Metformin Combined With Secukinumab for Moderate-to-Severe Plaque Psoriasis in Overweight or Obese Chinese Patients

Официальное название

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Metformin in Combination With Secukinumab for the Treatment of Moderate-to-Severe Plaque Psoriasis in Overweight or Obese Chinese Patients

Обзор

This is a randomized, double-blind, placebo-controlled, multicenter clinical trial conducted in China. The study aims to evaluate the efficacy and safety of metformin combined with secukinumab in the treatment of moderate-to-severe plaque psoriasis in overweight or obese Chinese patients. A total of approximately 186 participants will be enrolled and randomly assigned in a 1:1 ratio to receive either secukinumab plus metformin or secukinumab plus placebo. The study consists of a screening period, an induction period, a maintenance period, and a follow-up period, with a total duration of 60 weeks. The primary endpoints are the proportions of participants achieving PASI75 (≥75% improvement in Psoriasis Area and Severity Index) and an IGA score of 0 or 1 (clear or almost clear) at Week 24. Secondary endpoints include PASI90, quality of life (DLQI), pruritus NRS score, metabolic parameters, and safety assessments. This study aims to provide a more effective combination therapy for psoriasis patients with overweight or obesity.

Вмешательства

• Препарат Secukinumab 300mg s.c.
  Secukinumab is a fully human monoclonal antibody that selectively targets interleukin-17A (IL-17A), a key cytokine involved in the pathogenesis of psoriasis. In this study, secukinumab is administered as a subcutaneous injection at a dose of 300 mg. The dosing schedule includes weekly injections during the induction period (Weeks 0, 1, 2, 3, and 4), followed by maintenance dosing every 4 weeks thereafter. It is used in both the experimental and control arms.
• Препарат Metformin
  Oral biguanide medication. Starting dose: 500 mg/day, titrated weekly by 500 mg to a maximum of 2000 mg/day (or maximum tolerated dose, e.g., 1500 mg/day), then maintained.
• Препарат Placebo
  Placebo tablets matching metformin in appearance, administered orally following the same titration schedule.

Первичные конечные точки

• Proportion of Participants Achieving PASI75 at Week 24 [Срок оценки: Baseline to Week 24]
• Proportion of Participants Achieving IGA Score of 0 or 1 at Week 24 [Срок оценки: Baseline to Week 24]

Вторичные конечные точки (8)

• Proportion of Participants Achieving PASI90 at Week 24 [Срок оценки: Baseline to Week 24]
• Proportion of Participants Achieving PASI75/90/100 at Week 52 [Срок оценки: Baseline to Week 52]
• Proportion of Participants Achieving IGA 0/1 at Week 52 [Срок оценки: Baseline to Week 52]
• Change in DLQI Score at Week 24 [Срок оценки: Baseline to Week 24]
• Proportion of Participants with DLQI Score of 0 or 1 at Week 24 [Срок оценки: Baseline to Week 24]
• Change in Pruritus NRS Score at Week 24 [Срок оценки: Baseline to Week 24]
• Proportion of Participants with ≥2.5% Weight Loss at Week 24 [Срок оценки: Baseline to Week 24]
• Proportion of Participants Achieving PASI75/90/100 at Week 52 Among Those Who Achieved PASI50 but Not PASI75 at Week 24 [Срок оценки: Week 24 to Week 52]

Критерии участия

Критерии включения

• Subjects voluntarily participate in the study and sign the informed consent form.
• Aged 18-75 years (inclusive) at the time of signing informed consent, male or female.
• Diagnosed with chronic plaque psoriasis for >=6 months prior to the first study drug administration.
• Overweight/obesity: Body mass index (BMI) >=25 kg/m².
• Moderate-to-severe plaque psoriasis (defined as):

Psoriasis Area and Severity Index (PASI) score >=12 at screening and prior to first dose.

Investigator's Global Assessment (IGA) score >=3 at screening and prior to first dose.

Stable disease within 2 months prior to randomization.

• Deemed candidates for phototherapy or systemic therapy by the investigator, defined as subjects with moderate-to-severe chronic plaque psoriasis uncontrolled by:

Topical therapy and/or phototherapy and/or prior systemic therapy.

• Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study medication (Day 0). Both women of childbearing potential and male patients with reproductive capacity must agree to use highly effective contraceptive methods during the study and for 15 weeks following the last dose.
• Lactating women agree to discontinue breastfeeding during the study and for 15 weeks following the last dose of study medication.
• Subjects must be capable of effective communication with investigators and adhere to the clinical trial protocol to complete all study requirements. -

Критерии исключения

• 1: BMI <25 kg/m². 2: Presence of guttate, pustular, or erythrodermic psoriasis, or other diseases that may confound treatment outcomes (e.g., cutaneous lesions, systemic autoimmune diseases).

3: Drug-induced psoriasis (e.g., new-onset or exacerbated psoriasis caused by beta-blockers, calcium channel blockers, or lithium).

4: Use of prohibited medications: Systemic non-biologic agents (e.g., glucocorticoids, leflunomide, methotrexate, cyclosporine, retinoids, azathioprine, mycophenolate mofetil, traditional Chinese medicines for psoriasis) within 4 weeks prior to screening.

Etanercept or its biosimilars within 4 weeks prior to screening; TNF-α inhibitors or their biosimilars within 12 weeks prior to screening.

Other biologic agents for psoriasis (e.g., IL-12/23 or IL-23 inhibitors) within 5 half-lives of the drug prior to screening.

5: Prior use of secukinumab or other IL-17A/IL-17R-targeted biologic agents within 12 weeks prior to screening.

6: History of malignancy within the past 5 years (e.g., cutaneous squamous cell carcinoma, basal cell carcinoma, cervical carcinoma in situ).

7: Active inflammatory diseases other than psoriasis that may confound the evaluation of secukinumab efficacy.

8: Metabolic or inflammatory diseases (e.g., type 2 diabetes) that may confound the evaluation of metformin efficacy.

9: History of lymphoproliferative disorders (e.g., lymphoma, lymphadenopathy) or splenomegaly.

10: Opportunistic infections within 6 months prior to screening (e.g., herpes zoster, CMV, Mycoplasma, Pneumocystis jirovecii, histoplasmosis, candidiasis, aspergillosis, NTM).

11: Chronic or recurrent infectious diseases (e.g., chronic hepatitis, pyelonephritis) or severe/life-threatening infections within 6 months prior to screening; current signs/symptoms suggestive of infection (e.g., fever, cough, dysuria, abdominal pain, diarrhea, infected skin wounds).

12: High risk of infection (e.g., leg ulcers, indwelling urinary catheters, recurrent chest infections, bedridden/wheelchair-bound status).

13: Major surgery within 8 weeks prior to screening or planned during the study, deemed to pose unacceptable risk by the investigator.

14: Live virus/bacterial vaccines (e.g., BCG) within 6 weeks prior to screening or planned during the study/within 15 weeks after last dose.

15: Participation in another clinical trial within 4 weeks prior to screening or within 5 half-lives of the investigational product (whichever is longer).

16: Laboratory abnormalities: Hemoglobin <8.5 g/dL WBC <2,500/μL ANC <1,500/μL Platelets <100,000/μL ALT/AST >2×ULN Creatinine >176.8 μmol/L (2.0 mg/dL) 17: Active hepatitis B (positive HBsAg). 18: Positive HCV antibody. 19: HIV infection or positive HIV antibody. 20: Syphilis infection. 21: Active or latent tuberculosis at screening. 22: Hypersensitivity to trial drug excipients, murine/human proteins, or immunoglobulin products.

23: Inability to communicate/comply (e.g., psychiatric disorders, frequent travel, lack of motivation).

24: Other conditions deemed by the investigator to compromise study participation.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT07485764 · 2025Lunshenzi(0610-03)

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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