NCT04101643

PCSK9 Inhibitor Treatment for Patients With SPG5

Status unknown Phase 1, PHASE2 Last updated 23 November 2021

What this trial tests

Phase 1, PHASE2 trial testing evolocumab in Hereditary Spastic Paraplegia Type 5 in 30 participants. Status unknown.

Timeline

29 September 2019

Primary endpoint
3 January 2023

3 January 2023

Quick facts

Lead sponsor	First Affiliated Hospital of Fujian Medical University
Phase	Phase 1, PHASE2
Status	Status unknown
Study type	INTERVENTIONAL
Allocation	na
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	29 September 2019
Primary completion	3 January 2023
Estimated completion	3 January 2023
Sites	1 location across China

Drugs / interventions tested

• evolocumab (EVOLOCUMAB) — full drug profile →

Conditions studied

• Hereditary Spastic Paraplegia Type 5 — all drugs for Hereditary Spastic Paraplegia Type 5 →

Sponsor

First Affiliated Hospital of Fujian Medical University

Who can join

Adults 14 to 80, any sex, with Hereditary Spastic Paraplegia Type 5. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Childhood-onset hereditary spastic paraplegia and its treatable mimics.
   Ebrahimi-Fakhari D, Saffari A, Pearl PL. · · 2022 · cited 18× · PMID 34183250 · DOI 10.1016/j.ymgme.2021.06.006