as other severe endocrine, gastrointestinal, metabolic, pulmonary, or lymphatic diseases.
* Have a history of known or suspected immunosuppression, including invasive opportunistic infections (e.g., histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, and aspergillosis), even if the infection has resolved; or unusual frequent, recurrent, or long-term infections (at the investigator's discretion);
* Subjects with any type of active malignancy or a history of malignancy (except cervical cancer or non-metastatic cutaneous squamous cell carcinoma, basal cell carcinoma and papillary thyroid carcinoma) that has been cured for more than 5 years prior to the screening period;
* Computed Tomography (CT) of the chest shows active or occult tuberculosis or a history of contact with an open tuberculosis (TB) subject within the past 6 months. If the laboratory T cell spot test for tuberculosis infection test (or other tuberculosis diagnostic test) is positive, its activity is judged in combination with the medical history, clinical manifestations, etc., and the investigator determines whether it can be enrolled;
* Active hepatitis during the screening period, or positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core antibody (HBcAb);
* History of human immunodeficiency virus (HIV) infection, or positive HIV serological results at screening, and positive antibodies to treponema pallidum during screening
* Positive for treponemal pallidum antibodies during screening
* Parasitic infection related to any of the following is excluded:

  1. Routine inspection of worm eggs during the screening period;
  2. History of parasitic infection within 6 months prior to the screening period, except for cured trichomoniasis;
* Have participated in clinical trials of other drugs or medical devices within 12 weeks prior to screening
* During the period of participation in this study, participants had planned surgical procedures
* Pregnant or lactating women
* People who are alcoholic, drug addicts, and known drug dependents
* In the judgment of the investigator or sponsoring medical auditor, it is believed that there are any medical or psychiatric symptoms that put the subject at risk, interfere with participation in the study, or interfere with the interpretation of the results of the study.

Primary outcomes:
measure: Eczema area and severity (EASI)-75 (≥75% improvement from baseline).
timeFrame: Up to 16 weeks.
Secondary outcomes:
measure: Investigator's general assessment (IGA)
timeFrame: Up to 16 weeks.
measure: Eczema area and severity (EASI)-90 (≥90% improvement from baseline).
timeFrame: Up to 16 weeks.
measure: Eczema area and severity (EASI)
timeFrame: Up to 16 weeks.
measure: Change in investigator's general assessment (IGA)
timeFrame: Up to 16 weeks.
measure: Body surface area (%BSA)
timeFrame: Up to 16 weeks.
measure: Treatment Emergent Adverse Events (TEAE)
timeFrame: Up to 20 weeks.
measure: Incidence of anti-drug antibodies (ADAs)
timeFrame: Up to 24 weeks.
measure: Incidence of neutralizing antibodies
timeFrame: Up to 24 weeks.
measure: Peak Itch numerical rating scale (NRS)
timeFrame: Up to 16 weeks.
measure: Dermatology Life Quality Index (DLQI) scores
timeFrame: Up to 16 weeks.
Other outcomes:
Locations:
city: Wuhu
country: China
facility: The First Affiliated Hospital of Wannan Medical College
state: Anhui
city: Guangzhou
country: China
facility: Dermatology Hospital, Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The Second Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen People's Hospital
state: Guangdong
city: Guilin
country: China
facility: Affiliated Hospital of Guilin Medical University
state: Guangxi
city: Handan
country: China
facility: Affiliated Hospital of Hebei Engineering University
state: Hebei
city: Shijiazhuang
country: China
facility: The Forth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The second affiliated hospital of harbin medical university
state: Heilongjiang
city: Anyang
country: China
facility: Puyang District Hospital of Anyang City
state: Henan
city: Nanyang
country: China
facility: The First People's Hospital of Nanyang
state: Henan
city: Zhengzhou
country: China
facility: People's Hospital of Henan province
state: Henan
city: Shiyan
country: China
facility: Shiyan Renmin Hospital
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The third xiangya hospital of central south university
state: Hunan
city: Nanjing
country: China
facility: Qian-jin Lu
state: Jiangsu
city: Jiujiang
country: China
facility: Affiliated Hospital of Jiujiang University
state: Jiangxi
city: Changchun
country: China
facility: The Second Hospital of Jilin University
state: Jilin
city: Panjin
country: China
facility: Panjin Liaoyou Gem Flower Hospital
state: Liaoning
city: Shenyang
country: China
facility: The First Affiliated Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: Air Force Medical University
state: Shaanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shaanxi
city: Dongying
country: China
facility: Shengli Oil Field Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong First Medical University Affiliated Dermatology Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Qingdao
country: China
facility: The Affiliated Hospital Of Qingdao University
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital Affiliated to Fudan University
state: Shanghai
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 Uygur Autonomous Region
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Wenling
country: China
facility: The First People's Hospital of Wenling
state: Zhejiang
Study officials:
References: