Clinical trial • Phase III • Musculoskeletal

Humanised IgG1 monoclonal antibody against TFR1 conjugated to double stranded siRNA oligonucleotide against DMPK via a non-cleavable linker for Myotonic dystrophy type 1

Phase III trial of Humanised IgG1 monoclonal antibody against TFR1 conjugated to double stranded siRNA oligonucleotide against DMPK via a non-cleavable li…

Overview

Trial Therapeutic Area
Musculoskeletal
Trial Disease
Myotonic dystrophy type 1
Trial Stage
Phase III
Drug Modality
Monoclonal antibody|Oligonucleotide
Paediatric Trial
Yes
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
17-05-2024
First CTIS Authorization Date
08-08-2024

Trial design

Randomised, placebo: 0.9% saline for iv administration (placebo comparator). no dose/schedule specified in the available dataset.-controlled Phase III trial in France, Germany, Denmark and others.

Randomised
Yes
Comparator
Placebo: 0.9% Saline for IV administration (placebo comparator). No dose/schedule specified in the available dataset.
Target Sample Size
111
Trial Duration For Participant
378

Eligibility

Recruits 111 paediatric patients.

Pregnancy Exclusion
1. Breastfeeding, pregnancy, or intent to become pregnant during the study.
Vulnerable Population
Vulnerable population selected. Minors are included in some countries (age 16–17 allowed per inclusion criteria; Denmark and Germany restrict to 18–65). Assent and parental/guardian consent documents are provided (documents listed include L1_SIS and ICF_Assent, L1_SIS and ICF_Parental, L1_SIS and ICF_Parent_Guardian), indicating assent for minors and parental/guardian consent handling as per the provided subject information and consent forms.

Inclusion criteria

  • {"criterion_text":"- 1. Age: 16 to 65. Age: 18-65 (Denmark, Germany)\n- 2. Clinical and genetic diagnosis (CTG repeat length ≥ 100) of DM1.\n- 3. Ability to walk independently (orthoses and ankle braces allowed) for at least 10 meters at screening."}

Exclusion criteria

  • {"criterion_text":"- 1. Breastfeeding, pregnancy, or intent to become pregnant during the study.\n- 2. Unwilling or unable to comply with contraceptive requirements.\n- 3. Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study.\n- 4. Diabetes that is not adequately controlled.\n- 5. History of decompensated heart failure within 3 months of screening. Participants with preexisting pacemaker/ICD are not excluded.\n- 6. Body Mass Index > 35 kg/m2 at Screening.\n- 7. Recently treated with an investigational drug or biological agent.\n- 8. Treatment with anti-myotonic medication within 5 half-lives or 14 days of baseline, whichever is longer, prior to baseline.\n- 9. Note: Additional protocol defined inclusion and exclusion criteria apply."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline to Week 54 in video Hand Opening Time (vHOT).","definition_or_measurement_approach":"Measured as change from baseline to Week 54 in video Hand Opening Time (vHOT)."}

Secondary endpoints

  • {"endpoint_text":"- 1. Change from baseline to Week 54 in: • Hand grip strength. • QMT total composite score. • DM1-ActivC. • 10MWRT","definition_or_measurement_approach":"Measured as change from baseline to Week 54 in the listed measures (hand grip strength, QMT total composite score, DM1-ActivC, 10MWRT)."}
  • {"endpoint_text":"- 2. Change from baseline to Week 54 in: • QMT upper extremity composite score. • QMT lower extremity composite score. • QMT individual muscle group scores. • PGI-S. • EQ-5D-5L. PGI-C at Week 54","definition_or_measurement_approach":"Measured as change from baseline to Week 54 in the listed QMT composite and individual scores, PGI-S, EQ-5D-5L and PGI-C at Week 54."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
111
Recruitment Window Months
24
Consent Approach
Informed consent documented via L1_SIS and ICF_Adults forms for adult participants. Assent is provided using L1_SIS and ICF_Assent forms for minors; parental/guardian consent handled via L1_SIS and ICF_Parental / L1_SIS and ICF_Parent_Guardian forms. Country-specific age inclusion differences noted (general age 16–65; Denmark and Germany 18–65), so local age-specific consent/assent procedures apply as per the provided subject information and consent documents.

Methods

  • Country-specific recruitment arrangements and materials (K1 recruitment arrangements documents per country).
  • Printed and participant-facing materials: brochure, participant handbook, participant journey (K2 recruitment material files).
  • Site-based recruitment at participating neurology/neuromuscular clinics and hospitals listed in Part II site lists.
  • Patient travel and reimbursement support (service provided by Gray Consulting Inc. / Clincierge) to facilitate participation.
  • Use of digital tools and ePRO (ePRO screenshots, ePRO reminders, TrialPACE/ePRO materials) to support participant procedures and communications.
  • Video-based assessment support (video Hand Opening Time) provided by Aparito (documented duty: Video hand opening time assessment).

Geography

Total Number Of Sites
11
Total Number Of Participants
39

France

Earliest CTIS Part Ii Submission Date
01-08-2024
Latest Decision Or Authorization Date
08-04-2026
Processing Time Days
616
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Hopitaux Universitaires Pitie Salpetriere
Department Name
Neuromyologie
Contact Person Name
Guillaume Bassez
Contact Person Email
guillaume.bassez@aphp.fr
Site Name
Centre Hospitalier Regional De Marseille
Department Name
Maladies neuromusculaires
Contact Person Name
Shahram Attarian
Contact Person Email
Shahram.ATTARIAN@ap-hm.fr

Germany

Earliest CTIS Part Ii Submission Date
09-08-2024
Latest Decision Or Authorization Date
09-04-2026
Processing Time Days
608
Number Of Sites
1
Number Of Participants
6

Sites

Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Department of Neurology
Contact Person Name
Stephan Wenninger

Denmark

Earliest CTIS Part Ii Submission Date
06-08-2024
Latest Decision Or Authorization Date
08-04-2026
Processing Time Days
610
Number Of Sites
2
Number Of Participants
6

Sites

Site Name
Copenhagen University Hospital
Department Name
Neuromuskulaer klinik
Contact Person Name
Nicolai Preisler
Site Name
Aarhus Universitetshospital
Department Name
Neurological department
Contact Person Name
Henning Andersen
Contact Person Email
hennande@rm.dk

Spain

Earliest CTIS Part Ii Submission Date
10-07-2024
Latest Decision Or Authorization Date
13-04-2026
Processing Time Days
642
Number Of Sites
1
Number Of Participants
2

Sites

Site Name
Hospital Universitario Donostia
Department Name
Neurology
Contact Person Name
Adolfo Jose Lopez de Munain Arregui

Ireland

Earliest CTIS Part Ii Submission Date
18-07-2024
Latest Decision Or Authorization Date
23-04-2025
Processing Time Days
279
Number Of Sites
1
Number Of Participants
3

Sites

Site Name
Beaumont Hospital
Department Name
Neurology
Contact Person Name
Stela Lefter
Contact Person Email
stelalefter2@beaumont.ie

Netherlands

Earliest CTIS Part Ii Submission Date
12-08-2024
Latest Decision Or Authorization Date
08-04-2026
Processing Time Days
604
Number Of Sites
2
Number Of Participants
9

Sites

Site Name
Stichting Radboud universitair medisch centrum
Department Name
Neurology
Contact Person Name
Karlien Mul
Contact Person Email
karlien.mul@radboudumc.nl
Site Name
Academisch Ziekenhuis Maastricht
Department Name
Neurology
Contact Person Name
Catharina Faber
Contact Person Email
c.faber@mumc.nl

Italy

Earliest CTIS Part Ii Submission Date
03-06-2024
Latest Decision Or Authorization Date
14-04-2026
Processing Time Days
680
Number Of Sites
2
Number Of Participants
7

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
NeuroScience, Sensory Organs and Chest
Contact Person Name
Gabriella Silvestri
Site Name
Centro Clinico Nemo
Department Name
Centro Clinico NeMO di Milano
Contact Person Name
Valeria Sansone

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
Sponsor duties codes: 1,10,11,12,2,3,4,5,6,7
Name
ProPharma Group GmbH
Responsibilities
Sponsor duties code: 8
Name
Medidata Solutions Inc.
Responsibilities
Sponsor duties code: 7

Third parties

  • {"country":"United States","full_name":"Packaging Coordinators LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"ProPharma Group GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Aparito Limited","duties_or_roles":"Video hand opening time assessment","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Gray Consulting Inc.","duties_or_roles":"Patient travel and reimbursement support","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Trinds LLC","duties_or_roles":"Clinical evaluator oversight & Motor function test training/Activities","organisation_type":"Pharmaceutical company"}
  • {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Atreo Inc.","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}

Investigational products

Investigational Product Name
AOC 1001
Active Substance
Humanised IgG1 monoclonal antibody against TFR1 conjugated to double stranded siRNA oligonucleotide against DMPK via a non-cleavable linker
Modality
Monoclonal antibody|Oligonucleotide
Routes Of Administration
Intravenous
Route
Intravenous
Orphan Designation
Yes
Maximum Dose
Max daily: 4 mg/kg; Max total: 28 mg/kg
Investigational Product Name
0.9% Saline for IV administration
Modality
Other
Routes Of Administration
Intravenous
Route
Intravenous

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