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Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I) (Fortify)

Primary Purpose

Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I)

Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BBP-418 (ribitol)
Placebo
Sponsored by
ML Bio Solutions, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I)

Eligibility Criteria

12 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Participants must meet all the following criteria to be enrolled: Have a genetically confirmed diagnosis of LGMD2I/R9 (including review of records of previous molecular genetic testing) and be clinically affected (defined as demonstrating clinical weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity). Male or female participants 12 to 60 years of age (inclusive). Have a body weight >30 kg. The participant (or parent/guardian) who signs the ICF understands the study procedures and the participant agrees to participate in the study by giving informed consent (and assent, if <18 years of age). Female participants of childbearing potential and male participants of reproductive potential must be willing to use a highly effective method of contraception from time of consent through 12 weeks after last dose. Willing and able to complete all study procedures, including biopsies, according to the Schedule of Assessments (see Appendix 1). Participants must not meet any of the following criteria to be enrolled: Evidence of clinically significant concomitant disease, including: Any significant concomitant medical condition, including mental, cardiac, renal, pulmonary, hepatic, or endocrine disease other than that associated with LGMD2I/R9. Moderate to severe renal impairment (estimated glomerular filtration rate [eGFR] of < 60 mL/min/1.73 m2 based on cystatin C [CysC]), as calculated by the central laboratory. Any other laboratory, vital sign, ECG abnormality, clinical history, or finding that, in the Investigator's opinion, is likely to unfavorably alter the risk-benefit of study participation, confound study results, or interfere with study conduct or compliance. Surgery for scoliosis or other indication that will significantly impact the participant's ability to execute clinical assessments planned or expected to be required to manage curvature within 12 months following the Screening Visit. A participant with a score of zero on any one or more of the primary or key secondary endpoints at the time of screening. (Participants who previously completed participation in Study MLB-01-001 and would be excluded due to this criterion may enroll in this study provided all inclusion and no other exclusion criteria are met.) If pregnant and/or breastfeeding or planning to conceive children within the projected duration of the study through 12 weeks after the last dose of study treatment. Use of ribose or other sugar alcohol-containing supplement within 90 days of the Screening Visit. Use of a systemic corticosteroid for the treatment of muscular dystrophy within 90 days of the Screening Visit. (An inhaled corticosteroid or bronchodilator for reactive airway disease is allowed if the participant is on a stable dose for 30 days prior to study entry.) Previously received gene therapy to treat LGMD2I/R9. Participants with active suicidal ideation as measured by Columbia-Suicide Severity Rating Scale during screening with most severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent). Presence of a platelet disorder, bleeding disorder, or other contraindication to muscle biopsy. Actively on an experimental therapy or device or was on an experimental therapy or device within 90 days of the Screening Visit. In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the participant's safety, increase their risk from participation, or interfere with the study. For COVID-19 infections, Investigator should refer to local guidance.

Sites / Locations

  • University of California IrvineRecruiting
  • University of Colorado Anschutz Medical CampusRecruiting
  • University of Florida
  • University of IowaRecruiting
  • University of Kansas Medical Center
  • Kennedy Krieger InstituteRecruiting
  • University of Minnesota, Twin CitiesRecruiting
  • Washington University School of MedicineRecruiting
  • Oregon Health & Science University (OHSU) - Neurology Clinic - South Waterfront
  • Penn State
  • The Children's Hospital of PhiladelphiaRecruiting
  • University of PennsylvaniaRecruiting
  • Royal Brisbane and Women's Hospital,
  • Rigshospitalet, Neuromuscular Clinic and Research Unit
  • University Hospital Essen
  • IRCCS Ca' Granda Ospedale
  • Leiden University Medical Center
  • Universitetssykehuset Nord-Norge, Department of Neurology
  • Great Ormond Street Hospital for Children
  • International Centre for Life

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

BBP-418

Placebo to Match BBP-418

Arm Description

BBP-418 Granules for Oral Solution will be supplied as granules in tri-ply PET/Aluminum/PE sachets for unit dose. The number of sachets to reconstitute will depend on the applicable dose to be delivered, 9 g BID or 12 g BID, as determined by the weight of the participant. The granules will be reconstituted in water for oral administration.

The placebo will be identical to the BBP-418 Granules for Oral Solution in appearance, packaging, labeling, and storage conditions.

Outcomes

Primary Outcome Measures

Change from baseline in North Star Assessment for Limb Girdle Muscular Dystrophy following 36 months of treatment to assess efficacy of BBP-418 or placebo
Frequency and severity of treatment-emergent adverse events following 36 months of treatment to assess safety of BBP-418 or placebo

Secondary Outcome Measures

Change from baseline in 10 meter walk test velocity to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Change from baseline in pulmonary function as measured by FVC (percent predicted, performed in a sitting position) to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Change from baseline in the Performance of Upper Limb scale 2.0 to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9

Full Information

First Posted
February 16, 2023
Last Updated
October 17, 2023
Sponsor
ML Bio Solutions, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05775848
Brief Title
Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)
Acronym
Fortify
Official Title
A Phase 3 Randomized, Placebo-controlled, Double-blind Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 31, 2023 (Actual)
Primary Completion Date
July 2027 (Anticipated)
Study Completion Date
July 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ML Bio Solutions, 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
This study will evaluate the safety and efficacy of long-term administration of BBP-418 in patients with LGMD2I/R9. The study will include patients ages 12 to 60, consistent with the existing preclinical toxicology profile. This will encompass the significant majority of existing diagnosed patients based upon the established epidemiology of the disease.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Limb-Girdle Muscular Dystrophy Type 2I (LGMD2I)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomization will be stratified by mutation status (L276I homozygous or other), age (<12 years [to allow for possible addition of this age group in a future protocol amendment], 12 to <18 years, and 18 to 60 years of age), and qualification status for the Primary Efficacy Analysis Population ("qualifies" or "does not qualify").
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
2:1 Randomization
Allocation
Randomized
Enrollment
81 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
BBP-418
Arm Type
Active Comparator
Arm Description
BBP-418 Granules for Oral Solution will be supplied as granules in tri-ply PET/Aluminum/PE sachets for unit dose. The number of sachets to reconstitute will depend on the applicable dose to be delivered, 9 g BID or 12 g BID, as determined by the weight of the participant. The granules will be reconstituted in water for oral administration.
Arm Title
Placebo to Match BBP-418
Arm Type
Placebo Comparator
Arm Description
The placebo will be identical to the BBP-418 Granules for Oral Solution in appearance, packaging, labeling, and storage conditions.
Intervention Type
Drug
Intervention Name(s)
BBP-418 (ribitol)
Intervention Description
The BBP-418 drug product is provided as Granules for Oral solution consisting of BBP-418 drug substance and silicon dioxide in a multilaminate sachet with a foil barrier. Silicon dioxide is generally regarded as safe and listed in the FDA IIAD. Silicon dioxide is a compendial excipient and is commonly used in pharmaceutical dosage forms. The BBP-418 Granules for Oral Solution are provided in sachets to provide 3 g BBP-418 per sachet. The BBP-418 Granules for Oral Solution are reconstituted in water for oral administration.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
A placebo matched for similar taste and appearance was compounded at the clinical pharmacy with sucralose as a 0.35 mg/mL oral solution in purified water (USP) in a glass container. Sucralose is similar in taste to the compounded drug product.
Primary Outcome Measure Information:
Title
Change from baseline in North Star Assessment for Limb Girdle Muscular Dystrophy following 36 months of treatment to assess efficacy of BBP-418 or placebo
Time Frame
36 months
Title
Frequency and severity of treatment-emergent adverse events following 36 months of treatment to assess safety of BBP-418 or placebo
Time Frame
36 months
Secondary Outcome Measure Information:
Title
Change from baseline in 10 meter walk test velocity to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Time Frame
36 months
Title
Change from baseline in pulmonary function as measured by FVC (percent predicted, performed in a sitting position) to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Time Frame
36 months
Title
Change from baseline in the Performance of Upper Limb scale 2.0 to assess the clinical efficacy of BBP-418 in patients with LGMD2I/R9
Time Frame
36 months
Other Pre-specified Outcome Measures:
Title
Change from baseline in total glycosylated Alpha dystroglycan to assess biomarkers for clinical efficacy of BBP-418 in patients with LGMD2I/R9
Time Frame
36 months
Title
Change from baseline in glycosylated Alpha dystroglycan / total glycosylated Alpha dystroglycan ratio to assess biomarkers for clinical efficacy of BBP-418 in patients with LGMD2I/R9
Time Frame
36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Participants must meet all the following criteria to be enrolled: Have a genetically confirmed diagnosis of LGMD2I/R9 (including review of records of previous molecular genetic testing) and be clinically affected (defined as demonstrating clinical weakness on bedside evaluation in either a limb-girdle pattern, or in a distal extremity). Male or female participants 12 to 60 years of age (inclusive). Have a body weight >30 kg. The participant (or parent/guardian) who signs the ICF understands the study procedures and the participant agrees to participate in the study by giving informed consent (and assent, if <18 years of age). Female participants of childbearing potential and male participants of reproductive potential must be willing to use a highly effective method of contraception from time of consent through 12 weeks after last dose. Willing and able to complete all study procedures, including biopsies, according to the Schedule of Assessments (see Appendix 1). Participants must not meet any of the following criteria to be enrolled: Evidence of clinically significant concomitant disease, including: Any significant concomitant medical condition, including mental, cardiac, renal, pulmonary, hepatic, or endocrine disease other than that associated with LGMD2I/R9. Moderate to severe renal impairment (estimated glomerular filtration rate [eGFR] of < 60 mL/min/1.73 m2 based on cystatin C [CysC]), as calculated by the central laboratory. Any other laboratory, vital sign, ECG abnormality, clinical history, or finding that, in the Investigator's opinion, is likely to unfavorably alter the risk-benefit of study participation, confound study results, or interfere with study conduct or compliance. Surgery for scoliosis or other indication that will significantly impact the participant's ability to execute clinical assessments planned or expected to be required to manage curvature within 12 months following the Screening Visit. A participant with a score of zero on any one or more of the primary or key secondary endpoints at the time of screening. (Participants who previously completed participation in Study MLB-01-001 and would be excluded due to this criterion may enroll in this study provided all inclusion and no other exclusion criteria are met.) If pregnant and/or breastfeeding or planning to conceive children within the projected duration of the study through 12 weeks after the last dose of study treatment. Use of ribose or other sugar alcohol-containing supplement within 90 days of the Screening Visit. Use of a systemic corticosteroid for the treatment of muscular dystrophy within 90 days of the Screening Visit. (An inhaled corticosteroid or bronchodilator for reactive airway disease is allowed if the participant is on a stable dose for 30 days prior to study entry.) Previously received gene therapy to treat LGMD2I/R9. Participants with active suicidal ideation as measured by Columbia-Suicide Severity Rating Scale during screening with most severe suicide ideation score of 4 (Active Suicidal Ideation with Some Intent to Act, without Specific Plan) or 5 (Active Suicidal Ideation with Specific Plan and Intent). Presence of a platelet disorder, bleeding disorder, or other contraindication to muscle biopsy. Actively on an experimental therapy or device or was on an experimental therapy or device within 90 days of the Screening Visit. In the judgment of the Investigator or Medical Monitor, has any clinically important ongoing medical condition or laboratory abnormality or condition that might jeopardize the participant's safety, increase their risk from participation, or interfere with the study. For COVID-19 infections, Investigator should refer to local guidance.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ML Bio Soultions Patient Information
Phone
(646) 659-6642
Email
info@mlbiosolutions.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:
First Name & Middle Initial & Last Name & Degree
Tahseen Mozaffar, MD
Phone
714-509-4867
Email
mozaffar@hs.uci.edu
First Name & Middle Initial & Last Name & Degree
Mozaffar Tasheen, MD
Facility Name
University of Colorado Anschutz Medical Campus
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Ragole, MD
Phone
303-724-4644
Email
NeuroResearch@cuanschutz.edu
First Name & Middle Initial & Last Name & Degree
Thomas Ragole, MD
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carla Zingariello, MD
Phone
352-273-8687
Email
czingariello@ufl.edu
First Name & Middle Initial & Last Name & Degree
Yara Mohamed
Phone
(352) 294-8962
Email
yaramohamed@peds.ufl.edu
First Name & Middle Initial & Last Name & Degree
Carla Zingariello, MD
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathryn Mathews, MD
Phone
319-356-7726
Email
Katherine-Mathews@uiowa.edu
First Name & Middle Initial & Last Name & Degree
Kathryn Mathews, MD
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jeffrey Statland, MD
Phone
913-945-9933
Email
jstatland@kumc.edu
First Name & Middle Initial & Last Name & Degree
Jeffrey Statland, MD
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Doris Leung, MD
Phone
443-923-9525
Email
LeungD@kennedykrieger.org
First Name & Middle Initial & Last Name & Degree
Doris Leung, MD
Facility Name
University of Minnesota, Twin Cities
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Kang, MD
Phone
612-626-7038
Email
pkang@umn.edu
First Name & Middle Initial & Last Name & Degree
Peter Kang
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olivia Money
Phone
314-273-7807
Email
moneyo@wustl.edu
First Name & Middle Initial & Last Name & Degree
Conrad Weihl, MD
Facility Name
Oregon Health & Science University (OHSU) - Neurology Clinic - South Waterfront
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Diana Dimitrov, PhD
Phone
503-494-7269
Email
dimitrov@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Nizar Chahin, MD
Email
chahin@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Nizar Chahin, MD
Facility Name
Penn State
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mansoureh Mamarabadi, MD
Phone
717-531-3828
Email
mmamarabadi@pennstatehealth.psu.edu
First Name & Middle Initial & Last Name & Degree
Mansoureh Mamarabadi, MD
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Brandsema, MD
Phone
215-590-1719
Email
BrandsemaJ@chop.edu
First Name & Middle Initial & Last Name & Degree
John Brandsema
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lauren Elman, MD
Phone
215-829-6708
Email
lauren.elman@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Lauren Elman, MD
Facility Name
Royal Brisbane and Women's Hospital,
City
Brisbane
State/Province
Queensland
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kate Thorpe, MD
Phone
36460016
Email
Kathryn.thorpe@health.qld.gov.au
First Name & Middle Initial & Last Name & Degree
Robert Henderson
Facility Name
Rigshospitalet, Neuromuscular Clinic and Research Unit
City
Copenhagen
Country
Denmark
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Vissing, Prof, MD
Phone
+45 35452562
Email
john.vissing@regionh.dk
First Name & Middle Initial & Last Name & Degree
John Vissing, Prof, MD
Facility Name
University Hospital Essen
City
Essen
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea Gangfuss, MD
First Name & Middle Initial & Last Name & Degree
Andrea Gangfuss, MD
Facility Name
IRCCS Ca' Granda Ospedale
City
Milan
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giacomo Comi, Prof, MD
Phone
390255033801
Email
giacomo.comi@unimi.it
First Name & Middle Initial & Last Name & Degree
Giacomo Comi, MD
Facility Name
Leiden University Medical Center
City
Leiden
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Erik Niks, MD
First Name & Middle Initial & Last Name & Degree
Erik Niks, MD
Facility Name
Universitetssykehuset Nord-Norge, Department of Neurology
City
Tromsø
Country
Norway
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kjell Arne Arntzen, PhD, MD
Email
Kjell.arne.arntzen@unn.no
First Name & Middle Initial & Last Name & Degree
Kjell Arne Arntzen, PhD, MD
Facility Name
Great Ormond Street Hospital for Children
City
London
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Baranello, MD
First Name & Middle Initial & Last Name & Degree
Giovanni Baranello, MD
Facility Name
International Centre for Life
City
Newcastle Upon Tyne
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Volker Straub, Prof, MD
Phone
441912418610
Email
nmd.clinicaltrials@newcastle.ac.uk
First Name & Middle Initial & Last Name & Degree
Volker Straub, Prof MD

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

Study to Evaluate the Efficacy and Safety of BBP-418 (Ribitol) in Patients With Limb Girdle Muscular Dystrophy 2I (LGMD2I)

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