Intrathecal SHP611 for Metachromatic Leukodystrophy

(EMBOLDEN Trial)

Not currently recruiting at 32 trial locations

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Shire

Disqualifiers: Multiple sulfatase disorder, BMT, HSCT, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 106 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether SHP611, an experimental treatment, helps children with Metachromatic Leukodystrophy (MLD) maintain mobility for a longer period. The treatment involves injecting the medicine into the spinal fluid, which surrounds the brain and spinal cord, to assess its effects on movement and speech. The study will also evaluate how well children tolerate the treatment. Ideal participants are children with MLD who have movement issues and have received a diagnosis from a doctor. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that SHP611 is likely to be safe for humans?

Research has shown that SHP611, a treatment for Metachromatic Leukodystrophy (MLD), has been tested for safety and tolerability. In earlier studies, researchers administered SHP611 directly into the fluid around the spine. Participants generally tolerated this method well. Most side effects were mild to moderate, with no severe reactions directly attributed to the treatment. This suggests that SHP611 is generally safe for children with MLD. However, individual experiences can vary, and ongoing studies aim to confirm these results. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Metachromatic Leukodystrophy, which primarily focus on managing symptoms, SHP611 offers a novel approach by delivering the medication intrathecally, directly into the spinal fluid. This method allows for potentially more effective targeting of the central nervous system, where this disease primarily manifests. Researchers are excited about SHP611 because it could lead to better outcomes by directly addressing the neurological aspects of the condition, potentially slowing disease progression more effectively than current therapies.

What evidence suggests that SHP611 might be an effective treatment for Metachromatic Leukodystrophy?

Research has shown promising results for SHP611 in treating Metachromatic Leukodystrophy (MLD). In earlier studies, administering SHP611 directly into the spinal fluid helped children maintain their mobility for a longer period. Although detailed information about SHP611's effectiveness in humans remains limited, its delivery method targets the brain and spinal cord directly, which is crucial for MLD. The treatment aims to improve movement and speech abilities. Early signs suggest patients tolerate it well, offering hope for those affected by this condition. ^{1 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

Shire

Are You a Good Fit for This Trial?

This trial is for children with Metachromatic Leukodystrophy (MLD) who have movement issues due to the disease. They must be diagnosed with MLD, able to follow the study plan, and meet specific age and GMFC-MLD criteria. Children can't join if they've had certain treatments like bone marrow transplants or gene therapy, are enrolled in another drug study, or have conditions that make it unsafe to participate.

Inclusion Criteria

I have difficulty walking due to MLD.

The participant's level of functioning must meet specific criteria for each group during the screening.

Your white blood cells do not have enough ASA activity compared to the normal range in the lab.

Exclusion Criteria

I have had a bone marrow, stem cell transplant, or gene therapy.

You are too small for the SOPH-A-PORT Mini S Access Port to be used.

Any other medical condition or serious comorbid illness that in the opinion of the investigator would preclude participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 150 mg of SHP611 intrathecally once weekly for 106 weeks

106 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Extension

Participants may opt into an extended treatment period beyond the initial 2 years

What Are the Treatments Tested in This Trial?

Interventions

• SHP611

Trial Overview The trial tests SHP611 given intrathecally (injected into spinal fluid) over approximately two years. It aims to see if this treatment helps children maintain their ability to move independently and assess its impact on movement and speech functions.

How Is the Trial Designed?

Group I: SHP611 Experimental Treatment 1 Intervention

Participants will receive 150 milligrams (mg) of SHP611 intrathecally (IT) via intrathecal drug delivery device (IDDD) or lumbar puncture (LP) once weekly for 106 weeks in six groups (Group A, B, C, D, E, and F) based on participant's age and motor dysfunction.

Who Is Running the Clinical Trial?

Shire

Lead Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

Takeda Development Center Americas, Inc.

Industry Sponsor

Trials

58

Recruited

10,800+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03771898

NCT03771898 | A Study of Intrathecal SHP611 in Children ... The main aim of the study is to determine if SHP611 given by injection into the spinal fluid that surrounds the brain and spinal cord (intrathecal; ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12205745/

Metachromatic Leukodystrophy: New Therapy Advancements ... Results were confirmed by a long-term study on efficacy and safety, which also showed that HSC-GT is influenced by MLD subtype, patient age, and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03771898?term=Metachromatic%20Leukodystrophy&viewType=Table&rank=10&tab=results

Study Results | A Study of Intrathecal SHP611 in Children ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12242458/

Lenmeldy (atidarsagene autotemcel) for individuals with early ... Among 7 participants with PSEJ MLD, 1 died from cerebral infarction. Three retained normal gait up to 12 years of age; 2 untreated matched ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0168365925009204

Encapsulated cells as an enzyme replacement therapy for ... Results of a phase I-II trial, performed in early symptomatic LI-MLD patients confirmed a good safety profile and, for patients that received ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S1096719220301529

Results from a phase 1/2 clinical trial We examined the safety and tolerability of intrathecally delivered recombinant human ASA (rhASA; SHP611, now TAK-611) in children with MLD.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/32792226/

Results from a phase 1/2 clinical trial We examined the safety and tolerability of intrathecally delivered recombinant human ASA (rhASA; SHP611, now TAK-611) in children with MLD (NCT01510028).

8. mayo.edu mayo.edu/research/clinical-trials/cls-20475710

A Study of Intrathecal SHP611 in Participants With Late ... The primary purpose of this study is to evaluate the effects of intrathecal (IT) administration of SHP611 on gross motor function, using the Gross Motor ...

9. mld.foundation mld.foundation/ert/

MLD Enzyme Replacement Therapy (ERT) Enzyme Replacement Therapy is an infusion (injection) of an enzyme designed to substitute for the missing ARSA enzyme that causes metachromatic leukodystrophy.