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Humanised Igg1 Monoclonal Antibody Against Tfr1 Conjugated To Double Stranded Sirna Oligonucleotide Against Dmpk Via A Non-Cleavable Linker

A groundbreaking Phase 3 clinical trial is underway to assess the efficacy and safety of AOC 1001, a promising new drug for treating Myotonic Dystrophy Type 1 (DM1). This study aims to evaluate how AOC 1001, administered intravenously, affects hand function, mobility, muscle strength, and overall quality of life in patients with DM1. The trial represents a significant step forward in developing targeted therapies for this rare genetic disorder.

Table of Contents

What is AOC 1001?

AOC 1001 is an innovative medication being developed to treat Myotonic Dystrophy Type 1 (DM1). It is classified as a humanised IgG1 monoclonal antibody that targets a specific protein called TFR1. This antibody is connected to a special type of genetic material (siRNA) that targets a gene called DMPK, which is involved in DM1.[1]

In simpler terms, AOC 1001 is designed to deliver a targeted treatment directly to the cells affected by DM1. It combines two important components:

  1. An antibody that helps the drug reach the right cells
  2. A genetic component that aims to reduce the harmful effects of the faulty gene in DM1

Target Condition: Myotonic Dystrophy Type 1

Myotonic Dystrophy Type 1 (DM1) is a genetic disorder that affects muscles and many other body systems. It causes muscle weakness, difficulty relaxing muscles (myotonia), and can impact the heart, brain, and other organs. DM1 is caused by a specific genetic change in the DMPK gene.[1]

Clinical Trial Overview

A Phase 3 clinical trial is currently underway to evaluate the effectiveness and safety of AOC 1001 for treating DM1. This study is:

  • Randomized: Participants are randomly assigned to either receive AOC 1001 or a placebo
  • Double-blind: Neither the participants nor the researchers know who is receiving the actual drug
  • Placebo-controlled: Some participants will receive a placebo (an inactive substance) for comparison
  • Global: The study is being conducted in multiple countries

This trial represents an advanced stage of research, aiming to confirm the drug’s benefits and safety in a larger group of patients.[1]

Eligibility Criteria

To participate in this study, individuals must meet certain criteria. Some key inclusion criteria are:

  • Age: 16 to 65 years old (18-65 in Denmark and Germany)
  • Confirmed diagnosis of DM1, both clinically and genetically (with at least 100 CTG repeats in the affected gene)
  • Ability to walk independently for at least 10 meters (use of ankle braces or orthoses is allowed)

Some exclusion criteria include:

  • Pregnancy or breastfeeding
  • Uncontrolled diabetes
  • Recent history of heart failure
  • Body Mass Index (BMI) greater than 35 kg/m²
  • Recent use of certain medications or participation in other clinical trials

These criteria help ensure the safety of participants and the reliability of the study results.[1]

Study Objectives and Endpoints

The main goal of this study is to evaluate how well AOC 1001 improves hand function in people with DM1. Researchers will measure this by looking at the change in video Hand Opening Time (vHOT) from the start of the study to week 30.[1]

Other important aspects being studied include:

  • Changes in muscle strength and function
  • Improvements in mobility
  • Patient-reported outcomes (how patients feel the treatment is affecting their daily lives)

These will be measured using various tests and questionnaires, such as:

  • Hand grip strength: Measures how strongly a person can grip
  • QMT (Quantitative Muscle Testing): Assesses strength in different muscle groups
  • DM1-ActivC: A questionnaire about daily activities specific to DM1 patients
  • 10MWRT (10-Meter Walk/Run Test): Measures walking speed
  • PGI-S and PGI-C: Patient-reported impressions of symptom severity and change
  • EQ-5D-5L: A general health-related quality of life questionnaire

These measurements will be taken at various points during the study, including at 30 weeks and 54 weeks after starting treatment.[1]

Drug Administration

AOC 1001 is given as an intravenous infusion, which means it’s delivered directly into the bloodstream through a vein. The maximum daily dose is 4 mg/kg (milligrams per kilogram of body weight), with a total maximum dose of 28 mg/kg over the course of treatment. The treatment period lasts up to 54 weeks.[1]

Potential Benefits and Orphan Drug Status

While the full benefits of AOC 1001 are still being studied, its development as a targeted therapy for DM1 offers hope for patients with this rare disease. The European Union has granted AOC 1001 orphan drug designation (EU/3/21/2485), which is given to medicines intended for the treatment of rare diseases. This status can help accelerate the development and approval process for drugs that address significant unmet medical needs.[1]

It’s important to note that as this is an ongoing clinical trial, the effectiveness and safety of AOC 1001 are still being evaluated. Patients interested in this treatment should discuss it with their healthcare providers and consider the potential risks and benefits of participating in clinical research.

Aspect Details
Study Type Phase 3, Randomized, Double-Blind, Placebo-Controlled, Global Study
Drug Name AOC 1001
Target Condition Myotonic Dystrophy Type 1 (DM1)
Primary Endpoint Change in video Hand Opening Time (vHOT) from baseline to Week 30
Key Secondary Endpoints Changes in hand grip strength, muscle strength (QMT scores), mobility (10MWRT), and quality of life measures (DM1-ActivC, EQ-5D-5L)
Dosing Intravenous infusion, max 4 mg/kg daily, 28 mg/kg total over 54 weeks
Key Inclusion Criteria Age 16-65, DM1 diagnosis with CTG repeat ≥100, ability to walk 10 meters independently
Key Exclusion Criteria Pregnancy, uncontrolled diabetes, recent heart failure, BMI >35 kg/m²

FAQ

  • What is AOC 1001? AOC 1001 is a novel drug consisting of a humanized IgG1 monoclonal antibody against TfR1 conjugated to a double-stranded siRNA oligonucleotide targeting DMPK via a non-cleavable linker. It is being developed as a potential treatment for Myotonic Dystrophy Type 1.
  • What is the main goal of this clinical trial? The main objective of this trial is to evaluate the efficacy of AOC 1001 on hand function in patients with Myotonic Dystrophy Type 1. This will be measured by assessing the change in video Hand Opening Time (vHOT) from baseline to Week 30 of treatment.
  • Who can participate in this clinical trial? Participants must be between 16 and 65 years old (18-65 in Denmark and Germany), have a clinical and genetic diagnosis of DM1 with a CTG repeat length ≥ 100, and be able to walk independently for at least 10 meters. There are additional inclusion and exclusion criteria that participants must meet.
  • How is AOC 1001 administered in this trial? AOC 1001 is administered intravenously as a solution for infusion. The maximum daily dose is 4 mg/kg, with a maximum total dose of 28 mg/kg over a treatment period of up to 54 weeks.
  • What outcomes will be measured in this trial? The trial will measure changes in hand function, muscle strength, mobility, and patient-reported outcomes. Specific measures include video Hand Opening Time, hand grip strength, quantitative muscle testing scores, 10-meter walk/run test, and quality of life assessments using standardized questionnaires.

Ongoing Clinical Trials on Humanised Igg1 Monoclonal Antibody Against Tfr1 Conjugated To Double Stranded Sirna Oligonucleotide Against Dmpk Via A Non-Cleavable Linker

  • Study of intravenous AOC 1001 to evaluate long-term safety and effectiveness in patients with myotonic dystrophy type 1

    Recruiting

    3 1 1
    Investigated drugs:
    Denmark France Germany Italy The Netherlands Spain

  • Study on AOC 1001 for Treating Myotonic Dystrophy Type 1 in Patients

    Not recruiting

    3 1
    Investigated drugs:
    Denmark France Germany Ireland Italy The Netherlands +1

Glossary

  • Myotonic Dystrophy Type 1 (DM1): A genetic disorder characterized by progressive muscle weakness, myotonia (difficulty relaxing muscles), and involvement of other organs. It is caused by an expansion of CTG repeats in the DMPK gene.
  • CTG repeat: A sequence of DNA bases (cytosine-thymine-guanine) that is repeated multiple times in the DMPK gene. In DM1, this repeat is abnormally expanded, causing the disease.
  • Monoclonal Antibody: A type of protein made in the laboratory that can bind to specific targets in the body. In this case, it's designed to target TfR1 (Transferrin Receptor 1).
  • siRNA: Small interfering RNA, a type of molecule that can interfere with the expression of specific genes. In AOC 1001, it's designed to target the DMPK gene.
  • TfR1: Transferrin Receptor 1, a protein involved in iron uptake by cells. It's used as a target in AOC 1001 to help deliver the drug to specific cells.
  • DMPK: Dystrophia Myotonica Protein Kinase, the gene affected in Myotonic Dystrophy Type 1. AOC 1001 is designed to target this gene.
  • vHOT: Video Hand Opening Time, a measure used to assess hand function in patients with DM1.
  • QMT: Quantitative Muscle Testing, a method used to measure muscle strength objectively.
  • 10MWRT: 10-Meter Walk/Run Test, a measure of mobility and walking speed.
  • DM1-ActivC: A patient-reported outcome measure specifically designed for DM1 patients to assess their ability to perform daily activities.

References

  1. http://clinicaltrials.eu/trial/study-on-aoc-1001-for-treating-myotonic-dystrophy-type-1-in-patients/