Engineered B Cell Therapy for Mucopolysaccharidosis I

Recruiting at 1 trial location

Overseen By Jake Wesley, PharmD, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Immusoft Corporation

Must not be taking: Immune suppressants, Oxygen therapy

Disqualifiers: Cancer, Autoimmune disorders, HSCT, others

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

Compensation: Varies

Number of Visits: 25

Duration: 1 day

2 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ISP-001 for adults with Mucopolysaccharidosis Type I, specifically Hurler-Scheie and Scheie syndromes. The trial aims to determine the treatment's safety and its effects on the condition. Participants will receive a dose of engineered B cells, a type of immune cell, to potentially improve disease symptoms. Ideal candidates are those diagnosed with one of these syndromes who can travel to the study site for follow-up visits. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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, if you require systemic immune suppression or continuous supplemental oxygen, you may not be eligible to participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ISP-001 appears safe in early tests. One study observed the drug's effects and improvements in function up to nine months after a single dose, suggesting the treatment might be well-tolerated.

As ISP-001 undergoes its first human tests, the trial is in Phase 1. This phase primarily focuses on safety, assessing how the body reacts to the treatment and ensuring any side effects remain manageable for participants.

Overall, while the data remains preliminary, positive signs indicate that ISP-001 could be safe for human use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for Mucopolysaccharidosis I, which often includes enzyme replacement therapy and hematopoietic stem cell transplantation, ISP-001 uses autologous plasmablasts, a type of engineered B cell, to address the condition. This treatment is unique because it involves modifying the patient's own B cells to produce the missing enzyme, potentially leading to a more targeted and lasting therapeutic effect. Researchers are excited about this approach as it offers the potential for a one-time treatment that could reduce the need for ongoing therapies and improve patient outcomes significantly.

What evidence suggests that ISP-001 might be an effective treatment for Mucopolysaccharidosis I?

Research has shown that ISP-001, a specially designed B cell therapy, holds promise for treating Mucopolysaccharidosis Type I. In early studies, patients experienced positive effects and improvements for up to nine months after just one dose. This trial will evaluate the effectiveness of ISP-001, administered as autologous plasmablasts (B cells) at a dose level of 5 x 10e7 cells/kg on Day 0. The treatment uses altered immune cells to produce a missing enzyme that helps break down certain sugars. Without this breakdown, these sugars can cause tissue damage and health problems. Initial findings suggest that this treatment could help manage symptoms and improve the quality of life for people with this condition. ^{1 2 3 4 5}

Who Is on the Research Team?

Immusoft Clinical Development

Principal Investigator

Immusoft of CA, Inc.

Are You a Good Fit for This Trial?

Adults over 18 with Mucopolysaccharidosis type I Hurler-Scheie or Scheie can join this trial. They must live close to the study site, have good kidney function and heart health, and be able to attend all follow-ups. Those with certain medical conditions, oxygen needs, immune suppression, past stem cell transplants or B cell cancers cannot participate.

Inclusion Criteria

I can stay within a 45-minute drive from the study site for at least 5 days after treatment.

I can travel to the study site for follow-up visits.

I have been diagnosed with a form of Mucopolysaccharidosis (MPS I).

Exclusion Criteria

I have a history of B cell cancer, EBV disease, or autoimmune disorders.

Any medical condition likely to interfere with assessment of safety or efficacy of the study treatment.

I need medication to suppress my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a dose of 5 x 10e7 cells/kg of autologous plasmablasts engineered to express α-L-iduronidase (IDUA) on Day 0

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and various biomarkers

24 weeks

Multiple visits (in-person and virtual) over 24 weeks

Long-term follow-up

Participants are monitored for long-term safety and biomarker levels, including glycosaminoglycan (GAG) and antibody levels

1 year

What Are the Treatments Tested in This Trial?

Interventions

• ISP-001

Trial Overview The trial is testing a new treatment using patients' own modified B cells (ISP-001) for adults with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie. It's a first-of-its-kind study focusing on safety and how well it works in humans.

How Is the Trial Designed?

Group I: Autologous Plasmablasts (B cells) Experimental Treatment 1 Intervention

Dose Level: 5 x 10e7 cells/kg on Day 0

Who Is Running the Clinical Trial?

Immusoft Corporation

Lead Sponsor

Trials

1

Recruited

2+

Immusoft of CA, Inc.

Lead Sponsor

Trials

1

Recruited

2+

Published Research Related to This Trial

Encapsulated genetically engineered human amniotic epithelial (IHAE) cells can effectively secrete the enzyme GUSB, which is crucial for treating Mucopolysaccharidosis type VII (MPSVII), a lysosomal storage disease, demonstrating therapeutic potential in both in vitro and in vivo experiments.

This method of encapsulation not only prevents harmful immune responses and tumor formation but also allows for controlled expression of GUSB, addressing the challenge of delivering therapies across the blood-brain barrier, which is critical for treating neurological symptoms associated with MPSVII.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encapsulation cell therapy for mucopolysaccharidosis type VII using genetically engineered immortalized human amniotic epithelial cells. Nakama, H., Ohsugi, K., Otsuki, T., et al.[2019]

Reprogramming erythroid cells to produce the lysosomal enzyme alpha-L-iduronidase (IDUA) showed promising results, with stable and elevated IDUA levels maintained for at least 9 months in MPS I chimeras after HSC transplantation.

This method not only corrected metabolic issues in MPS I mice, such as normalizing urinary glycosaminoglycan levels, but also significantly improved neurological function and tissue pathology, indicating a potential safe and effective strategy for systemic delivery of therapeutic proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reprogramming erythroid cells for lysosomal enzyme production leads to visceral and CNS cross-correction in mice with Hurler syndrome. Wang, D., Zhang, W., Kalfa, TA., et al.[2021]

Alpha-L-iduronidase enzyme replacement therapy has been developed as an effective treatment for patients with mucopolysaccharidosis I, particularly those with attenuated forms of the disease, as shown in recent Phase I/II and Phase III clinical trials.

While the therapy has proven effective for patients with less severe symptoms, further advancements are needed to address the more severe neurological and skeletal issues seen in Hurler syndrome patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alpha-L-iduronidase and enzyme replacement therapy for mucopolysaccharidosis I. Brooks, DA.[2022]

Laronidase enzyme replacement therapy led to significant and sustained reductions in urinary glycosaminoglycan levels in patients with attenuated mucopolysaccharidosis type I over a mean follow-up of 6.1 years, indicating effective treatment.

The therapy stabilized disease progression in most patients, with younger patients (under 10 years at treatment initiation) showing better maintenance of health measures and fewer complications compared to older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Long-Term Treatment with Laronidase in Patients with Mucopolysaccharidosis Type I. Laraway, S., Mercer, J., Jameson, E., et al.[2022]

Valanafusp alpha, an IgG-IDUA fusion protein designed to cross the blood-brain barrier, shows a four-fold increase in plasma clearance in children with MPSI compared to adults, indicating a need for adjusted dosing in pediatric patients.

The pharmacokinetic profile of valanafusp alpha is similar to that of the standard enzyme replacement therapy, laronidase, suggesting that it may be an effective alternative for treating CNS involvement in MPSI without significant effects on plasma glucose levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma Pharmacokinetics of Valanafusp Alpha, a Human Insulin Receptor Antibody-Iduronidase Fusion Protein, in Patients with Mucopolysaccharidosis Type I. Pardridge, WM., Boado, RJ., Giugliani, R., et al.[2019]

Hematopoietic cell transplantation (HCT) has been successfully used to treat over 500 patients with mucopolysaccharidosis type IH (MPS IH; Hurler syndrome) for nearly 30 years, demonstrating its efficacy as a long-term treatment option.

The introduction of enzyme replacement therapy (ERT) with recombinant alpha-L-iduronidase (IDUA) has expanded treatment options for less severe forms of MPS I, and combining ERT with HCT has been explored in over 50 MPS IH patients, indicating a potential shift towards multimodal therapies in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

alpha-L-iduronidase therapy for mucopolysaccharidosis type I. Tolar, J., Orchard, PJ.[2021]

Galsulfase enzyme replacement therapy (ERT) initiated in adulthood for patients with mucopolysaccharidosis (MPS) VI was well tolerated and led to a significant reduction in urinary glycosaminoglycans (uGAG) levels by an average of 66% over a median follow-up of 7.2 years.

While the 6-minute walk test showed a slight decrease in distance, improvements were noted in stair climbing performance, suggesting that ERT may help stabilize certain physical functions in MPS VI patients over the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzyme replacement therapy initiated in adulthood: Findings from the mucopolysaccharidosis VI Clinical Surveillance Program. Lampe, C., Harmatz, PR., Parini, R., et al.[2020]

In a study of 39 patients with mucopolysaccharidosis type I (MPS I), bone marrow transplantation (BMT) significantly reduced the incidence of airway complications during anesthesia to 14%, with no failed intubations, compared to a higher rate of 57% in patients receiving enzyme replacement therapy (ERT).

Overall, the study found that the incidence of airway complications in MPS I patients was lower than previously reported at 31%, indicating that advancements in treatment and airway management techniques are improving safety in anesthesia for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mucopolysaccharidosis type I (Hurler syndrome) and anesthesia: the impact of bone marrow transplantation, enzyme replacement therapy, and fiberoptic intubation on airway management. Kirkpatrick, K., Ellwood, J., Walker, RW.[2012]

Encapsulating recombinant cells that produce the enzyme IDUA within alginate microcapsules shows promise for treating Mucopolysaccharidosis type I (MPS I), as it initially increases IDUA activity and reduces harmful glycosaminoglycan (GAG) storage in affected mice.

However, the long-term effectiveness is limited due to inflammation and fibrosis around the capsules, which leads to a decrease in IDUA activity and the development of antibodies against the enzyme, indicating a need for improvements in the encapsulation method to enhance stability and reduce immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal implant of recombinant encapsulated cells overexpressing alpha-L-iduronidase partially corrects visceral pathology in mucopolysaccharidosis type I mice. Baldo, G., Mayer, FQ., Martinelli, B., et al.[2018]

Citations

1. biopharmatrend.com biopharmatrend.com/news/immusoft-announces-positive-data-for-first-engineered-b-cell-therapy-in-clinical-trial-961/

Immusoft Announces Positive Data for First Engineered B ... MPS I severely limits the body's ability to break down certain sugars, leading to tissue damage and reduced life expectancy. How ISP-001 Works: ...

2. immusoft.com immusoft.com/2024/09/23/immusoft-to-announce-positive-phase-1-data-for-first-engineered-b-cell-therapy-in-a-clinical-trial/

Immusoft to Announce Positive Phase 1 Data for First ... Pharmacodynamic effects and functional improvements were observed through nine months post-dosing with a single administration of ISP-001.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05682144?term=AREA%5BConditionSearch%5D(Mucopolysaccharidosis%20Ih%20(Hurler%20Syndrome))&rank=2

ISP-001: Sleeping Beauty Transposon-Engineered B Cells ... This is a Phase 1, first-in-human, open-label, single-arm study in which adult patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie are treated ...

4. withpower.com withpower.com/trial/phase-1-mucopolysaccharidoses-2023-ceb2d

Engineered B Cell Therapy for Mucopolysaccharidosis I This trial tests ISP-001, which uses modified immune cells to help adults with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie by making a missing ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05682144

ISP-001: Sleeping Beauty Transposon-Engineered B Cells for ... A first-in-human study using ISP-001 in adult patients with Mucopolysaccharidosis Type I Hurler-Scheie and Scheie.