Efficacy and Safety Evaluation of Obexelimab in Systemic Lupus Erythematosus: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-510584-37-00
- Protocol
- ZB012-02-001
- Sponsor
- Zenas Biopharma (USA) LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this Phase 2, multicenter, randomized, double-blind, placebo-controlled study is to evaluate the **efficacy** of obexelimab compared to placebo in reducing disease activity in patients with **Systemic Lupus Erythematosus** (SLE). This is clinically relevant as SLE is a chronic autoimmune disease characterized by periods of increased disease activity, which can lead to significant morbidity. Reducing disease activity is crucial for improving patient outcomes and quality of life.
Secondary objectives include evaluating the efficacy of obexelimab compared with placebo to:
- Reduce SLE disease activity, achieve low disease activity, and prevent flare-ups.
- Achieve and maintain a low corticosteroid dose.
- Reduce fatigue.
Participants
The clinical trial involves a total of **111 participants** diagnosed with **Systemic Lupus Erythematosus** (SLE). The study population includes both male and female subjects, aged between 18 and 70 years. Participants were selected based on their ability to provide informed consent and their diagnosis of SLE at least 24 weeks prior to screening, meeting the 2019 EULAR/ACR classification criteria. The trial includes individuals with active disease, as indicated by specific clinical and laboratory criteria, and those receiving stable doses of standard nonbiologic lupus therapies such as oral corticosteroids, antimalarials, or immunosuppressants. Lifestyle considerations include the requirement for stable medication regimens and adherence to contraceptive measures for both male and female participants. The trial population is considered vulnerable, reflecting the careful selection process to ensure the safety and efficacy of the investigational treatment.
Plans and Procedures
The clinical trial is a **Phase 2**, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the efficacy and safety of **Obexelimab** in patients with **Systemic Lupus Erythematosus** (SLE). The primary objective is to assess the efficacy of Obexelimab compared to placebo in reducing SLE disease activity. The trial is expected to commence recruitment on October 1, 2024, and conclude by March 31, 2026. Participants will be randomly assigned to receive either Obexelimab, a placebo, or a comparator treatment, with the study drug administered via subcutaneous injection.
The trial will involve several study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as age, diagnosis, and disease activity. Participants must be between 18 and 70 years old, have a confirmed diagnosis of SLE, and meet the 2019 EULAR/ACR classification criteria. The screening visit will also ensure that participants are on stable doses of background nonbiologic lupus standard of care therapies. Following the screening, participants will attend regular follow-up visits to monitor their response to treatment and any adverse events. The primary endpoint is the proportion of patients achieving a response at Week 24, as defined by the BILAG-Based Composite Lupus Assessment (BICLA) Response. Secondary endpoints include the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) and other measures of disease activity and quality of life.
The expected duration of participant involvement is up to 24 weeks, with the possibility of early termination if specific conditions arise, such as significant adverse events or lack of compliance with the study protocol. Participants will be required to attend an end-of-study visit to assess the final outcomes and ensure their well-being post-trial. The study is designed to maintain rigorous scientific standards, ensuring that the data collected will contribute valuable insights into the treatment of SLE with Obexelimab.
Treatment
The clinical trial involves the administration of **Obexelimab**, an experimental medication, to evaluate its efficacy and safety in patients with **Systemic Lupus Erythematosus**. Obexelimab is provided in the form of an injection and is administered via **subcutaneous injection**. The maximum daily dose of Obexelimab is 250 mg, with a total maximum dose of 6000 mg over a treatment period of up to 24 weeks. The active substance in Obexelimab is a protein of other origin, specifically designed for this study. The medication is not a pediatric formulation and has been designated as an orphan drug under the number EU/3/17/1962.
In addition to the experimental treatment, the study includes the use of **Prednisolone**, a non-experimental treatment with anti-inflammatory properties similar to other corticosteroids. Prednisolone is administered orally, with a maximum daily dose of 20 mg and a total maximum dose of 20 mg over a treatment period of up to 12 weeks. The active substance in Prednisolone is **Betamethasone Sodium Phosphate**, a chemical compound commonly used in clinical settings for its therapeutic effects.
The study also incorporates a **placebo** control, which is a sterile solution for subcutaneous injection. The placebo is used to maintain the double-blind nature of the trial, ensuring that neither the participants nor the investigators are aware of the treatment assignments. This approach is critical for accurately assessing the efficacy and safety of Obexelimab compared to the placebo.
Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial is conducted in a randomized, double-blind, placebo-controlled manner to provide robust and reliable data on the potential benefits and risks associated with Obexelimab in the treatment of Systemic Lupus Erythematosus.
Efficacy
The efficacy of Obexelimab in patients with **Systemic Lupus Erythematosus** will be assessed through a series of predefined endpoints. The primary endpoint is the proportion of patients who achieve a response at Week 24, as defined by the BILAG-Based Composite Lupus Assessment (BICLA) Response. Secondary endpoints include the proportion of patients achieving a response according to the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 24, the proportion of patients reaching Lupus Low Disease Activity State (LLDAS) at Week 24, and the time to flare. Additional secondary endpoints involve the proportion of patients achieving a prednisone equivalent dose of ≤ 5 mg/day by Week 12 and maintained through Week 24 without disease worsening, a ≥ 50% improvement from baseline in the Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score (CLASI-50 response) at Week 24, and a ≥ 50% decrease in active joint count (Joint-50 response) at Week 24 compared with baseline. Furthermore, changes from baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 24 will also be evaluated.
Inclusion and Exclusion Criteria
Inclusion Criteria
- ≥ 18 to ≤ 70 years of age.
- Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.
- Diagnosed with SLE at least 24 weeks prior to screening and meets the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria.
- At screening, at least one of the following: a) anti-nuclear antibody (ANA) ≥ 1:80 b) positive anti-dsDNA c) positive anti-Sm
- Patient has all 3 of the following based on features active on the day of the visits: a) hSLEDAI ≥ 6 and clinical hSLEDAI ≥ 4 at screening, and clinical hSLEDAI ≥ 4 at Day 1. Note: Clinical points exclude laboratory tests, except proteinuria. Patients with proteinuria scored as present (i.e., urine protein/creatinine > 500 mg/g) at screening will also be scored as present on Day 1 if a dipstick performed at the site on Day 1 is at least 2+ proteinuria. If the urine protein/creatinine > 500 mg/g at screening is not known to be stable based on recent past proteinuria testing, then a repeat urine protein/creatinine measurement is required during the Screening Period. b) BILAG-2004 Grade A or B in ≥ 1 organ system at screening and Day 1. c) In the opinion of the investigator and the central adjudicator, there is sufficient disease activity to warrant enrollment into a clinical study with an investigational agent.
- Patients must be treated with one or more of the following background nonbiologic lupus standard of care therapies: oral corticosteroid, antimalarial, and/or immunosuppressant. The treatment regimen must be as below: a) If taking oral corticosteroid: No increase in dosing regimen during the Screening Period, and at stable dose ≤ 20 mg/day prednisone-equivalent at least 2 weeks prior to Day 1. b) If taking antimalarial: - No dose increase within 8 weeks prior to the Screening visit. - After the Screening visit (i.e., during the Screening Period and the Treatment Period), dosing must be stable and as follows: hydroxychloroquine ≤ 400 mg/day, quinacrine ≤ 100 mg/day, or chloroquine ≤ 250 mg/day. c) If taking immunosuppressant: - No dose increase within 8 weeks prior to the Screening visit. - After the Screening visit (i.e., during the Screening period and the Treatment period), must be taking no more than 1 immunosuppressant and at a stable dose as follows: mycophenolate mofetil ≤ 3 g/day, mycophenolate sodium ≤ 2160 mg/day, azathioprine ≤ 200 mg/day, 6- mercaptopurine ≤ 100 mg/day, methotrexate ≤ 25 mg/week, cyclosporine ≤ 2 mg/kg/day, tacrolimus ≤ 3 mg/day, or voclosporin ≤ 23.7 mg twice daily.
- Female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) Not a woman of childbearing potential (WOCBP) as defined in Appendix 5. OR b) A WOCBP who meets all of the following: - Agrees to either sexual abstinence or use of contraception (as detailed in Appendix 5) until at least 8 weeks after the last administration of IMP. - Has a negative serum pregnancy test at screening and a negative urine pregnancy test at Day 1 prior to the first dose of IMP. - Agrees to refrain from egg donation until at least 8 weeks after the last dose of IMP.
- A male patient is eligible if the following conditions apply: - Agrees to either sexual abstinence or use of contraception (as detailed in Appendix 5) until at least 8 weeks after the last dose of IMP or is surgically sterile. AND Agrees to refrain from donating sperm until at least 8 weeks after the last dose of IMP.
Exclusion Criteria
- Patients are excluded from the study if any of the following criteria apply: 1. Active lupus nephritis for which, in the opinion of the investigator or the central adjudicator, current medications are insufficient for patient’s safety or additional therapy that is not permitted in the protocol is needed.
- A history of thrombosis or embolism in the previous 6 months before the Screening visit, or thrombotic history in the previous 12 months associated with antiphospholipid syndrome (APS) or another relevant hypercoagulable state. A thrombotic history associated with APS or another relevant hypercoagulable state more than 12 months prior to Screening visit is excluded if it is not treated per local standards with prophylactic anticoagulation.
- Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE, such as, but not limited to, psoriasis, dermatomyositis, and systemic sclerosis.
- Active severe neuropsychiatric or CNS SLE.
- Current inflammatory disease other than SLE (including, but not limited to, rheumatoid arthritis, psoriatic arthritis, spondyloarthropathy, reactive arthritis, scleroderma, dermatomyositis) that may interfere with the assessment of lupus signs and symptoms in the opinion of the investigator or central adjudicator. Current diagnosis of thyroiditis or secondary Sjogren's Syndrome is permitted.
- Presence of uncontrolled or New York Heart Association Class III or IV congestive heart failure.
- Any condition or finding on physical exam, current or previous medical history, vital signs, 12-lead ECG, or laboratory tests that, in the opinion of the investigator or central adjudicator, might interfere with the evaluation of the investigational product or should otherwise exclude a patient.
- Surgery (not considered minor by the investigator or the central adjudicator) within 4 weeks before Screening, or planned surgery during the study.
- History of relevant allergies, including allergy to study drug or any murine or human-derived protein or immunoglobulin products that, in the opinion of the investigator or central adjudicator, make inclusion in the study inappropriate.
- Malignancy within 5 years except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin.
- History of drug or alcohol abuse in the previous 12 months before screening in the opinion of the investigator.
- Use prior to screening of one or more of the following: a) Within 6 months: rituximab or similar major B cell-depleting biologic therapy, or T cell-depleting agent such as Campath (alemtuzumab). Note: Patients who received B-cell-targeted therapy > 6 and ≤ 12 months prior to randomization must have a B-cell count that is within the laboratory reference range at screening, as measured by the central laboratory. b) Within 1 month: belimumab or any inhibitor of B cell activating factor (BAFF) and/or APRIL, anifrolumab, abatacept, infliximab, adalimumab, certolizumab, golimumab, etanercept, tocilizumab, anakinra, immunoglobulin, blood products, cyclophosphamide IV or oral, live or live-attenuated vaccine, or other biologics with immunomodulating/immunosuppressive activity. c) Within 5 half-lives or 30 days, whichever is longer: any investigational drug.
- Use after the Screening visit of medical treatment (including prescription drugs, non-prescription drugs, biological products, Chinese or herbal medicines, diet supplements, etc.) or health care products considered by the investigator or central adjudicator to potentially impact the interpretation of study results.
- Currently enrolled in another interventional clinical study. Note: Patients enrolled in ongoing cohort or non-interventional studies may not donate blood or tissue samples for such studies during their participation in this study (including the Follow-up Period). All the other exclusion criteria can be found in the protocol (section 5.2.2).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Oct 2024 | 6 |
 Bulgaria | Not Recruiting | 01 Oct 2024 | 9 |
 Denmark | Not Recruiting | 01 Oct 2024 | 6 |
 Germany | Not Recruiting | 01 Oct 2024 | 7 |
 Greece | Not Recruiting | 01 Oct 2024 | 10 |
 Italy | Not Recruiting | 01 Oct 2024 | 4 |
 Poland | Not Recruiting | 01 Oct 2024 | 31 |
 Portugal | Not Recruiting | 01 Oct 2024 | 5 |
 Romania | Not Recruiting | 01 Oct 2024 | 6 |
 Spain | Not Recruiting | 01 Oct 2024 | 7 |
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 |
|---|---|---|---|---|---|---|
PREDNISOLONE | Other | PHF00059MIG | ORAL | 20 | 12 | SCP107974752 |
Placebo sterile solution for SC injection | Placebo | N/A | — | — | — | N/A |
Obexelimab | Test | INJECTION | SUBCUTANEOUS INJECTION | 250 | 24 | PRD9993985 |