A Study to Evaluate the Pharmacodynamics, Safety, Tolerability, Pharmacokinetics, and Efficacy of RO7204239 in Participants with Facioscapulohumeral Muscular Dystrophy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

1 Dec 2022 → ongoing

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2022-503117-36-00

EudraCT number

2021-006255-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Others, Safety, Pharmacodynamic

To evaluate the pharmacodynamic (PD) effects of RO7204239 compared with placebo, using magnetic resonance imaging (MRI) and to evaluate the safety of RO7204239 compared with placebo

Secondary objectives 3

1. 1. To evaluate additional PD effects of RO7204239 compared to placebo, using serum samples and MRI
2. 2. To evaluate pharmacokinetics (PK) parameters for RO7204239
3. 3. To evaluate immune response to RO7204239

Conditions and MedDRA coding

Facioscapulohumeral muscular dystrophy (FSHD)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1. Age ≥ 18 and ≤ 65 years at the time of signing the Informed Consent Form
2. 2. Genetic confirmation of FSHD1 or FSHD2
3. 3. Clinical findings consistent with FSHD according to the investigator’s clinical judgment
4. 4. Ability to walk unassisted 10 meters (Timed 10-Meter Walk Test [10MWT])
5. 5. Ricci Clinical Severity Scale score ≥ 2.5 and ≤ 4
6. 6. Agreement to maintain the same frequency and intensity of physiotherapy, occupational therapy, and other forms of exercise during the clinical study

Exclusion criteria 6

1. 1. Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 17 months after the final dose of RO7204239
2. 2. Current or previous treatment (or receipt) of anti-myostatin therapies
3. 3. Treatment with any investigational therapy within 90 days prior to screening, or 5 drug-elimination half-lives of the drug, whichever is longer
4. 4. Contraindications to MRI scans, difficulties maintaining a prolonged supine position, or any other clinical history or examination finding that would pose a potential hazard in combination with MRI
5. 5. Presence of clinically significant ECG abnormalities from average of triplicate measurement at screening indicating a safety risk for participants
6. 6. Presence of clinically significant cardiovascular disease indicating a safety risk for participants. •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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. 1. Percent change from baseline in contractile muscle volume (CMV) of quadriceps femoris muscles, as assessed by MRI bilaterally
2. 2. Incidence, severity, and causal relationship of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0
3. 3. Change from baseline in vital signs, physical findings, ECG, echocardiogram, and clinical laboratory results
4. 4. Incidence of local and systemic injection reactions
5. 5. Incidence of abnormal laboratory findings
6. 6. Incidence of abnormal ECG parameters
7. 7. Incidence of abnormal echocardiographic parameters
8. 8. Incidence of abnormal vital signs

Secondary endpoints 16

1. 1. Change from baseline in serum concentrations of total and free latent myostatin, and mature myostatin
2. 2. Percent change from baseline in CMV of 36 muscles based on whole body MRI (excluding muscles with severe fat replacement)
3. 3. Change from baseline in fat fraction of 36 muscles based on whole body MRI (excluding muscles with severe fat replacement)
4. 4. Percent change from baseline in CMV of quadriceps femoris muscles, as assessed by MRI bilaterally
5. 5. Change from baseline in fat fraction of quadriceps femoris muscles, as assessed by MRI bilaterally
6. 6. Percent change from baseline in CMV of tibialis anterior muscles, as assessed by MRI bilaterally
7. 7. Change from baseline in fat fraction of tibialis anterior muscles, as assessed by MRI bilaterally
8. 8. Percent change from baseline in CMV of biceps brachii muscles, as assessed by MRI bilaterally
9. 9. Change from baseline in fat fraction of biceps brachii muscles, as assessed by MRI bilaterally
10. 10. Percent change from baseline in the contractile cross-sectional area (CSA) of skeletal muscle in the proximal lower limb muscles, as assessed by MRI bilaterally
11. 11. Change from baseline in the fat fraction of proximal lower limb muscles, as assessed at a single mid femur slice by MRI bilaterally
12. 12. Serum concentrations of RO7204239 at specified timepoints
13. 13. Cmax of RO7204239 at specified timepoints
14. 14. Area under the concentration-time curve (AUC) of RO7204239 at specified timepoints
15. 15. Ctrough of RO7204239 at specified timepoints
16. 16. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 10

Locations

2 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications