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GDNF Gene Therapy for Multiple System Atrophy

Primary Purpose

Multiple System Atrophy

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AAV2-GDNF gene therapy
Sham (Placebo) Surgery
Sponsored by
Brain Neurotherapy Bio, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple System Atrophy focused on measuring MSA, Multiple System Atrophy, Neurotrophic factor, Growth factor, Glial cell line-derived neurotrophic factor, GDNF, AAV, Gene therapy

Eligibility Criteria

35 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

  • University of California IrvineRecruiting
  • Massachusetts General Hospital
  • Quest Research InstituteRecruiting
  • The Ohio State University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active Treatment

Placebo Surgery

Arm Description

Outcomes

Primary Outcome Measures

The incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) assessed clinically by physical and neurological examinations
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)
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
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)
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.

Full Information

First Posted
December 15, 2020
Last Updated
October 13, 2023
Sponsor
Brain Neurotherapy Bio, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04680065
Brief Title
GDNF Gene Therapy for Multiple System Atrophy
Official Title
Randomized, Double-Blind, Placebo-controlled Safety Study of Glial Cell Line-Derived Neurotrophic Factor Gene Transfer (AAV2-GDNF) in Multiple System Atrophy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 3, 2023 (Actual)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Brain Neurotherapy Bio, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple System Atrophy
Keywords
MSA, Multiple System Atrophy, Neurotrophic factor, Growth factor, Glial cell line-derived neurotrophic factor, GDNF, AAV, Gene therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Treatment
Arm Type
Experimental
Arm Title
Placebo Surgery
Arm Type
Sham Comparator
Intervention Type
Biological
Intervention Name(s)
AAV2-GDNF gene therapy
Intervention Description
Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose
Intervention Type
Procedure
Intervention Name(s)
Sham (Placebo) Surgery
Intervention Description
Bilateral partial burr/twist holes without dural penetration
Primary Outcome Measure Information:
Title
The incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) assessed clinically by physical and neurological examinations
Description
Number of TEAE and SAE's reported post-treatment.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
MSA symptoms/signs as assessed by the Unified Multiple System Atrophy Rating Scale (UMSARS)
Description
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.
Time Frame
12 months
Title
Change in striatal dopamine transporter binding as measured by [123-I] Ioflupane
Description
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
Time Frame
12 months
Title
Change in the quality of life as measured by Multiple System Atrophy Quality of Life (MSA-QoL)
Description
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.
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male and female 35-75 years of age (inclusive) Clinical diagnosis of MSA, parkinsonian type with symptoms onset sporadic, progressive and > 30 years of age Less than 5 years from MSA parkinsonian diagnosis with expected survival more than 3 years Stable anti-parkinsonian medication regimen Ability to walk a distance of 25 feet with or without an assistive device Exclusion Criteria: Presence of idiopathic Parkinson's disease (PD) or any PD-related mutation or other neurological diseases Presence of dementia, psychosis, substance abuse or poorly controlled depression Prior brain surgery (i.e., deep brain stimulator implantation) or other brain imaging abnormalities History of cancer or poorly controlled medical conditions that would increase surgical risk Received investigational agent within 12 weeks Inability to tolerate laying flat in an MRI and/or allergy to gadolinium NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Akash Pandhare, MD
Phone
336-265-2790
Email
askfirst@askbio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Christian Urrea, MD
Phone
336-265-2790
Email
askfirst@askbio.com
Facility Information:
Facility Name
University of California Irvine
City
Irvine
State/Province
California
ZIP/Postal Code
92697
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Email
GDNFMSA@hs.uci.edu
First Name & Middle Initial & Last Name & Degree
Nicolas Phielipp, MD
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Active, not recruiting
Facility Name
Quest Research Institute
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Renee Najor
Email
Renee.Najor@questri.com
First Name & Middle Initial & Last Name & Degree
Aaron Ellenbogen, DO
Facility Name
The Ohio State University Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Active, not recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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GDNF Gene Therapy for Multiple System Atrophy

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