Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Telitacicept in Moderately to Severely Active Systemic Lupus Erythematosus Patients
- Trial ID
- 2024-512716-21-00
- Protocol
- RC18G002
- Sponsor
- Remegen Co. Ltd.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** of telitacicept at Week 52 in adult patients with moderately to severely active Systemic Lupus Erythematosus (SLE) who have shown an inadequate response to standard of care (SoC) therapy. This is clinically relevant as it aims to provide an alternative treatment option for patients who do not respond sufficiently to existing therapies, potentially improving disease management and patient outcomes.
Secondary objectives include:
- Evaluating the efficacy of telitacicept at Week 24 in the same patient population.
- Assessing the glucocorticoid (GC) sparing effect of telitacicept when added to SoC therapy.
- Evaluating both the GC sparing effect and improvement in disease activity with telitacicept addition.
- Measuring efficacy through at least partial improvement in all organ systems active at baseline.
- Assessing the reduction in SLE flares with telitacicept addition.
- Evaluating clinically meaningful improvement in patient-reported outcomes (PROs).
- Assessing the safety of telitacicept in the target patient population.
Participants
The clinical trial involves a total of **287 participants** diagnosed with **Moderately to Severely Active Systemic Lupus Erythematosus** (SLE). The study population includes both male and female subjects, with an age range of 12 to 70 years. Participants were selected based on their inadequate response to standard of care therapy for SLE. The trial includes both adults and adolescents, although subjects under 18 years are not included in the primary analysis. Participants are required to have a stable health status, with a weight of at least 35 kg, and must meet specific diagnostic criteria for SLE, including a SELENA-SLEDAI total score of 6 or more. Lifestyle considerations such as adherence to effective contraception methods and abstaining from donating blood, sperm, or eggs are mandatory. Participants must also be appropriately vaccinated according to local guidelines. The trial population includes a vulnerable group, as it involves individuals with a chronic autoimmune condition.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, Phase 3 study to evaluate the efficacy and safety of **telitacicept** in patients with moderately to severely active **systemic lupus erythematosus** (SLE). The trial aims to assess the efficacy of telitacicept at Week 52 in adult patients who have shown an inadequate response to standard of care (SoC) therapy. The study will involve the administration of telitacicept via **subcutaneous injection** using a solution in a pre-filled syringe, with a maximum daily dose of 160 mg and a total dose not exceeding 8320 mg over a 52-week period.
Participants will be involved in the study for a duration of 52 weeks, with the trial estimated to conclude by August 2027. The sequence of study visits includes an initial screening visit to confirm eligibility based on inclusion criteria such as age, weight, and SLE diagnosis, followed by a baseline visit on Day 0 where the first dose of the study medication is administered. Subsequent follow-up visits will occur at regular intervals to monitor the participants' response to the treatment, assess any adverse events, and ensure compliance with the study protocol. The end-of-study visit will take place at Week 52, where the primary endpoint, the proportion of patients achieving an SLE Responder Index (SRI-4) response, will be evaluated.
Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for the participant's safety. The study will also monitor secondary endpoints, including the proportion of patients achieving an SRI-4 response at Week 24, glucocorticoid dose reduction, and time to flare, among others. The trial will ensure that all participants adhere to effective birth control methods and abstain from donating blood, sperm, or eggs during the study and for at least four months after the last dose of the study medication.
Treatment
The clinical trial involves the administration of **Telitacicept**, a protein-based experimental medication, formulated as a **solution for injection in a pre-filled syringe**. The active substance, telitacicept, is derived from a protein of other origin. The medication is administered via **subcutaneous injection**. The dosing regimen includes a maximum daily dose of 160 mg, with a total maximum dose of 8320 mg over a treatment period of 52 weeks. The pre-filled syringe device used for administration does not possess a CE mark. The trial aims to evaluate the efficacy and safety of telitacicept in patients with moderately to severely active **Systemic Lupus Erythematosus** (SLE) who have shown an inadequate response to standard-of-care therapy.
The study also includes a **matching placebo** for telitacicept, which serves as the comparator treatment in this double-blind, placebo-controlled trial. The placebo is designed to mimic the appearance and administration route of the telitacicept injection, ensuring blinding of both participants and investigators. The placebo does not contain any active pharmaceutical ingredients and is used to assess the efficacy of telitacicept by providing a baseline for comparison. The administration schedule and compliance monitoring for the placebo group are identical to those of the telitacicept group, ensuring consistency across the study arms.
Efficacy
The efficacy of Telitacicept in the treatment of moderately to severely active **Systemic Lupus Erythematosus** (SLE) will be assessed through a series of predefined endpoints in a Phase 3 clinical trial. The primary endpoint is the proportion of patients achieving an SLE Responder Index (SRI-4) response at Week 52. Secondary endpoints include the proportion of patients achieving an SRI-4 response at Week 24, and among those on a baseline glucocorticoid (GC) dose of more than 7.5 mg/day prednisone or equivalent, the proportion achieving a GC dose reduction of at least 25% to 7.5 mg/day or less by Week 40 and maintaining that dose through Week 52. Additionally, the trial will evaluate the proportion of patients achieving an SRI-4 response at Week 52 while maintaining an average daily dose of 7.5 mg prednisone or equivalent between Week 40 and Week 52, and the proportion achieving a BILAG-based Combined Lupus Assessment (BICLA) response at Week 52.
Other efficacy assessments include the time to flare as assessed by the SLE Flare Index (SFI) from baseline through Week 52, and the proportion of patients achieving clinically meaningful improvement in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at Week 52. The trial will also monitor the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI), as well as AEs leading to patient discontinuation of study medication. Changes from baseline in vital sign parameters and clinical laboratory assessments will be evaluated by visit. These efficacy parameters will be measured and collected at specified timepoints throughout the trial, ensuring a comprehensive evaluation of Telitacicept's therapeutic impact on SLE.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Adult patients (18-70 years old) who are able to understand and willing to sign the ICF and comply with study procedures as defined in the protocol. Adolescent patients (12-17 years old) who are able to sign an age-appropriate assent with a legal guardian who can understand and voluntarily sign an informed consent.
- Age 12-70 years at screening. a. Enrolling subjects under the age of 18 is optional and only applicable for sites that have EC approval. b. Subjects under the age of 18 will not be included in the primary analysis.
- Weight ≥35 kg at screening and at Day 0.
- Has had a diagnosis of SLE for at least 6 months prior to the Screening Visit.
- Meets the 2019 EULAR/ACR Classification criteria for SLE.
- Meets qualification standards as assessed by a CRC which include: a. Convincing diagnosis of SLE. b. Evidence of acute SLE disease that justifies the scoring on disease activity instruments and entry into a clinical trial of an investigational drug. c. Sufficient medical stability to enter the protocol without undue risk.
- Moderate to severely active SLE is defined by the following: a. SELENA-SLEDAI total score ≥ 6 points with clinical SLEDAI score ≥4 points (excluding points attributed to CNS manifestations) at screening. i. The clinical SLEDAI is the score without the inclusion of points attributable to any laboratory results (i.e., hematology, renal or immunologic measures) b. BILAG-2004 organ system scores of at least 1A or 2 B at screening.
- Clinical SLEDAI score of ≥ 4 at Day 0 prior to randomization (excluding points attributed to CNS manifestations) and no “definite” improvement or “major or complete” improvement in SLE disease activity during screening period based on Clinician’s Global Impression of Change (CGIC).
- Positive ANA ≥1:160 by immunofluorescent assay at the central laboratory, and/or positive anti-dsDNA antibodies, and/or positive anti-Sm antibodies. If a patient tests negative for ANA, anti-dsDNA, and anti-Sm antibodies, but positive for other autoantibodies (e.g., anti-SSA/Ro antibodies) or low complements, the eligibility will be reviewed and determined by the CRC based on the patient’s disease activity and other relevant criteria. All tests are required to be evaluated at the central laboratory and borderline results are considered negative. The serological parameter testing may be repeated once at the central laboratory during the screening period for consideration of eligibility.
- Currently receiving at least one of the following SoC SLE therapies: a. Oral GCs, if taken, the following criteria must be met: i. Must have been on an average daily dose of ≤20 mg/day prednisone or equivalent for ≥2 weeks prior to screening. ii. Must have been on a stable dose of oral GCs for ≥4 weeks prior to Day 0 (first dose of study medication). No dose adjustment during screening period is permitted. iii. If the oral GC is the only SoC therapy (i.e., the patient is not concurrently receiving any antimalarial or immunosuppressant), a dose of >7.5 mg/day but ≤ 20 mg/day of prednisone or equivalent is required. b. Antimalarial (≤250mg/day chloroquine, ≤400mg/day hydroxychloroquine): administered for a minimum of 12 weeks before screening and at a stable dose for ≥6 weeks prior to Day 0 (first dose of study medication). c. Immunosuppressants: administered for a minimum of 12 weeks before screening and at a stable dose for at least 6 weeks prior to Day 0 (first dose of study medication). The allowable immunosuppressants (no more than 1) and maximum allowable dosages are included below: o azathioprine (oral) ≤ 200 mg/day or 6 mercaptopurine ≤ 100 mg/day o mizoribine (oral) ≤ 150 mg/day o methotrexate (oral, subcutaneous, or IM) ≤ 25 mg/week o mycophenolate mofetil (oral) ≤ 2 grams/day or mycophenolic acid (oral) ≤ 1.44 grams/day o leflunomide (oral) ≤ 20 mg/day o tacrolimus (oral) ≤ 5 mg/day in divided doses o voclosporin (oral) ≤ 47.4 mg/day in divided doses o cyclosporine (oral) ≤ 4 mg/kg/day in divided doses d. If an immunosuppressant or antimalarial agent is discontinued prior to screening, the last dose must be at least 4 weeks prior to screening.
- Women of childbearing potential (WOCBP) must use highly effective methods of contraception (Refer to Appendix 10.4.2) throughout their study participation and for at least 4 months following the last administration of the study medication. For all WOCBP patients, a negative serum pregnancy test must be documented at screening. In addition, a negative urine (dipstick) pregnancy test must be documented at baseline (Day 0) prior to the first dose of the study medication. [For purposes of this study, ‘non-childbearing’ potential is defined as a premenarcheal female who has not yet entered puberty as evidenced by lack of breast development (palpable glandular breast tissue); or any female who has undergone a hysterectomy, S/P bilateral oophorectomy or tubal ligation, or is post-menopausal.] Female refers to the gender assigned at birth.
- Non-sterilized males who are sexually active with a female partner of childbearing potential must agree to adhere to the same effective birth control methods, from Day 0 through at least 4 months after receipt of the final dose of the study medication.
- All patients must agree to abstain from donating blood, sperm or eggs while on the study medication and at least 4 months after the last dose.
- Appropriately vaccinated (e.g., vaccinations for pneumococcus, influenza, and COVID-19) per investigator’s clinical judgment considering patient’s risk factors and according to country and local guidelines.
Exclusion Criteria
- Active lupus nephritis undergoing induction therapy or unstable renal diseases (e.g., levels of proteinuria, serum creatinine or active urinary sediment consistent with active nephritis that cannot be confirmed to be stable) within 12 weeks prior to screening, that in the opinion of the investigator or the CRC the patient would be unsuitable to enter a placebo controlled clinical trial.
- Active severe or unstable neuropsychiatric SLE, including but not limited to poorly controlled seizure, psychosis or acute confusional state, cerebrovascular accident, demyelination syndrome, cranial neuropathy, or evidence of active central nervous system vasculitis within 12 weeks of the screening visit.
- Have a primary diagnosis of a different autoimmune or inflammatory disorder that, in the opinion of the investigator or CRC, could confound SLE disease activity measures. Examples might include psoriasis, psoriatic arthritis, Lyme disease or multiple sclerosis.
- History of arterial or venous thromboembolism or microangiopathy within 12 months prior to screening. Patients with history of antiphospholipid syndrome who have had no thromboembolic event for at least 12 months and are on stable doses of therapeutic anticoagulation for at least one month prior to screening may be qualified at the discretion of the CRC. History of positive antiphospholipid antibodies with no associated clinical events is allowed.
- History of any non-SLE disease that has required treatment with oral or parenteral GCs for more than a total of 2 weeks within the last 24 weeks prior to screening.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Croatia | Not Yet Recruiting | 10 Jan 2025 | 9 |
 France | Not Yet Recruiting | 10 Jan 2025 | 9 |
 Greece | Not Yet Recruiting | 10 Jan 2025 | 9 |
 Italy | Not Yet Recruiting | 10 Jan 2025 | 9 |
 Poland | Not Yet Recruiting | 10 Jan 2025 | 12 |
 Romania | Not Yet Recruiting | 10 Jan 2025 | 15 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Telitacicept injection | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS INJECTION | 160 | 52 | PRD11285175 |
Matching placebo for Telitacicept | Placebo | N/A | — | — | — | N/A |