GDNF Gene Therapy for Multiple System Atrophy

Sponsor

Brain Neurotherapy Bio, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04680065

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The objective of this randomized, double-blinded, placebo-controlled Phase 1 investigation is to evaluate the safety and potential clinical effect of AAV2-GDNF delivered to the putamen in subjects with either a possible or probable diagnosis of Multiple System Atrophy.

Condition or Disease	Intervention/Treatment	Phase
Multiple System Atrophy	Biological: AAV2-GDNF gene therapy Procedure: Sham (Placebo) Surgery	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

9 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Up to 9 study participants meeting eligibility criteria will be randomized in a 2:1 fashion to receive either the investigational medicinal product or sham surgery in this Phase 1 trial.Up to 9 study participants meeting eligibility criteria will be randomized in a 2:1 fashion to receive either the investigational medicinal product or sham surgery in this Phase 1 trial.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Randomized, Double-Blind, Placebo-controlled Safety Study of Glial Cell Line-Derived Neurotrophic Factor Gene Transfer (AAV2-GDNF) in Multiple System Atrophy

Anticipated Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Treatment	Biological: AAV2-GDNF gene therapy Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose
Sham Comparator: Placebo Surgery	Procedure: Sham (Placebo) Surgery Bilateral partial burr/twist holes without dural penetration

Arm

Intervention/Treatment

Experimental: Active Treatment

Biological: AAV2-GDNF gene therapy

Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose

Sham Comparator: Placebo Surgery

Procedure: Sham (Placebo) Surgery

Bilateral partial burr/twist holes without dural penetration

Outcome Measures

Primary Outcome Measures

The incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) assessed clinically by physical and neurological examinations [3 years]
Number of TEAE and SAE's reported post-treatment.

Secondary Outcome Measures

MSA symptoms/signs as assessed by the Unified Multiple System Atrophy Rating Scale (UMSARS) [12 months]
Change from baseline in the Unified Multiple System Atrophy Rating Scale (UMSARS) and compared to placebo. UMSARS total scores range from 0-104 points with higher scores indicating greater severity of impairment.
Change in striatal dopamine transporter binding as measured by [123-I] Ioflupane [12 months]
Percent and absolute change in ratio of specific to non-specific binding of 123I FP-CIT to DaT from baseline and compared to placebo by Single Photon Emission Computed Tomography (SPECT) dopamine transporter (DaT) imaging
Change in the quality of life as measured by Multiple System Atrophy Quality of Life (MSA-QoL) [12 months]
Change from baseline and compared to placebo in the Multiple System Atrophy Quality of Life (MSA-QoL) scale. MSA-QoL is a self-reported questionnaire that measures MSA impact in day to day activities. Scale consists of 40 items with a five response option format (0 - no problem to 4 extreme problem) and a "not applicable" response option.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male and female adults 35-75 years of age (inclusive)
Diagnosed with MSA with sporadic, adult-onset (>30 yo) with predominant parkinsonian symptoms
Less than 4 years from clinical diagnosis of MSA with expected survival > 3 years
Stable medication regimen
Ability to walk with or without an assistive device

Exclusion Criteria:

Presence of idiopathic Parkinson's disease or other neurological diseases
Myocardial sympathetic denervation inconsistent with an MSA diagnosis
Presence of dementia, psychosis, substance abuse or poorly controlled depression
Prior brain surgery (i.e. deep brain stimulator) or other brain imaging abnormalities
Receiving an investigational drug
History of cancer or poorly controlled medical conditions that would increase surgical risk
Inability to tolerate laying flat in an MRI or allergy to gadolinium