IDP-023 g-NK Cells Plus Ocrelizumab in Patients With Progressive Multiple Sclerosis

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.

• IDP-023 (Drug): NK cell therapy
• Ocrelizumab (Drug), also known as Ocrevus: Anti-CD20 antibody therapy
• Interleukin-2 (Drug), also known as Proleukin: Immune cytokine
• Cyclophosphamide (Drug): Lymphodepleting chemotherapy
• Fludarabine (Drug): Lymphodepleting chemotherapy
• Mesna (Drug): Chemoprotectant

Primary outcomes

• 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 outcomes

• 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

Sex: All, ages: 18 Years to 65 Years

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.

• Indapta Therapeutics, Inc., Study director, Indapta Therapeutics, INC.