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A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy (MANOEUVRE)

Primary Purpose

Facioscapulohumeral Muscular Dystrophy (FSHD)

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Placebo
RO7204239
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Facioscapulohumeral Muscular Dystrophy (FSHD)

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Genetic confirmation of FSHD1 or FSHD2
  • Clinical findings consistent with FSHD
  • Ability to walk unassisted
  • Ricci Clinical Severity Scale score ≥ 2.5 and ≤ 4
  • Agreement to maintain the same frequency and intensity of physiotherapy, occupational therapy, and other forms of exercise during the clinical study

Exclusion Criteria:

  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 17 months after the final dose of RO7204239
  • Current or previous treatment (or receipt) of anti-myostatin therapies
  • Treatment with any investigational therapy within 90 days prior to screening, or 5 drug-elimination half-lives of the drug, whichever is longer
  • Contraindications to MRI scans
  • Presence of clinically significant ECG abnormalities
  • Presence of clinically significant cardiovascular disease
  • Presence of clinically significant abnormal findings in echocardiography at screening, with the exception of mitral valve prolapse, which does not exclude participants from the study
  • Any major illness within 1 month before screening
  • Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to RO7204239, or to the constituents of its formulation
  • History of malignancy (except in situ basal cell carcinoma of the skin and in situ carcinoma of the cervix of the uterus that have been excised and resolved with documented clean margins on pathology)
  • Any clinically relevant history of anaphylactic reaction requiring inotropic support
  • Any abnormal skin conditions, pigmentation, or lesions in the area intended for SC injection (abdomen) and that would prevent visualization of potential injection-site reactions to RO7204239
  • Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening or longer, if judged by the investigator that it may affect motor function assessment
  • Any planned surgery that may affect a participant's motor function assessment, including participants who have had surgery of scapular fixation within the 12 months preceding screening or that are planned during the study
  • Use of the following medications within 90 days prior to enrollment: salbutamol or another β2-adrenergic agonist taken orally; creatine; recombinant human growth hormone; recombinant human insulin growth factor-1; testosterone, oxandrolone, or other anabolic steroid; chronic oral or parenteral use of corticosteroids (inhaled corticosteroid use is allowed) unless required to manage injection reactions;agents anticipated to increase or decrease muscle volume or strength

Sites / Locations

  • Regents of the University of ColoradoRecruiting
  • University of Kansas Medical Center; Department of NeurologyRecruiting
  • Kennedy Krieger InstituteRecruiting
  • Virginia Commonwealth University Medical Center; Department of NeurologyRecruiting
  • Rigshospitalet; Klinik for Nerve- og MuskelsygdommeRecruiting
  • Policlinico Universitario Agostino Gemelli; UOC NeurologiaRecruiting
  • ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Centro clinico NEMO (NEuroMuscular Omnicentre)Recruiting
  • National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular DiseasesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

RO7204239

Arm Description

Participants will complete a 4-week pre-treatment period to collect baseline movement data with a wearable device, then receive subcutaneous (SC) placebo every 4 weeks for 52 weeks. After the treatment period, participants will have the option to receive RO7204239 for an additional 52 weeks.

Participants will complete a 4-week pre-treatment period to collect baseline movement data with a wearable device, then receive SC RO7204239 every 4 weeks for 52 weeks. After the treatment period, participants will have the option to receive RO7204239 for an additional 52 weeks.

Outcomes

Primary Outcome Measures

Percent change from baseline in contractile muscle volume (CMV) of quadriceps femoris muscles as assessed by magnetic resonance imaging (MRI) bilaterally
Percentage of participants with adverse events (AEs)

Secondary Outcome Measures

Change from baseline in serum concentration of total latent myostatin
Change from baseline in serum concentration of free latent myostatin
Change from baseline in serum concentration of mature myostatin
Percent change from baseline in CMV of 36 muscles based on whole body MRI
Change from baseline in fat fraction of 36 muscles based on whole body MRI
Percent change from baseline in CMV of quadriceps femoris muscles as assessed by MRI bilaterally
Change from baseline in fat fraction of quadriceps femoris muscles as assessed by MRI bilaterally
Percent change from baseline in CMV of tibialis anterior muscles as assessed by MRI bilaterally
Change from baseline in fat fraction of tibialis anterior muscles as assessed by MRI bilaterally
Percent change from baseline in CMV of biceps brachii muscles as assessed by MRI bilaterally
Change from baseline in fat fraction of biceps brachii muscles as assessed by MRI bilaterally
Percent change from baseline in contractile cross-sectional area (CSA) of skeletal muscle in the proximal lower limb muscles as assessed by MRI bilaterally
Change from baseline in fat fraction of proximal lower limb muscles as assessed at a single mid-femur slice bilaterally by MRI
Serum concentration of RO7204239
Maximum serum concentration (Cmax) of RO7204239
Area under the concentration-time curve (AUC) of RO7204239
Trough concentration (Ctrough) of RO7204239
Percentage of participants with anti-drug antibodies (ADAs)

Full Information

First Posted
September 16, 2022
Last Updated
October 9, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05548556
Brief Title
A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy
Acronym
MANOEUVRE
Official Title
A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate the Pharmacodynamics, Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 7, 2023 (Actual)
Primary Completion Date
June 15, 2024 (Anticipated)
Study Completion Date
December 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

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

5. Study Description

Brief Summary
The purpose of this study is to evaluate the pharmacodynamics, safety, tolerability, pharmacokinetics, and efficacy of RO7204239, a humanized monoclonal antibody that binds to human latent myostatin, in ambulant adult participants with facioscapulohumeral muscular dystrophy (FSHD).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Facioscapulohumeral Muscular Dystrophy (FSHD)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will complete a 4-week pre-treatment period to collect baseline movement data with a wearable device, then receive subcutaneous (SC) placebo every 4 weeks for 52 weeks. After the treatment period, participants will have the option to receive RO7204239 for an additional 52 weeks.
Arm Title
RO7204239
Arm Type
Experimental
Arm Description
Participants will complete a 4-week pre-treatment period to collect baseline movement data with a wearable device, then receive SC RO7204239 every 4 weeks for 52 weeks. After the treatment period, participants will have the option to receive RO7204239 for an additional 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive subcutaneous (SC) placebo every 4 weeks (Q4W)
Intervention Type
Drug
Intervention Name(s)
RO7204239
Intervention Description
Participants will receive SC RO7204239 Q4W
Primary Outcome Measure Information:
Title
Percent change from baseline in contractile muscle volume (CMV) of quadriceps femoris muscles as assessed by magnetic resonance imaging (MRI) bilaterally
Time Frame
Week 52
Title
Percentage of participants with adverse events (AEs)
Time Frame
Up to 2.5 years
Secondary Outcome Measure Information:
Title
Change from baseline in serum concentration of total latent myostatin
Time Frame
Through 2 years
Title
Change from baseline in serum concentration of free latent myostatin
Time Frame
Through 2 years
Title
Change from baseline in serum concentration of mature myostatin
Time Frame
Through 2 years
Title
Percent change from baseline in CMV of 36 muscles based on whole body MRI
Time Frame
Weeks 28 and 52
Title
Change from baseline in fat fraction of 36 muscles based on whole body MRI
Time Frame
Weeks 28 and 52
Title
Percent change from baseline in CMV of quadriceps femoris muscles as assessed by MRI bilaterally
Time Frame
Week 28
Title
Change from baseline in fat fraction of quadriceps femoris muscles as assessed by MRI bilaterally
Time Frame
Weeks 28 and 52
Title
Percent change from baseline in CMV of tibialis anterior muscles as assessed by MRI bilaterally
Time Frame
Weeks 28 and 52
Title
Change from baseline in fat fraction of tibialis anterior muscles as assessed by MRI bilaterally
Time Frame
Weeks 28 and 52
Title
Percent change from baseline in CMV of biceps brachii muscles as assessed by MRI bilaterally
Time Frame
Weeks 28 and 52
Title
Change from baseline in fat fraction of biceps brachii muscles as assessed by MRI bilaterally
Time Frame
Weeks 28 and 52
Title
Percent change from baseline in contractile cross-sectional area (CSA) of skeletal muscle in the proximal lower limb muscles as assessed by MRI bilaterally
Time Frame
Weeks 28 and 52
Title
Change from baseline in fat fraction of proximal lower limb muscles as assessed at a single mid-femur slice bilaterally by MRI
Time Frame
Weeks 28 and 52
Title
Serum concentration of RO7204239
Time Frame
Through 2 years
Title
Maximum serum concentration (Cmax) of RO7204239
Time Frame
Through 2 years
Title
Area under the concentration-time curve (AUC) of RO7204239
Time Frame
Through 2 years
Title
Trough concentration (Ctrough) of RO7204239
Time Frame
Through 2 years
Title
Percentage of participants with anti-drug antibodies (ADAs)
Time Frame
Baseline up to approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Genetic confirmation of FSHD1 or FSHD2 Clinical findings consistent with FSHD Ability to walk unassisted Ricci Clinical Severity Scale score ≥ 2.5 and ≤ 4 Agreement to maintain the same frequency and intensity of physiotherapy, occupational therapy, and other forms of exercise during the clinical study Exclusion Criteria: Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 17 months after the final dose of RO7204239 Current or previous treatment (or receipt) of anti-myostatin therapies Treatment with any investigational therapy within 90 days prior to screening, or 5 drug-elimination half-lives of the drug, whichever is longer Contraindications to MRI scans Presence of clinically significant ECG abnormalities Presence of clinically significant cardiovascular disease Presence of clinically significant abnormal findings in echocardiography at screening, with the exception of mitral valve prolapse, which does not exclude participants from the study Any major illness within 1 month before screening Ascertained or presumptive hypersensitivity (e.g., anaphylactic reaction) to RO7204239, or to the constituents of its formulation History of malignancy (except in situ basal cell carcinoma of the skin and in situ carcinoma of the cervix of the uterus that have been excised and resolved with documented clean margins on pathology) Any clinically relevant history of anaphylactic reaction requiring inotropic support Any abnormal skin conditions, pigmentation, or lesions in the area intended for SC injection (abdomen) and that would prevent visualization of potential injection-site reactions to RO7204239 Immobilization, surgical procedures, fracture, or trauma to the upper or lower limbs within 90 days prior to screening or longer, if judged by the investigator that it may affect motor function assessment Any planned surgery that may affect a participant's motor function assessment, including participants who have had surgery of scapular fixation within the 12 months preceding screening or that are planned during the study Use of the following medications within 90 days prior to enrollment: salbutamol or another β2-adrenergic agonist taken orally; creatine; recombinant human growth hormone; recombinant human insulin growth factor-1; testosterone, oxandrolone, or other anabolic steroid; chronic oral or parenteral use of corticosteroids (inhaled corticosteroid use is allowed) unless required to manage injection reactions;agents anticipated to increase or decrease muscle volume or strength
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: BN43703 https://forpatients.roche.com/
Phone
888-662-6728
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Regents of the University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Kansas Medical Center; Department of Neurology
City
Fairway
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Recruiting
Facility Name
Kennedy Krieger Institute
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Individual Site Status
Recruiting
Facility Name
Virginia Commonwealth University Medical Center; Department of Neurology
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0599
Country
United States
Individual Site Status
Recruiting
Facility Name
Rigshospitalet; Klinik for Nerve- og Muskelsygdomme
City
København Ø
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Name
Policlinico Universitario Agostino Gemelli; UOC Neurologia
City
Roma
State/Province
Lazio
ZIP/Postal Code
00168
Country
Italy
Individual Site Status
Recruiting
Facility Name
ASST GRANDE OSPEDALE METROPOLITANO NIGUARDA; Centro clinico NEMO (NEuroMuscular Omnicentre)
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20162
Country
Italy
Individual Site Status
Recruiting
Facility Name
National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
City
London
ZIP/Postal Code
WC1 3BG
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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A Study to Evaluate RO7204239 in Participants With Facioscapulohumeral Muscular Dystrophy

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