PCSK9 Inhibitor Treatment for Patients With SPG5

NCT04101643 | Unknown Phase 1 DMC

• 1 other identifier: MRCTA, ECFAHofFMU[2019]209
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Spastic paraplegia type 5 (SPG5) is a rare subtype of hereditary spastic paraplegia, a highly heterogeneous group of neurodegenerative disorders defined by progressive neurodegeneration of the corticospinal tract motor neurons. SPG5 is caused by recessive mutations in the gene CYP7B1 encoding oxysterol-7a-hydroxylase. This enzyme is involved in the degradation of cholesterol into primary bile acids. CYP7B1 deficiency has been shown to lead to accumulation of neurotoxic oxysterols. Oxysterols were found to impair metabolic activity and viability of human cortical neurons at concentrations found in SPG5 patients, indicating that elevated levels of oxysterols might be key pathogenic factors in SPG5. Monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) have emerged as a new class of drugs that effectively lower cholesterol levels. Evolocumab, a member of this class, is a fully human monoclonal antibody that reduces LDL cholesterol levels by approximately 60%. We thus performed this interventional trial with Evolocumab 420 mg for SPG5 patients.

Conditions

Hereditary Spastic Paraplegia Type 5

Outcome Measures

Primary Outcomes (1)

• The change of 27-hydroxycholesterol (27-OHC)

  Cholesterol is initially side chain oxidized and the resulting 27-hydroxycholesterol (27-OHC) are 7a-hydroxylated

  up to 4 weeks

Study Arms (1)

Evolocumab group

EXPERIMENTAL

Eligible patients receive subcutaneous injections of evolocumab 420 mg

Drug: evolocumab

Interventions

evolocumab DRUG

Eligible patients receive subcutaneous injections of evolocumab 420 mg

Evolocumab group

Eligibility Criteria

• Age: 14 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 14-80 years
• Probands with clinically manifest hereditary spastic paraplegia
• Genetically confirmed diagnosis of SPG5

You may not qualify if:

• Comprised treatment with statins 3 months prior to enrolment
• Contraindications to PCSK9 inhibitor therapy
• Pregnancy was excluded in women of childbearing age

Sponsors & Collaborators

• First Affiliated Hospital of Fujian Medical University: lead

Study Sites (1)

Department of Neurology , First Affiliated Hospital Fujian Medical University

Fuzhou, China

RECRUITING

MeSH Terms

Interventions

evolocumab

Study Officials

• Wan-Jin Chen

  First Affiliated Hospital Fujian Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ying Fu

CONTACT

13920263588; fuying1995@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neurology department

Study Record Dates

• First Submitted: September 22, 2019
• First Posted: September 24, 2019
• Study Start: September 29, 2019
• Primary Completion: January 3, 2023
• Study Completion: January 3, 2023
• Last Updated: November 23, 2021

Record last verified: 2021-11

Locations

CN (1)