Clinical trial NCT06677710: IDP-023 g-NK Cells Plus Ocrelizumab in Patients With Progressive Multiple Sclerosis
Official title: A Phase 1B Study of IDP-023 g-NK Cells Plus Ocrelizumab in Patients With Refractory Primary and Secondary Progressive Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE1
Conditions: Multiple Sclerosis
Primary Progressive Multiple Sclerosis (PPMS)
Secondary Progressive Multiple Sclerosis (SPMS)
Non-Active Secondary Progressive Multiple Sclerosis
Non-Active SPMS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Autoimmune Diseases
Demyelinating Diseases
Immune System Diseases
Demyelinating Autoimmune Diseases, Central Nervous System (CNS)
Keywords: Progressive Multiple Sclerosis
Refractory Progressive Multiple Sclerosis
IDP-023
autoimmune disease
Cellular Therapy
MS
Natural Killer Cells
Lead sponsor: Indapta Therapeutics, INC.
Sponsor class: INDUSTRY
First posted: 2024-11-07
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Multiple ascending dose and dose-expansion study of IDP-023 in combination with interleukin-2 (IL-2) and ocrelizumab.
Primary purpose: TREATMENT

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.

Eligibility criteria: Key Inclusion Criteria:

* Confirmed diagnosis of primary or non-active secondary progressive MS (SPMS) based on the 2017 revisions of the McDonald criteria.
* Dosed with ocrelizumab within the prior 6 months.
* Expanded Disability Status Scale (EDSS) at screening from 3.0 to 6.5 points.
* Score of ≥2.0 on the Functional Systems (FS) scale for the pyramidal system that is due to lower extremity findings.
* 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 Exclusion Criteria:

* Relapsing remitting MS at screening or active SPMS at screening.
* Inability to complete an MRI.
* Contraindication for gadolinium.
* 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).
* Impaired cardiac function or history of clinical significant cardiac disease.
* Human immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection.

Primary outcomes:
measure: Incidence of AEs and SAEs - (Part 1)
timeFrame: 1 year
measure: Incidence of dose-limiting toxicities (DLTs) of IDP-023 in combination with IL-2 and Ocrelizumab (Part 1)
timeFrame: up to 21 days
measure: Change in cellular response of autoreactive immune cells to antigen (Part 2)
timeFrame: 2 years
Secondary outcomes:
measure: Change in cellular response of autoreactive immune cells to antigen (Part 1)
timeFrame: 2 year
measure: Incidence of AEs and SAEs - (Part 2)
timeFrame: 2 years
measure: PK (PK; maximum drug concentration) of IDP-023 - (Part 1/2)
timeFrame: 2 years
measure: PK (area under the concentration-time curve) of IDP-023 - (Part 1/2)
timeFrame: 2 years
measure: PK (concentration reached by the drug immediately before the next dose is administered) of IDP-023 - (Part 1/2)
timeFrame: 2 years
measure: Time to onset of sustained disability progression over the treatment period, deﬁned as an increase in Expanded Disability Status Scale (EDSS) - (Part 1/2)
timeFrame: 2 years
measure: 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)
timeFrame: 2 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Orlando - Adventist Health System/Sunbelt, Inc.
state: Florida
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
Study officials:
affiliation: Indapta Therapeutics, INC.
name: Indapta Therapeutics, Inc.
role: STUDY_DIRECTOR
References: