Biomarker Development in LGMD2i

Muscular Dystrophies Clinical Trial

— MLB-01-001  

Official title:

Biomarker Development in LGMD2i

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04202627
• Other study ID #: HM20018755
• Status: Completed
• Start date: December 1, 2019
• Est. completion date: October 10, 2022

Study information

• Verified date: March 2023
• Source: ML Bio Solutions, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The overall goal of this natural history study is to define the key LGMD2i phenotypes as measured by standard clinical outcome assessments (COAs), and to validate a muscle biomarker for LGMD2i to support therapeutic development.

Description:

Limb Girdle Muscular Dystrophy (LGMD) 2i is an autosomal recessive form of LGMD that is due to missense mutations in the Fukutin-related protein (FKRP) gene. Patients develop progressive proximal muscle weakness that leads to loss of ambulation. Patients will also commonly develop a cardiomyopathy and respiratory compromise.

There are promising new therapies that have been developed and as a result therapeutic trials are approaching.

The rationale for this study is to define appropriate COAs for LGMD2i, which will facilitate therapeutic development and ensure properly powered clinical trials. In addition, measurement of dystroglycan in muscles represents a potential muscle biomarker that could be used in early phase clinical trials as a measure of target engagement. The clinical utility of changes in dystroglycan has not been validated in human samples.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: October 10, 2022
• Est. primary completion date: October 10, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 10 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age between 10-65 at enrollment

• Clinically affected (defined as weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity)

• A genetically confirmed mutation in FKRP (LGMD2i)

• Willing and able to give informed consent and follow all procedures and requirements

Exclusion Criteria:

• Any other illness that would interfere with the ability to undergo safe testing or would interfere with interpretation of the results in the opinion of the site investigator.

• History of a bleeding disorder, platelet count <50,000, current use of an anticoagulant.

• Positive pregnancy test

• A 10-meter walk time of <4 seconds

Related Conditions & MeSH terms

• Limb Girdle Muscular Dystrophy
• Muscular Dystrophies

Locations

Country	Name	City	State
Denmark	Copenhagen Neuromuscular Center	Copenhagen
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Atrium Health	Charlotte	North Carolina
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	University of Florida	Gainesville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	University of California Irvine	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
ML Bio Solutions, Inc.	Virginia Commonwealth University

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To validate potential biomarkers	To develop a reliable measure of dystroglycosylation in human skeletal muscle by using fresh tissue biopsy.; A muscle biopsy will be collected at baseline and 6 months from the right tibialis anterior. The biopsy site will be uniform between investigators. The investigators will utilize a 14-gauge Supercore biopsy instrument to take a total of three aspirations from the same site.	Baseline, Month 6
Other	To understand the change from baseline in muscle mass using Magnetic Resonance Imaging	To understand the change from baseline in muscle mass using Magnetic Resonance Imaging	Baseline, Month 6, Month 12
Primary	10-Meter walk (10 MWT) -mobility	The 10 MWT will be used to determine the ambulatory Cohort for of all subjects. For the purposes of this study, the definitions for ambulation are as follows: Cohort A: completes the 10 MWT unaided in = 4 to = 12 seconds; Cohort B: completes the walk unaided in > 12 seconds or is non-ambulatory	Through study completion at 12 months
Primary	100-Meter Timed Test (100m) - mobility	The 100m timed test is designed to capture maximal ambulatory capacity. The participant will be asked to complete 4 full laps around 2 cones set 25 meters apart as quickly and as safely as possible, including running if able. This will not be assessed in participants with a 10-meter walk time greater than 12 seconds.	Through study completion at 12 months
Primary	NSAD- Motor performance	North Star Assessment for Dysferlinopathy (NSAD) is a functional scale specifically designed to measure motor performance in individuals with LGMD. It consists of 29 items that are considered clinically relevant items from the North Star Ambulatory Assessment and the Motor Function Measure 20 with a maximum score of 54 and higher scores indicate higher functional abilities.	Through study completion at 12 months
Primary	Timed up-and-go (TUG) - mobility	The TUG is an assessment used to evaluate functional ambulation, balance, and fall risk. The fastest time to rise from a chair, walk 3 meters, and return to sitting independently without an assistive device will be recorded. This will not be assessed in Cohort B participants.	Through study completion at 12 months
Primary	FVC - Pulmonary function	The total amount of air exhaled during the forced expiratory volume test (Forced vital capacity - FVC) will be assessed in a sitting position only.	Through study completion at 12 months
Primary	Timed 4 stair Climb (4SC) - mobility	The 4SC quantifies the time required for the participant to ascend 4 standard steps. This will not be assessed in participants with a 10 meter walk time greater than 12 seconds.	Through study completion at 12 months
Primary	9 Hole Peg Test (9HPT) - distal upper extremity function	The 9HPT is a quantitative measure of distal upper extremity function. It measures the time required for patients to place 9 pegs in the 9 holes on the board and then remove them as quickly as possible.	Through study completion at 12 months
Primary	Performance of Upper Limb (PUL 2.0) - limb function	The PUL is a tool designed for assessing upper limb function in persons with neuromuscular disorders. It was developed as a conceptual framework reflecting the progression of weakness and natural history of functional decline in Duchenne muscular dystrophy (DMD). There are 22 scored items; a score of 42 indicates the highest level of independent function and 0 the lowest.	Through study completion at 12 months
Primary	Hand Held Dynamometry (HHD) - isometric strength	HHD using the MicroFET2 myometer will be utilized to capture isometric strength in target muscle groups. Maximum strength in kilograms will be reported for each muscle group provided a continuous scale variable for analysis.	Through study completion at 12 months
Secondary	To develop clinical outcome assessments for LGMD2i	To determine the sensitivity of the COAs to longitudinal disease progression	Through study completion at 12 months