IDP-023 g-NK Cells Plus Ocrelizumab in Patients With Progressive Multiple Sclerosis
- Conditions
- Multiple SclerosisPrimary Progressive Multiple Sclerosis (PPMS)Secondary Progressive Multiple Sclerosis (SPMS)Non-Active Secondary Progressive Multiple SclerosisNon-Active SPMSAutoimmune Diseases of the Nervous SystemNervous System DiseasesAutoimmune DiseasesDemyelinating DiseasesImmune System Diseases
- Interventions
- Registration Number
- NCT06677710
- Lead Sponsor
- Indapta Therapeutics, INC.
- Brief Summary
This is an open label, Phase 1b, multiple ascending dose, and dose-expansion study of IDP-023 administered in combination with interleukin-2 (IL-2) and ocrelizumab to evaluate the safety, tolerability, and biologic activity on autoreactive immune cells in patients with refractory progressive multiple sclerosis.
- Detailed Description
IDP-023 is an off-the-shelf product made from allogeneic g-natural killer (NK) cells, which are a natural subset of NK cells that develop over the course of an immune response in people who have been exposed to the human cytomegalovirus (HCMV). These cells may be particularly effective at targeting and killing the cells that cause the immune system to attack the nervous system in multiple sclerosis (MS). By killing these harmful cells, g-NK cells may help to slow down or potentially stop the progression of MS. When combined with other approved treatments like ocrelizumab, g-NK cells might offer even greater benefit for people with MS.
This is an open label, Phase 1b, multiple ascending dose, and dose-expansion study of IDP- 023 administered in combination with IL-2 and ocrelizumab to evaluate the safety, tolerability, and biologic activity on autoreactive immune cells in patients with primary progressive multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS).
The study is divided into Part 1, a dose escalation phase, and Part 2, an expansion phase.
Part 1 (Escalation Period): The primary objectives of Part 1 are to define the safety of different dose levels of IDP-023 in combination with IL-2 and ocrelizumab and to define the recommended cell dose that will be used for Part 2 (recommended Part 2 dose; RP2D).
Part 2 (Expansion Period): The objective of the Part 2 expansion phase is to assess the biologic activity of IDP-023 in combination with IL-2 and ocrelizumab on autoreactive immune cells in PPMS.
Recruitment & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 34
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Confirmed diagnosis of primary or non-active secondary progressive MS (SPMS) based on the 2017 revisions of the McDonald criteria.
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Dosed with ocrelizumab within the prior 6 months.
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Expanded Disability Status Scale (EDSS) at screening from 3.0 to 6.5 points.
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Score of ≥2.0 on the Functional Systems (FS) scale for the pyramidal system that is due to lower extremity findings.
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Disease duration from the onset of MS symptoms:
- Less than 15 years in patients with an EDSS at screening >5.0.
- Less than 10 years in patients with an EDSS at screening ≤5.0.
Key
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Relapsing remitting MS at screening or active SPMS at screening.
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Inability to complete an MRI.
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Contraindication for gadolinium.
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Known presence of other neurological disorders, including but not limited to the following:
- History or known presence of CNS or spinal cord tumor (e.g., meningioma, glioma).
- History or known presence of infectious causes of myelopathy (e.g., syphilis, Lyme disease, Human T-lymphotropic virus 1 [HTLV-1], herpes zoster myelopathy).
- History or known presence of systemic autoimmune disorders potentially causing progressive neurologic disease (e.g., lupus, antiphospholipid antibody syndrome, Sjögren's syndrome, Behçet's disease).
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Impaired cardiac function or history of clinical significant cardiac disease.
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Human immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab Cyclophosphamide MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab Ocrelizumab MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab Interleukin-2 MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab Mesna MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab IDP-023 MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab Interleukin-2 MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab Cyclophosphamide MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab Fludarabine MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab Fludarabine MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab Mesna MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab IDP-023 MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab Ocrelizumab MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab
- Primary Outcome Measures
Name Time Method Incidence of AEs and SAEs - (Part 1) 1 year Escalation Period
Incidence of dose-limiting toxicities (DLTs) of IDP-023 in combination with IL-2 and Ocrelizumab (Part 1) up to 21 days Escalation Period
Change in cellular response of autoreactive immune cells to antigen (Part 2) 2 years Expansion Period
- Secondary Outcome Measures
Name Time Method Change in cellular response of autoreactive immune cells to antigen (Part 1) 2 year Escalation Period
Incidence of AEs and SAEs - (Part 2) 2 years Expansion Period
PK (PK; maximum drug concentration) of IDP-023 - (Part 1/2) 2 years Escalation and Expansion periods
PK (area under the concentration-time curve) of IDP-023 - (Part 1/2) 2 years Escalation and Expansion periods
PK (concentration reached by the drug immediately before the next dose is administered) of IDP-023 - (Part 1/2) 2 years Escalation and Expansion periods
Time to onset of sustained disability progression over the treatment period, defined as an increase in Expanded Disability Status Scale (EDSS) - (Part 1/2) 2 years Escalation and Expansion periods
Biologic activity of IDP-023 in the CSF over the treatment period - (Part 1/2) over the treatment period, defined as an increase in EDSS - (Part 1/2) 2 years Escalation and Expansion periods
Trial Locations
- Locations (5)
Stanford University
🇺🇸Stanford, California, United States
University of Colorado Hospital
🇺🇸Aurora, Colorado, United States
AdventHealth Orlando - Adventist Health System/Sunbelt, Inc.
🇺🇸Orlando, Florida, United States
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States