Clinical trial • Phase III • Musculoskeletal

Humanised IgG1 monoclonal antibody against TfR1 conjugated to double stranded siRNA oligonucleotide against DUX4 mRNA via a non-cleavable linker for Facioscapulohumeral muscular dystrophy (FSHD)

Phase III trial of Humanised IgG1 monoclonal antibody against TfR1 conjugated to double stranded siRNA oligonucleotide against DUX4 mRNA via a non-cleavab…

Overview

Trial Therapeutic Area
Musculoskeletal
Trial Disease
Facioscapulohumeral muscular dystrophy (FSHD)
Trial Stage
Phase III
Drug Modality
Monoclonal antibody | Oligonucleotide
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
10-07-2025
First CTIS Authorization Date
04-11-2025

Trial design

Randomised, 0.9% saline for iv administration (placebo)-controlled Phase III trial in Italy, France, Spain and others.

Randomised
Yes
Comparator
0.9% Saline for IV administration (placebo)
Target Sample Size
120
Trial Duration For Participant
546

Eligibility

Recruits 120 The protocol indicates vulnerable population selection is used and states: when enrolling participants who are minors, it is necessary to also obtain consent from a legally designated representative and the participant will receive information in a way adapted to their age and mental maturity. (Written informed consent required for all participants.).

Pregnancy Exclusion
1. Females who are pregnant, breastfeeding, or planning to become pregnant during the study period or
Vulnerable Population
The protocol indicates vulnerable population selection is used and states: when enrolling participants who are minors, it is necessary to also obtain consent from a legally designated representative and the participant will receive information in a way adapted to their age and mental maturity. (Written informed consent required for all participants.)

Inclusion criteria

  • {"criterion_text":"- 1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be willing and able to comply with all study requirements. When enrolling participants who are minors, it is necessary to also obtain consent from a legally designated representative and the participant will receive information in a way adapted to their age and mental maturity.\n- 2. Male and females with FSHD confirmed by documented genetic diagnosis as defined below: - FSHD1 - FSHD2\n- 3. 18 to 70 years of age at time of informed consent\n- 4. Able to walk independently at pre-specified walking speed (orthoses or ankle braces are allowed) for at least 10 meters at screening."}

Exclusion criteria

  • {"criterion_text":"- 1. Females who are pregnant, breastfeeding, or planning to become pregnant during the study period or\n- 10. Treatment with an oligonucleotide within 9 months of Screening\n- 11. Blood or plasma donation within 16 weeks of Study Day 1\n- 12. Recent history of or current drug or alcohol abuse in the opinion of the Investigator\n- 13. History of multiple drug allergies or history of allergic reaction to any component of, or excipient in, the Study Drug\n- 14. Presence or history of clinically significant illness, medical condition, or abnormal test result/finding that, in the opinion of the Investigator, could affect a participant’s safety or their ability to comply with study procedures and/or complete the study visit schedule. This may include, but is not limited to, a history of cardiovascular or central nervous system disease, neuromuscular diseases other than FSHD (e.g., myopathy, neuropathy, neuromuscular junction disorders), a cardiopulmonary condition, or a clinically significant mental disorder\n- 2. Males or females not willing to comply with the contraceptive requirements\n- 3. Screening laboratory results or any other clinically significant abnormalities in screening laboratory values that would render a participant unsuitable for inclusion.\n- 4. BP > 140/90 mmHg at Screening\n- 5. Anticipated survival less than 2 years\n- 6. Evidence of current or chronic infection with hepatitis C, hepatitis B, or HIV (including chronic infection requiring ongoing treatment to maintain viral suppression)\n- 7. Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to Study Day 1 or ongoing symptoms related to recent infection causing impairment to ADL in the opinion of the Investigator\n- 8. Malignancy within 5 years, except for basal or squamous cell carcinoma, melanoma in situ of the skin, carcinoma in situ of the cervix, or other malignancies within 5 years that have been treated with curative intent and which are not expected to recur\n- 9. Treatment with another investigational drug or biological agent within 1 month of Screening or 5 half-lives of the drug, whichever is longer; or participation or plan to participate in another interventional study with an investigational drug or device or other types of interventional studies (including those studying behavioral modification and/or physical therapy) while on study"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from Baseline to Week 78 in 10MWRT velocity (m/sec)","definition_or_measurement_approach":"Change from baseline to Week 78 measured as 10MWRT (10-Meter Walk/Run Test) velocity in meters/second."}

Secondary endpoints

  • {"endpoint_text":"- 1.1 Key Secondary Endpoints • Change from Baseline to Week 78 in: o Timed-Up-and-Go (TUG) velocity o NeuroQoL Upper Extremity Function o Quantitative Muscle Testing (QMT) total composite score (PPN)","definition_or_measurement_approach":"Change from baseline to Week 78 measured by: Timed-Up-and-Go (TUG) velocity; NeuroQoL Upper Extremity Function instrument; Quantitative Muscle Testing (QMT) total composite score (percentage of predicted normal, PPN)."}
  • {"endpoint_text":"- 1.2 Other Secondary Endpoints • Change from Baseline over time in: o Patient-reported Outcomes Measurement Information System instruments (PROMIS) (Physical Function) o PROMIS Fatigue o Worst Pain Numerical Rating Scale (NRS) o Patient Global Impression of Severity (PGI-S)/Patient Global Impression of Change (PGI-C) o Quality of Life in Neurological Disorders (NeuroQoL) Sleep Disturbance o DUX4-regulated plasma KHDC1L o Serum CK","definition_or_measurement_approach":"Longitudinal change from baseline in PROMIS Physical Function, PROMIS Fatigue, Worst Pain NRS, PGI-S/PGI-C, NeuroQoL Sleep Disturbance, DUX4-regulated plasma KHDC1L, and serum creatine kinase (CK) measured by the respective validated instruments and laboratory assays over study visits."}

Recruitment

Planned Sample Size
120
Recruitment Window Months
30
Consent Approach
Written informed consent (signed and dated) is required. The protocol specifies that when enrolling minors a legally designated representative must provide consent and the minor participant will receive information adapted to their age and mental maturity. Subject information and informed consent forms are provided (country-specific ICFs listed in documents).

Geography

Total Number Of Sites
20
Total Number Of Participants
80

Italy

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
07-04-2026
Processing Time Days
183
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Neurology
Principal Investigator Name
Mauro Monforte
Principal Investigator Email
mauro.monforte@policlinicogemelli.it
Contact Person Name
Mauro Monforte
Site Name
Azienda Ospedaliero-Universitaria Sant Andre
Department Name
UOC Neurologia
Principal Investigator Name
Matteo Garibaldi
Principal Investigator Email
matteo.garibaldi@uniroma1.it
Contact Person Name
Matteo Garibaldi
Contact Person Email
matteo.garibaldi@uniroma1.it
Site Name
Centro Clinico Nemo
Department Name
Centro Clinico NeMO di Milano
Principal Investigator Name
Valeria Sansone
Principal Investigator Email
valeria.sansone@centrocliniconemo.it
Contact Person Name
Valeria Sansone
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
Experimental and Clinical Medicine, University of Pisa
Principal Investigator Name
Giulia Ricci
Principal Investigator Email
giuli.ricci@med.unipi.it
Contact Person Name
Giulia Ricci
Contact Person Email
giuli.ricci@med.unipi.it

France

Earliest CTIS Part Ii Submission Date
17-09-2025
Latest Decision Or Authorization Date
26-03-2026
Processing Time Days
190
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Centre Hospitalier Universitaire De Nice
Department Name
Neurology Peripheral Nervous System and Muscle
Principal Investigator Name
Sabrina SACCONI
Principal Investigator Email
sacconi.s@chu-nice.fr
Contact Person Name
Sabrina SACCONI
Contact Person Email
sacconi.s@chu-nice.fr
Site Name
Assistance Publique Hopitaux De Paris
Department Name
Neuromyology
Principal Investigator Name
Guillaume BASSEZ
Principal Investigator Email
guillaume.bassez@aphp.fr
Contact Person Name
Guillaume BASSEZ
Contact Person Email
guillaume.bassez@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Centre de Reference des Maladies Neuromusculaires rares et de la SLA
Principal Investigator Name
Shahram ATTARIAN
Principal Investigator Email
shahram.attarian@ap-hm.fr
Contact Person Name
Shahram ATTARIAN
Contact Person Email
shahram.attarian@ap-hm.fr
Site Name
Centre Hospitalier Universitaire De Montpellier
Department Name
Service Explorations Neurologiques et centre de reference SLA
Principal Investigator Name
Florence Esselin
Principal Investigator Email
f-esselin@chu-montpellier.fr
Contact Person Name
Florence Esselin
Contact Person Email
f-esselin@chu-montpellier.fr

Spain

Earliest CTIS Part Ii Submission Date
07-10-2025
Latest Decision Or Authorization Date
24-03-2026
Processing Time Days
168
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Hospital Universitari Vall D Hebron
Department Name
Neurology
Principal Investigator Name
Raul Juntas Morales
Principal Investigator Email
raul.juntas@vallhebron.cat
Contact Person Name
Raul Juntas Morales
Contact Person Email
raul.juntas@vallhebron.cat
Site Name
Hospital Universitario Donostia
Department Name
Neurology
Principal Investigator Name
Adolfo Jose Lopez de Munain Arregui
Contact Person Name
Adolfo Jose Lopez de Munain Arregui
Site Name
Bellvitge University Hospital
Department Name
Neurology
Principal Investigator Name
Velina Nedkova Hristova
Principal Investigator Email
vnedkova@bellvitgehospital.cat
Contact Person Name
Velina Nedkova Hristova
Contact Person Email
vnedkova@bellvitgehospital.cat
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Neurology
Principal Investigator Name
Nuria Muelas Gómez
Principal Investigator Email
muelas_nur@gva.es
Contact Person Name
Nuria Muelas Gómez
Contact Person Email
muelas_nur@gva.es

Netherlands

Earliest CTIS Part Ii Submission Date
07-10-2025
Latest Decision Or Authorization Date
24-03-2026
Processing Time Days
168
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Radboud universitair medisch centrum Stichting
Department Name
Neurology
Principal Investigator Name
Nicol Voermans
Principal Investigator Email
nicol.voermans@radboudumc.nl
Contact Person Name
Nicol Voermans
Contact Person Email
nicol.voermans@radboudumc.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Neurology
Principal Investigator Name
Umesh Arvind Badrising
Principal Investigator Email
u.a.badrising@lumc.nl
Contact Person Name
Umesh Arvind Badrising
Contact Person Email
u.a.badrising@lumc.nl

Denmark

Earliest CTIS Part Ii Submission Date
30-09-2025
Latest Decision Or Authorization Date
24-03-2026
Processing Time Days
175
Number Of Sites
2
Number Of Participants
10

Sites

Site Name
Copenhagen University Hospital
Department Name
Neuromuscular Center
Principal Investigator Name
John Vissing
Principal Investigator Email
john.vissing@regionh.dk
Contact Person Name
John Vissing
Contact Person Email
john.vissing@regionh.dk
Site Name
Aarhus Universitethospital
Department Name
Neurological department
Principal Investigator Name
Henning Andersen
Principal Investigator Email
hennande@rm.dk
Contact Person Name
Henning Andersen
Contact Person Email
hennande@rm.dk

Germany

Earliest CTIS Part Ii Submission Date
06-10-2025
Latest Decision Or Authorization Date
25-03-2026
Processing Time Days
170
Number Of Sites
4
Number Of Participants
15

Sites

Site Name
Universitaetsklinikum Bonn AöR
Department Name
Department of Neuromuscular Diseases
Principal Investigator Name
Jens Reimann
Principal Investigator Email
jens.reimann@ukbonn.de
Contact Person Name
Jens Reimann
Contact Person Email
jens.reimann@ukbonn.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Department of Neurology
Principal Investigator Name
Jana Zschüntzsch
Principal Investigator Email
j.zschuentzsch@med.uni-goettingen.de
Contact Person Name
Jana Zschüntzsch
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Department of Neurology
Principal Investigator Name
Angela Rosenbohm
Principal Investigator Email
angela.rosenbohm@uni-ulm.de
Contact Person Name
Angela Rosenbohm
Contact Person Email
angela.rosenbohm@uni-ulm.de
Site Name
LMU Klinikum Muenchen AöR
Department Name
Department of Neurology
Principal Investigator Name
Benedikt Schoser
Principal Investigator Email
benedikt.schoser@med.uni-muenchen.de
Contact Person Name
Benedikt Schoser

Sponsor

Primary sponsor

Full Name
Avidity Biosciences Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
Medpace Finland Oy
Responsibilities
Medical Monitoring, IDMC, QA, Site Contract and Budget Negotiation/Execution, Study Vendor Management
Name
PPD Development LP
Name
ProPharma Group GmbH
Name
Gray Consulting Inc.
Responsibilities
Patient Travel and Reimbursement Support

Third parties

  • {"country":"United Kingdom","full_name":"ATOM International Limited","duties_or_roles":"Clinical Evaluator Oversight and Training/Activities for Measures of Function and Strength Assessments","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"University Of Iowa Hospitals And Clinics","duties_or_roles":"","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Patient Travel and Reimbursement Support","organisation_type":"Pharmaceutical company"}
  • {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Medical Monitoring, IDMC, QA, Site Contract and Budget Negotiation/Execution, Study Vendor Management","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Packaging Coordinators LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Atreo Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"ProPharma Group GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
AOC 1020
Active Substance
Humanised IgG1 monoclonal antibody against TfR1 conjugated to double stranded siRNA oligonucleotide against DUX4 mRNA via a non-cleavable linker
Modality
Monoclonal antibody | Oligonucleotide
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS
Orphan Designation
Yes
Maximum Dose
Max daily dose 2 mg/kg; max total dose 26 mg
Investigational Product Name
0.9% Saline for IV administration
Modality
Other
Routes Of Administration
INTRAVENOUS
Route
INTRAVENOUS

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