A Multicentre, Randomised, Double-blind, Positive-control Clinical Trial Evaluating Dihydroartemisinin Tablets for the Treatment of Discoid Lupus Erythematosus

Overview

This study is a multicentre, randomised, double-blind, double-dummy, phase II clinical trial with a positive-control group, designed to evaluate the efficacy and safety of dihydroartemisinin tablets in the treatment of discoid lupus erythematosus (DLE).

Detailed description

Participants are screened during the screening phase, and those meeting the inclusion criteria are enrolled in the study. Enrolled participants were randomised in a 2:2:1 ratio to Treatment Group 1 (dihydroartemisinin 40 mg, twice daily), Treatment Group 2 (dihydroartemisinin 60 mg, twice daily) or the control group (hydroxychloroquine 200 mg, once daily). Participants in all groups will receive treatment for 24 weeks, during which efficacy and safety will be monitored at regular intervals.

Interventions

• Drug Dihydroartemisinin tablets
  Dihydroartemisinin 40mg, taken orally twice a day, for a treatment period of 24 weeks.
• Drug Dihydroartemisinin tablets
  Dihydroartemisinin 60mg, taken orally twice a day, for a treatment period of 24 weeks.
• Drug Hydroxychloroquine tablets
  Hydroxychloroquine 200mg, taken orally once a day, for a treatment period of 24 weeks.

Primary outcome measures

• Percentage change from baseline in the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI-A) score at week 24 [Time frame: Week 24]

Secondary outcome measures (9)

• Percentage change from baseline in the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI-A) score at weeks 2, 4, 8, 12, 16 and 20 [Time frame: weeks 2, 4, 8, 12, 16 and 20]
• Change in CLASI-A score from baseline [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Percentage of participants with a ≥50% reduction in CLASI-A score from baseline (CLASI-50) [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Percentage of participants with a ≥20% reduction in CLASI-A score from baseline [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Percentage of participants with a 4-point reduction in CLASI-A activity score from baseline [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Percentage of participants achieving a complete response (CR) in CLASI-A (defined as a score of '0') [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Proportion of participants with a post-treatment DLQI (Dermatology Life Quality Index) score reduced by 2 points or more compared to baseline [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Mean change in post-treatment DLQI (Dermatology Life Quality Index) score compared to baseline [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]
• Mean change in post-treatment PGA (Physician Global Assessment) score compared to baseline [Time frame: weeks 2, 4, 8, 12, 16, 20 and 24]

Eligibility criteria

Inclusion criteria

• Participants are able to understand the purpose and risks of the study and voluntarily sign an informed consent form;
• Aged between 18 and 65 years (inclusive);
• Body weight ≥ 45 kg;
• Diagnosed with discoid lupus erythematosus (DLE) at the screening visit (refer to the '2021 Guidelines for the Diagnosis, Treatment and Long-term Management of Cutaneous Lupus Erythematosus'); new patients must undergo a skin biopsy and provide a pathology report, whilst existing patients must provide a biopsy pathology report dated within the last 5 years;
• At the time of screening, the Cutaneous Lupus Erythematosus Area and Severity Index (CLASI-A) must be ≥4.

Exclusion criteria

• Patients with systemic lupus erythematosus (SLE) or those at high risk of developing SLE;
• Drug-induced lupus;
• Patients with a history of resistance to antimalarial treatment;
• At screening, aspartate transaminase (AST) or alanine transaminase (ALT) or gamma-glutamyltransferase (GGT) levels exceeding twice the upper limit of normal (ULN); or alkaline phosphatase (ALP) or total bilirubin levels exceeding 1.5 times the upper limit of normal (ULN); or serum creatinine (Cr) or urea (UREA) levels exceeding 1.5 times the upper limit of normal (ULN);
• Patients diagnosed with anaemia within 3 months prior to randomisation, or patients with haemoglobin levels below 110 g/L at screening;
• Patients who have used any antimalarial drug (hydroxychloroquine sulphate, chloroquine phosphate or chloroquine) within 4 weeks prior to randomisation;
• Patients who have used topical corticosteroids (e.g. mometasone furoate cream or others) or topical calcineurin inhibitors (e.g. tacrolimus ointment or others) within 2 weeks prior to randomisation;
• Patients treated with biologics (e.g. adalimumab, secukinumab or others) within 12 weeks prior to randomisation;
• Patients treated with immunomodulators (e.g. thalidomide, lenalidomide or others) within 4 weeks prior to randomisation;
• Patients who have received live vaccines (e.g. measles vaccine, varicella vaccine or others) within 4 weeks prior to randomisation;
• Patients who have used traditional Chinese medicinal preparations with lupus-modulating effects within 4 weeks prior to randomisation, such as Tripterygium preparations (e.g. Tripterygium glycosides), Paeonia lactiflora total glycosides capsules, Zhengqing Fengtongning, or Euphorbia root tablets;
• History of malignant tumours within the 5 years prior to screening;
• History of acute myocardial infarction, unstable angina, or severe arrhythmias (multifocal frequent premature ventricular contractions, ventricular tachycardia, ventricular fibrillation) within the 6 months prior to screening, or New York Heart Association (NYHA) Class III-IV;
• Conditions not effectively controlled at the time of screening or markedly unstable diseases (such as acute pneumonia, pulmonary arterial hypertension, diabetic ketoacidosis, acute pancreatitis, etc.), which, in the investigator's judgement, may confound the study results or expose the participant to undue risk;
• Patients with a history of major organ transplantation (e.g., heart, lung, kidney, liver) or haematopoietic stem cell and/or bone marrow transplantation within the 5 years prior to screening;
• A history of chronic, recurrent (three or more episodes of the same type of infection within 52 weeks) or recent severe infections (e.g. pneumonia, sepsis), including viral infections (particularly varicella and herpes zoster), or requiring anti-infective treatment during the screening period;
• Patients who have undergone any major surgery within 6 weeks prior to randomisation, such as abdominal, thoracic or joint replacement surgery, or who are scheduled to undergo major surgery during the study (including follow-up);
• Patients for whom the investigator, based on an ophthalmological examination prior to randomisation, considers the findings to be clinically significant and unsuitable for participation in this clinical trial, or who have diseases associated with retinal pathology;
• Pregnant or breastfeeding women, or women of childbearing potential who do not agree to use effective contraception during the clinical trial;
• Patients with known hypersensitivity to artemisinin-based drugs, hydroxychloroquine or excipients (lactose, microcrystalline cellulose, sodium carboxymethyl starch, sodium dodecyl sulphate, polyvinylpyrrolidone, magnesium stearate);
• Any other circumstances, as determined by the investigator, that may interfere with the assessment of efficacy.
• Individuals who abuse drugs or alcohol;
• Participants who have taken part in any clinical trial within the three months prior to screening (excluding those who underwent safety checks only and did not receive any substantive medication or therapeutic.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 10 centers

• The First Affiliated Hospital of Anhui Medical University — Hefei
• China-Japan Friendship Hospital — Beijing
• Peking University People's Hospital — Beijing
• The First Affiliated Hospital of Chongqing Medical University — Chongqing
• Nanfang Hospital, Southern Medical University — Guangzhou
• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou
• The Second Xiangya Hospital of Central South University — Changsha
• The First Affiliated Hospital of China Medical University — Shenyang
• … and 2 more centers

Identifiers

NCT: NCT07557927 · KPC078-C202

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗