A Clinical Trial on the Efficacy and Safety of TQH3906 in the Treatment of Systemic Lupus Erythematosus

A Randomized, Double-blind, Placebo-controlled, Multi-center Phase II Clinical Trial Evaluating the Efficacy and Safety of TQH3906 in the Treatment of Systemic Lupus Erythematosus

To assess the efficacy and safety of TQH3906 in treating systemic lupus erythematosus.

Inclusion Criteria:

• Sign a written informed consent form, which must meet the following requirements:

  • Willingness to participate in the study and ability to sign an informed consent form.
  • Willingness and ability to complete all research-related procedures and site visits.

• Characteristics of participants in the Systemic Lupus Erythematosus (SLE) trial:

  • Screen for patients with a confirmed diagnosis of SLE dating back to at least 24 weeks prior to the visit.
  • Diagnosed with systemic lupus erythematosus according to the 2019 classification criteria of the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).
  • Meet one of the following criteria: elevated levels of antinuclear antibodies (ANA) ≥ 1:80, positive results for anti-double-stranded DNA (anti-dsDNA) (positive results include indeterminate results), or positive results for anti-Smith (anti-Sm) antibodies.
  • Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k) score ≥ 8 and clinical SLEDAI-2K score ≥ 4, with involvement of joints and/or skin vasculitis and/or rash manifestations (Note: Clinical SLEDAI-2K manifestations do not include complement deficiency and positivity for anti-ds-DNA antibodies).

• Age between 18 and 75 years old (based on the date of signing the informed consent form).

• Medications for SLE treatment:

  • Prior to the screening visit, there must be a period of background therapy of at least 12 weeks. The therapy must have been administered at a stable dose for at least 4 weeks prior to the screening visit and remain stable until randomization and throughout the duration of the study participation. If antimalarial or immunosuppressive therapy is discontinued prior to the screening visit, the last dose must have been administered at least 4 weeks prior. Detailed information on specific medications is as follows:

    1. Immunosuppressants (can be used only one type; combination use is not permitted): Antimalarial drugs: Hydroxychloroquine (allowed for monotherapy; allowed in combination with one type of immunosuppressant) (maximum 400 mg/day).
    2. Duration of clearance when using other immunomodulatory drugs or biologics.

  • Corticosteroids (CS) (prednisone or equivalent medication) is permitted but not required as background therapy. For trial participants using CS, the dose must be stable for at least 2 weeks prior to the screening visit, not exceed 40 mg/day during screening, and remain stable prior to randomization. Monotherapy with CS is not permitted.

  • The requirements for trial participants currently receiving long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) are as follows:

    1. The dosage must remain stable for a period of 14 days prior to the screening visit and must remain stable until randomization and throughout the study period. The use of NSAIDs alone is not permitted.
    2. A maximum of one oral NSAID (at a stable dosage) may be used during the study period.
    3. The concurrent use of aspirin as a cardiovascular protective agent/to prevent thrombosis (in addition to other NSAIDs) is permitted throughout the study period, provided that the dosage remains stable.

• Women of childbearing age must agree to use effective contraceptive measures during the study period and for 6 months thereafter, and undergo a blood pregnancy test that is negative within 7 days prior to enrollment in the study. Men must agree to use effective contraceptives during the study period and for the subsequent 6 months.

Exclusion Criteria:

• Conditions other than SLE:

  • drug-induced SLE;
  • Trial participants with other autoimmune diseases (e.g. multiple sclerosis, psoriasis, inflammatory bowel disease, etc.) were excluded. Test participants with secondary dry syndrome could not be excluded;
  • Excluded trial participants with overlapping syndromes of SLE, such as systemic sclerosis and mixed associative weaving disease;
  • In the case of a combination of antiphospholipid syndrome secondary to systemic lupus erythematosus, prior severe blood clots / obstetric complications need to be ruled out; Prophylaxis with low-dose aspirin (50-100 mg / d) in the absence of thrombotic events or obstetric comorbidities and with high-risk antiphospholipid antibody (aPL) characteristics may be included;
  • Trial participants who had had lupus encephalopathy before screening were excluded;
  • Excluding active, severe lupus nephritis requiring cytotoxic drugs (CTX) or high-dose CS treatment, excluding lupus pinocytosis, thrombotic microangiopathy; Trial participants with lupus nephritis, but who are currently controlled, may be included;

• Other medical conditions and medical history;

  • Study participants who are pregnant or breastfeeding;
  • Evidence of a significant disease / condition or unstable clinical condition (e.g. kidney, Liver, blood, gastrointestinal, endocrine, lung, immune, psychiatric) or locally active infection / infectious disease which, according to medical judgement, will significantly increase the risk of the trial participants if they participate in the study;
  • Have had any major surgery within 30 days prior to the first dose of the study treatment, or planned to have any surgery during the course of the study;
  • Cancer or a history of cancer or lymphotrophic disease within the past 5 years (except adequately treated basal cell carcinoma or squamous cell carcinoma with no evidence of recurrence);
  • Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA) or any recent episode of heart failure resulting in symptoms of NYHA Class III / IV; Or a history of clinically significant ventricular arrhythmia (e.g. persistent ventricular arrythmia , ventricular tremor, sharp twisted ventricular articular arrhythmia) or an arrhythmia that requires continuous anti-arrhythmic medication;
  • A history of acute coronary syndrome (e.g. myocardial infarction, unstable angina) and / or any major cerebrovascular disease within 24 weeks prior to screening;
  • Currently or recently (within 3 months prior to randomization) had a gastrointestinal disease, including gastrointestinal surgery, that was likely to affect treatment absorption in the study;
  • In medical judgment, the trial participants had non-SLE concomitant conditions that may require additional systemic corticosteroid therapy during the study (e.g., asthma);
  • Severe blood loss (> 500 mL) or transfusion within 4 weeks prior to randomization;
  • It is not possible to take the drugs orally;
  • Unable to receive venous punctures and / or tolerate venous pathways;
  • Persons who have a history of substance abuse and cannot quit or who have psychiatric disorders;
  • Any other medical, spiritual and / or social reasons determined by medical judgement;

• Previous and combined drug use:

  • Unable to adhere to restricted and prohibited treatments; Unable to comply with the discontinuation requirement;
  • Use more than one immunosuppressant;
  • Previous exposure to other TYK2 inhibitors;
  • Participants who were previously exposed to anti-interferon targeted drug trials such as Anilumab, Rontalizumab, nterferon Alpha Kinoid (INFaKinoid), etc.;
  • Other research drugs must be discontinued for at least 12 weeks or 5 half-lives (whichever is longer) before screening.

• Infection Related:

  • Chest radiology within 6 months prior to screening showed the presence of active Tuberculosis (TB) in the trial participants. Test participants who were negative for chest radiology within 3 months prior to screening were eligible to participate in the study:
  • Hepatitis C, hepatitis B, or human immunodeficiency virus (HIV) infection, characterized by antibodies to hepatitis C (anti-HCV) and all HCV-RNA positive, surface antigens to hepatitis B (HBsAg) positive, core antibodies to the hepatitis A (HBcAb) and all HIV-DNA positive, or HIV antibody screening positive;
  • is currently receiving any treatment regarding chronic infections;
  • Persons in need of treatment for syphilis;
  • Have a congenital or acquired immunodeficiency disorder;
  • Have a history of repeated infections requiring hospitalization or treatment outside the bowel (muscle or intravenous) and receiving intravenous antibiotics; Or need to be hospitalized and / or given intravenous anti-infective treatment within 30 days of the random, or receive any infection requiring oral anti-infectious treatment within 14 weeks of the random;
  • Prior history of systemic shingles; Or have two or more recurrent shingles in two years; Or the shingles infection did not completely subside within 12 weeks prior to screening;
  • Vaccinated live within 90 days of randomization or inactivated within 30 days of randomisation;

• Abnormalities in physical or laboratory tests:

  • Clinically significant chest X-ray or ECG abnormalities
  • A laboratory test of clinical significance is abnormal. A screening period laboratory test with abnormal results may be repeated once to confirm abnormal results. If the results are restored to programme acceptable during the screening period without intervention, trial participants may be admitted to the study;
  • Any other significant laboratory abnormalities that may, in medical judgement, pose an unacceptable risk to the trial participants during the study period;

• Other exclusion criteria:

  • Have a history of any significant drug allergy (e.g. causing an allergic reaction or causing liver toxicity); He is known to be allergic to the ingredients of research drugs;
  • those who are unable to comply with the pilot programme;
  • Persons who are ready to undergo or have previously undergone a heterotopic bone marrow transplant or a solid organ transplant;
  • In the judgement of the investigator, there is a situation that seriously endangers the safety of the test participants or affects the completion of the study by the test participant.