Intrathecal SHP611 for Metachromatic Leukodystrophy

(EMBOLDEN Trial)

Recruiting at 29 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

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if SHP611, injected into the fluid around the brain and spinal cord, can help children with Metachromatic Leukodystrophy (MLD) keep their ability to move and speak for a longer time. The study will also check how well children tolerate this treatment over a long period.

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.

What data supports the effectiveness of the drug SHP611 for treating metachromatic leukodystrophy?

The phase 1/2 clinical trial examined the safety and tolerability of SHP611 in children with metachromatic leukodystrophy, and secondary endpoints included changes in cerebrospinal fluid sulfatide levels and motor function, which are relevant to assessing the drug's effectiveness. ^{1 2 3 4 5}

Is intrathecal SHP611 (TAK-611) safe for humans?

A phase 1/2 clinical trial studied the safety of intrathecal SHP611 (now TAK-611) in children with metachromatic leukodystrophy and found it to be safe and well-tolerated. ^{4 5 6 7 8}

How does the drug SHP611 differ from other treatments for metachromatic leukodystrophy?

SHP611 is unique because it involves the intrathecal (directly into the spinal fluid) delivery of recombinant human arylsulfatase A, which is specifically designed to address the enzyme deficiency in metachromatic leukodystrophy, unlike other treatments that may not target this specific deficiency. ^{1 3 5 9 10}

Research Team

Study Director

Principal Investigator

Shire

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

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

Metachromatic leukodystrophy: A single-center longitudinal study of 45 patients. [2022]

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

Metachromatic leukodystrophy: a case of triplets with the late infantile variant and a systematic review of the literature. [2022]

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

Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Atidarsagene autotemcel for metachromatic leukodystrophy. [2023]

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

Safety of intrathecal delivery of recombinant human arylsulfatase A in children with metachromatic leukodystrophy: Results from a phase 1/2 clinical trial. [2021]

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

Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access. [2022]

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

Recent Advancements in the Diagnosis and Treatment of Leukodystrophies. [2021]

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

A retrospective cohort study of Libmeldy (atidarsagene autotemcel) for MLD: What we have accomplished and what opportunities lie ahead. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Leukodystrophies: a proposed classification system based on pathological changes and pathogenetic mechanisms. [2022]

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

Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation. [2019]