GDNF Gene Therapy for Multiple System Atrophy

• ClinicalTrials.gov Identifier: NCT04680065
• Recruitment Status: Recruiting
• First Posted: December 22, 2020
• Last Update Posted: April 9, 2024
• Sponsor: Brain Neurotherapy Bio, Inc.
• Information provided by (Responsible Party): Brain Neurotherapy Bio, Inc.

Tracking Information

• First Submitted Date: December 15, 2020
• First Posted Date: December 22, 2020
• Last Update Posted Date: April 9, 2024
• Actual Study Start Date: October 3, 2023
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 20, 2020)

The incidence of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) assessed clinically by physical and neurological examinations [ Time Frame: 3 years ]

Number of TEAE and SAE's reported post-treatment.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 20, 2020)

• MSA symptoms/signs as assessed by the Unified Multiple System Atrophy Rating Scale (UMSARS) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

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.

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Multiple System Atrophy

Intervention

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

Study Arms

• Experimental: Active Treatment
  Intervention: Biological: AAV2-GDNF gene therapy
• Sham Comparator: Placebo Surgery
  Intervention: Procedure: Sham (Placebo) Surgery

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 20, 2020): 9
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2028
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Akash Pandhare, MD; 336-265-2790; askfirst@askbio.com

Contact: Christian Urrea, MD; 336-265-2790; askfirst@askbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04680065
• Other Study ID Numbers: MSA-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Brain Neurotherapy Bio, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Brain Neurotherapy Bio, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Brain Neurotherapy Bio, Inc.
• Verification Date: April 2024