IDP-023 + Ocrelizumab for Multiple Sclerosis

Recruiting at 5 trial locations

Overseen By Indapta Therapeutics, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Indapta Therapeutics, INC.

Must be taking: Ocrelizumab

Disqualifiers: Relapsing MS, CNS tumor, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

34 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since participants must have been dosed with ocrelizumab within the prior 6 months, it seems that continuing this medication is required.

What data supports the effectiveness of the drug IDP-023 + Ocrelizumab for treating multiple sclerosis?

Ocrelizumab has been shown to reduce disease progression in multiple sclerosis, particularly in patients with increased disability, and has been effective in those with a suboptimal response to previous treatments. ^{1 2 3 4 5}

What is known about the safety of ocrelizumab for multiple sclerosis?

Ocrelizumab has been studied for its safety in treating multiple sclerosis, with some reports of adverse events like delayed-onset neutropenia (a drop in white blood cells). Overall, its safety profile is still being evaluated through ongoing studies and real-world data. ^{1 3 6 7 8}

How does the drug IDP-023 + Ocrelizumab differ from other multiple sclerosis treatments?

The combination of IDP-023 with Ocrelizumab for multiple sclerosis is unique because Ocrelizumab is the first drug approved for both relapsing-remitting and primary progressive forms of the disease, targeting B cells to reduce disease progression. The specific role of IDP-023 in this combination is not detailed, suggesting it may offer a novel approach or enhancement to existing therapies. ^{1 2 9 10 11}

Research Team

Indapta Therapeutics, Inc.

Principal Investigator

Indapta Therapeutics, INC.

Eligibility Criteria

This trial is for patients with progressive multiple sclerosis who have not responded to standard treatments. Participants must be adults capable of giving consent and should not have other autoimmune diseases, oral cancers, or conditions that could interfere with the study.

Inclusion Criteria

My MS is diagnosed as primary or secondary progressive.

I have mobility issues in my legs.

My disability level is moderate to severe but I can still walk.

Exclusion Criteria

I cannot undergo an MRI scan.

Contraindication for gadolinium

My MS is currently in a relapsing-remitting phase or is actively worsening.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

The primary objectives 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 for Part 2.

up to 21 days

Multiple visits for dose administration and monitoring

Dose Expansion

The objective is to assess the biologic activity of IDP-023 in combination with IL-2 and ocrelizumab on autoreactive immune cells in PPMS.

2 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• IDP-023

Trial Overview The trial tests a combination treatment using IDP-023 g-NK cells with Ocrelizumab and other drugs like Mesna, Cyclophosphamide, Interleukin-2, and Fludarabine. It's an early-phase study to check safety and effects on immune cells in MS patients.

Participant Groups

Group I: Part 2 (dose expansion): IDP-023 in combination with IL-2 and ocrelizumab Experimental Treatment 6 Interventions

MS patients treated with the recommended dose of IDP-023 in combination with IL-2 and ocrelizumab

Group II: Part 1 (dose escalation): IDP-023 in combination with IL-2 and ocrelizumab Experimental Treatment 6 Interventions

MS patients treated with multiple doses of IDP-023 in combination with IL-2 and ocrelizumab

IDP-023 is already approved in United States for the following indications:

Approved in United States as IDP-023 for:

• None - Currently under investigation for Non-Hodgkin lymphoma and multiple myeloma

Who Is Running the Clinical Trial?

Indapta Therapeutics, INC.

Lead Sponsor

Trials

2

Recruited

160+

Findings from Research

Ocrelizumab, an anti-CD20 monoclonal antibody, is effective in reducing disability progression in primary progressive multiple sclerosis, but it can lead to severe late-onset neutropenia as a rare side effect.

In a reported case, a 34-year-old male developed severe neutropenia 42 days after receiving ocrelizumab, requiring hospitalization and treatment, highlighting the need for patient awareness and monitoring for symptoms like fever.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe Delayed-Onset Neutropenia Induced by Ocrelizumab. Baird-Gunning, J., Yun, J., Stevenson, W., et al.[2022]

In a post hoc analysis of pivotal trials, ocrelizumab significantly reduced the risk of confirmed disability progression in multiple sclerosis patients with higher baseline disability (Expanded Disability Status Scale scores ≥4.0).

The analysis included patients from the OPERA trials (relapsing MS) and ORATORIO trial (primary progressive MS), showing that ocrelizumab was more effective than interferon β-1a and placebo in slowing disability progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. Wolinsky, JS., Engmann, NJ., Pei, J., et al.[2022]

Ocrelizumab is an effective B-cell-targeted therapy for multiple sclerosis (MS), showing significant reductions in relapse rates and disability progression in both relapsing and primary progressive MS, based on data from multiple phase III trials involving human subjects.

Approved in March 2017, ocrelizumab is the first treatment specifically for primary progressive MS, with a recommended dosing of 600 mg intravenously every 6 months, though it may cause infusion-related reactions and infections as side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis. Stahnke, AM., Holt, KM.[2022]

In a phase 3 trial involving 680 patients with relapsing-remitting multiple sclerosis who had previously shown suboptimal responses to other treatments, ocrelizumab achieved a high rate of 'no evidence of disease activity' (NEDA) at 74.8% after 96 weeks, indicating its efficacy in managing the disease.

The highest NEDA rates were observed in patients enrolled based on MRI activity alone (80.6%) and those with lower disability scores (EDSS <2.5), suggesting that ocrelizumab is particularly effective in these subgroups, with no new safety concerns reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis with suboptimal response to prior disease-modifying therapies: A primary analysis from the phase 3b CASTING single-arm, open-label trial. Vermersch, P., Oreja-Guevara, C., Siva, A., et al.[2022]

Patients with relapsing multiple sclerosis treated with ocrelizumab (OCR) showed significantly reduced immune responses to certain vaccines compared to those receiving standard treatment, indicating that OCR may impair the effectiveness of nonlive vaccines.

Despite the attenuated responses, patients on OCR can still mount a potentially protective humoral response to seasonal influenza vaccines, suggesting that vaccination remains important for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. Bar-Or, A., Calkwood, JC., Chognot, C., et al.[2021]

In a study of 1104 multiple sclerosis patients treated with ocrelizumab over a median follow-up of 1.3 years, 94.5% were free of MRI activity, indicating strong effectiveness in stabilizing the disease.

Ocrelizumab was generally well tolerated, with only 10% of patients reporting side effects, primarily infusion-related reactions and infections, aligning with safety profiles observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study. Pontieri, L., Blinkenberg, M., Bramow, S., et al.[2022]

In a review of 78 studies involving 4498 patients, 61.3% of those treated with ocrelizumab experienced adverse events, with the most common being infections (39.2%) and infusion-related reactions (26.2%).

Ocrelizumab was associated with a higher risk of infections compared to beta-interferon, particularly herpes-related and respiratory infections, while the risk of serious adverse events was similar between ocrelizumab and comparator groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. Ng, HS., Rosenbult, CL., Tremlett, H.[2022]

In a study of 228 multiple sclerosis patients treated with ocrelizumab, 91.2% of those with relapsing forms of MS achieved no evidence of disease activity (NEDA) after one year, indicating strong effectiveness in managing the disease.

The treatment was generally well-tolerated, with the most common side effects being infusion-related reactions and infections, particularly urinary tract infections, suggesting a favorable safety profile in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. Fernandez-Diaz, E., Perez-Vicente, JA., Villaverde-Gonzalez, R., et al.[2021]

Ocrelizumab is the first approved treatment for both relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS), demonstrating significant efficacy in slowing disability progression in PPMS patients at 12 and 24 weeks.

The safety profile of ocrelizumab aligns with findings from clinical trials, showing no unexpected safety concerns, which supports its use in managing multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab: its efficacy and safety in multiple sclerosis. Juanatey, A., Blanco-Garcia, L., Tellez, N.[2019]

Ocrelizumab significantly reduces relapse rates and disability progression in adults with relapsing-remitting multiple sclerosis (RRMS) compared to interferon beta-1a, with moderate-certainty evidence from studies involving 2551 participants.

For primary progressive multiple sclerosis (PPMS), ocrelizumab may lead to a higher rate of adverse events compared to placebo, but it also shows potential in reducing disability progression, based on low-certainty evidence from trials lasting at least 120 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. Lin, M., Zhang, J., Zhang, Y., et al.[2023]

In a study of 130 individuals with relapsing and progressive multiple sclerosis, treatment with ocrelizumab led to significant improvements in health-related quality of life (HRQOL) after 12 months, particularly in mental health domains.

The improvements were measured using patient-reported outcome tools, showing enhanced scores in areas like vitality, emotional health, and reduced anxiety, indicating that ocrelizumab not only affects physical symptoms but also positively impacts mental well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of ocrelizumab on health-related quality of life in individuals with multiple sclerosis. Glanz, BI., Zurawski, J., Casady, EC., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Severe Delayed-Onset Neutropenia Induced by Ocrelizumab. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

An exploratory analysis of the efficacy of ocrelizumab in patients with multiple sclerosis with increased disability. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Ocrelizumab: A New B-cell Therapy for Relapsing Remitting and Primary Progressive Multiple Sclerosis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ocrelizumab in patients with relapsing-remitting multiple sclerosis with suboptimal response to prior disease-modifying therapies: A primary analysis from the phase 3b CASTING single-arm, open-label trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of ocrelizumab on vaccine responses in patients with multiple sclerosis: The VELOCE study. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety profile of ocrelizumab for the treatment of multiple sclerosis: a systematic review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Real-world experience of ocrelizumab in multiple sclerosis in a Spanish population. [2021]

9. Spain pubmed.ncbi.nlm.nih.gov

Ocrelizumab: its efficacy and safety in multiple sclerosis. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Ocrelizumab for multiple sclerosis. [2023]

11. United States pubmed.ncbi.nlm.nih.gov

The impact of ocrelizumab on health-related quality of life in individuals with multiple sclerosis. [2022]