Progressive Multiple Sclerosis
Conditions
Keywords
Multiple sclerosis, Refractory multiple sclerosis, Progressive multiple sclerosis, Obecabtagene autoleucel, Obe-cel
Brief summary
The main purpose of this study is to evaluate if obe-cel is safe or causes any side effects in adults with refractory progressive MS. The study also plans to assess if obe-cel can show early signs of efficacy in MS. The trial includes only 1 group of participants (single-arm). The study population comprises participants with progressive forms of MS, not responsive to highly effective therapies. Upon confirmation of study eligibility, participants will receive chemotherapy (used here for lymphodepletion) over 1 to 3 days in preparation for receiving a single obe-cel infusion. Participants will be checked closely in the 28 days following obe-cel treatment. After this, participants will be monitored to evaluate safety and efficacy up to 24 months.
Detailed description
This is a Phase 1 study to determine the safety, tolerability, and preliminary efficacy of obe-cel in participants with refractory progressive forms of multiple sclerosis. The study comprises 3 periods: Screening Period: From Day -30 to enrolment Treatment Period: From day of enrolment to End of Treatment (EOT) or Day 1 - Participants will be evaluated to confirm eligibility for lymphodepletion, and thereafter receive lymphodepletion to enhance treatment efficacy and cluster of differentiation (CD)19 chimeric antigen receptor (CAR) T cell survival. 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. Post treatment Period: From Day 1 to End of Study all participants will be followed up for efficacy and safety evaluation.
Interventions
BIOLOGICALObecabtagene autoleucel (obe-cel)
Obecabtagene autoleucel (obe-cel) given as a single infusion.
Sponsors
Autolus Limited
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
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Willing and able to give written informed consent for participation in the study. * Ability and willingness to adhere to the protocol's Schedule of Activities and other requirements. * Participants must be 18 to 60 years of age inclusive at the time of signing the informed consent form. * A female participant is eligible to participate if she is not pregnant or breastfeeding. * Current diagnosis of PMS. * Must have been treated previously with 2 disease-modifying therapies.
Exclusion criteria
* Any medications prohibited by the protocol. * Highly active multiple sclerosis. * Diagnosis of another autoimmune central nervous system condition. * Active or uncontrolled fungal, bacterial, viral infection. * History of malignant neoplasms unless disease-free for at least 24 months. * History of heart, lung, kidney, liver transplant or hematopoietic stem cell transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants receiving obe-cel who experience dose-limiting toxicities (DLTs)) | Up to Day 28 | — |
| To evaluate the safety of obe-cel in participants with refractory forms of progressive multiple sclerosis (PMS) | Up to end of study | To evaluate the safety of obe-cel in participants with refractory forms of progressive multiple sclerosis (PMS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the preliminary efficacy of obe-cel in participants with refractory forms of PMS using Expanded Disability Status Scale (EDSS) - Change from baseline in EDSS | Up to Month 24 | The EDSS is based on a standardized neurological examination focussing on assessment of 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel / bladder and cerebral). The range of the EDSS includes 20 half steps from 0 to 10, with EDSS step 0 corresponding to a completely normal examination and EDSS step 10 to death due to MS. |
| To evaluate the preliminary efficacy of obe-cel in participants with refractory forms of PMS using Timed 25-foot Walk Test (T25FWT). | Up to Month 24 | Change from baseline in T25FWT |
| To evaluate the preliminary efficacy of obe-cel in participants with refractory forms of PMS using 9-hole Peg Test (9-HPT) | Up to Month 24 | Change from baseline in 9-HPT |
| To evaluate the preliminary efficacy of obe-cel in participants with refractory forms of PMS using Symbol Digit Modalities Test (SDMT) | Up to Month 24 | Change from baseline in SDMT |
Countries
Spain, United Kingdom, United States
Contacts
CONTACTAutolus Ltd
Outcome results
None listed