A Phase 2 Study of Obexelimab in Patients with Systemic Lupus Erythematosus

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Zenas Biopharma (USA) LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

22 Oct 2024 → ongoing

Decision date (initial)

2024-10-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Zenas BioPharma (USA) LLC

External identifiers

EU CT number

2024-510584-37-00

WHO UTN

U1111-1302-2041

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Pharmacogenomic, Therapy, Pharmacodynamic

To evaluate the efficacy of obexelimab compared to placebo to reduce SLE disease activity.

Secondary objectives 1

1. To evaluate the efficacy of obexelimab compared with placebo to: • Reduce SLE disease activity, achieve low disease activity, and prevent flare • Achieve and maintain low corticosteroid dose • Reduce fatigue

Conditions and MedDRA coding

Systemic Lupus Erythematosus

Study design 3 periods

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. ≥ 18 to ≤ 70 years of age.
2. 2. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF.
3. 3. 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.
4. 4. At screening, at least one of the following: a) anti-nuclear antibody (ANA) ≥ 1:80 b) positive anti-dsDNA c) positive anti-Sm
5. 5. 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.
6. 6. 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.
7. 7. 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.
8. 8. 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 14

1. 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.
2. 2. 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.
3. 3. 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.
4. 4. Active severe neuropsychiatric or CNS SLE.
5. 5. 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.
6. 6. Presence of uncontrolled or New York Heart Association Class III or IV congestive heart failure.
7. 7. 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.
8. 8. Surgery (not considered minor by the investigator or the central adjudicator) within 4 weeks before Screening, or planned surgery during the study.
9. 9. 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.
10. 10. Malignancy within 5 years except successfully treated in situ cervical cancer, resected squamous cell or basal cell carcinoma of the skin.
11. 11. History of drug or alcohol abuse in the previous 12 months before screening in the opinion of the investigator.
12. 12. 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.
13. 13. 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.
14. 14. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients who achieve a response at Week 24, defined according to the BILAGBased Composite Lupus Assessment (BICLA) Response

Secondary endpoints 7

1. Proportion of patients who achieve response according to the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) at Week 24
2. Proportion of patients who achieve Lupus Low Disease Activity State (LLDAS) at Week 24.
3. Time to flare
4. Proportion of patients achieving prednisone equivalent dose ≤ 5 mg/day by the Week 12 visit and maintained through Week 24 with no disease worsening
5. Proportion of patients who achieve a ≥ 50% improvement from baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity (CLASI-A) score (CLASI-50 response) at Week 24 compared with baseline
6. Proportion of patients who achieve ≥ 50% decrease in active joint count (Joint-50 response) at Week 24 compared with baseline
7. Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at Week 24

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Zenas Biopharma (USA) LLC

Sponsor organisation

Zenas Biopharma (USA) LLC

Address

852 Winter Street Suite 250

City

Waltham

Postcode

02451-1439

Country

United States

Scientific contact point

Organisation

Zenas Biopharma (USA) LLC

Contact name

Allen Poma

Public contact point

Organisation

Zenas Biopharma (USA) LLC

Contact name

Allen Poma

Third parties 12

Locations

10 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 159 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications