Lupus Nephritis
Conditions
Keywords
Systemic lupus erythematosus, Refractory systemic lupus erythematosus, Lupus nephritis, Obecabtagene autoleucel, Obe-cel
Brief summary
The purpose of this trial is to evaluate the efficacy and safety of obecabtagene autoleucel (obe-cel) administered once following lymphodepletion in participants with severe, refractory systemic lupus erythematosus (SLE) and active lupus nephritis (LN).
Detailed description
This is a Phase 2 study to determine the efficacy and safety of obe-cel in participants with severe, refractory SLE with active LN. The study comprises 3 periods: 1. Screening Period: From Day -30 (+7) to Day of Enrollment 2. Treatment Period: From Day -8 to Day 1 - Participants will be evaluated to confirm eligibility for lymphodepletion, and thereafter receive lymphodepletion. Obe-cel Administration: If the participant's eligibility for receiving obe-cel infusion is confirmed, the participant is to receive a single obe-cel infusion on Day 1. 3. Post-treatment Period: From Day 1 to End of Study all participants will be followed up for efficacy and safety evaluation.
Interventions
BIOLOGICALObecabtagene autoleucel
Obecabtagene autoleucel (obe-cel) given as a single infusion
Sponsors
Autolus Limited
PPD Development, LP
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, single group assignment, open-label
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to give written informed consent for participation in the study or written informed consent signed by a legal guardian or representative * Ability and willingness to adhere to protocol's Schedule of Activities and other requirements * Participants must be 12 to 65 years of age inclusive at the time of signing the informed consent. * Female Participants: - a female participant is eligible to participate if she is not pregnant or breastfeeding * Diagnosis of SLE fulfilling the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification Criteria for Systemic Lupus Erythematosus. * Positive for at least 1 of the following autoantibodies: antinuclear antibodies (ANA), or anti-dsDNA or anti-Smith. * Severe, Active SLE defined as: * SLEDAI-2K score of ≥ 8 points AND * Severe active LN based on a renal biopsy: Class III, IV or V (V only in combination with class III or IV) * Refractory SLE defined as failure to previous lines of therapy
Exclusion criteria
* Prior treatment at any time with anti-CD19 therapy * More than 1 acute, severe lupus-related flare during screening that needs immediate treatment and/or makes the immunosuppressive washout impossible * Significant, likely irreversible organ damage related to SLE (e.g., end-stage renal disease) that in the opinion of the Investigator renders CD19 CAR T cell therapy unlikely to benefit the participant * History of primary antiphospholipid antibody syndrome * Active or uncontrolled fungal, bacterial, or viral infection * History of malignant neoplasms unless disease free for at least 24 months * History of heart, lung, renal, liver transplant or hematopoietic stem cell transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants who achieve complete renal response (CRR) | Month 6 | CRR is a composite endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving remission per Definition of Remission in SLE (DORIS) criteria | Month 6 | DORIS is a composite endpoint |
| Proportion of participants achieving CRR over time | Up to Month 24 | CRR is a composite endpoint |
| Time to CRR | Up to Month 24 | CRR is a composite endpoint |
| Proportion of participants with Partial Renal Response (PRR) | Up to Month 24 | PRR is a composite endpoint |
| Time to PRR | Up to Month 24 | PRR is a composite endpoint |
| Proportion of participants achieving remission per DORIS criteria over time | Up to Month 24 | DORIS is a composite endpoint |
| Time to achieving remission per DORIS criteria | Up to Month 24 | DORIS is a composite endpoint |
| Time to renal flare | Up to Month 24 | Renal flare is a composite endpoint |
| Proportion of participants achieving Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score of 0 over time | Up to Month 24 | SLEDAI-2K is a composite index of disease activity |
| Proportion of participants achieving Lupus Low Disease Activity State (LLDAS) over time | Up to Month 24 | LLDAS is a composite endpoint |
| Time to LLDAS | Up to Month 24 | LLDAS is a composite endpoint |
| Time to first disease flare according to Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI-2K Flare Index (SFI) post-obe-cel infusion | Up to Month 24 | SFI is a composite index to identify disease flares |
| To evaluate safety of obe-cel | Up to Month 24 | Proportion of participants with adverse events (AEs) |
Countries
Brazil, Greece, United Kingdom, United States, Vietnam
Contacts
CONTACTAutolus Ltd
Outcome results
None listed