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Antisense - ATL1102
A Multicentre, Randomised, Double-blind, Placebo-controlled and Open Label Extension Study to Assess the Efficacy, Safety, and Pharmacokinetic Profile of ATL1102 in Non-ambulatory Participants With Duchenne Muscular Dystrophy
Hub Summary
This Phase IIb study is a two part, multicenter study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of ATL1102 in non-ambulant boys with Duchenne Muscular Dystrophy aged 10 to 17 years old. The study includes a randomised, double-blind, placebo-controlled treatment period (Part A), followed by an open labelled treatment period (Part B).
Study Number: NCT05938023
Description by Antisense Therapeutics Limited
This Phase IIb study is a two part, multicenter study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of ATL1102 and will enroll 45 non-ambulant boys with Duchenne Muscular Dystrophy (DMD) aged 10 to <18 years old.
During the 24 week randomised, double-blind, placebo-controlled treatment period (Part A) participants will be enrolled and randomised to receive either ATL1102 25mg, ATL1102 50mg or matched placebo in a 1:1:1 ratio given as a weekly subcutaneous injection.
Participants will then continue to the 24 week Open Labelled Treatment Period (Part B) and continue to receive ATL1102 25mg or ATL1102 50mg for a further 24 weeks. Participants on placebo in Part A will transition to ATL1102.
The study will consist of a 4 week screening period, 24 week randomised, double-blind, placebo-controlled treatment period (Part A), 24 week open label treatment period (Part B) and 16 week follow up period.
Primary Outcome Measures
- Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 25 (blinded treatment period). [ Time Frame: 25 weeks ]
The PUL is an assessment used to evaluate the upper limb strength for individuals with DMD where a higher score indicates a better outcome with a minimum of 0 and a maximum score of 42
- Change in the Performance of Upper Limb (PUL) 2.0 score from Week 25 to Week 49 (open label treatment period). [ Time Frame: 49 weeks ]
The PUL is an assessment used to evaluate the upper limb strength for individuals with DMD where a higher score indicates a better outcome with a minimum of 0 and a maximum score of 42
- Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 49 (combined treatment period). [ Time Frame: 49 weeks ]
The PUL is an assessment used to evaluate the upper limb strength for individuals with DMD where a higher score indicates a better outcome with a minimum of 0 and a maximum score of 42
- Safety measured by the incidence and frequency of adverse events, serious adverse events and suspected unexpected adverse events from baseline to Week 65 [ Time Frame: 65 weeks ]
An Adverse Event is any untoward medical occurrence in a participant and does not necessarily have to have a causal relationship with the intervention.
Secondary Outcome Measures
- Change in the grip strength of the hand from baseline to Week 25 using a handheld dynamometer tool (MyoGrip) (blinded treatment period). [ Time Frame: 25 weeks ]
The handheld dynamometer tool (MyoGrip) use strain gauge technology to measure the hand strength in Kilograms exerted by the participants with higher recordings indicating greater hand strength.
- Change in the pinch strength of the fingers from baseline to Week 25 using handheld dynamometer tool (MyoPinch) (blinded treatment period). [ Time Frame: 25 weeks ]
The handheld dynamometer tool (MyoPinch) use strain gauge technology to measure the pinch strength of the fingers in Kilograms exerted by the participants with higher recordings indicating greater hand strength.
- Change in the respiratory function assessed by Forced Vital Capacity (FVC) from baseline to Week 25 (blinded treatment period). [ Time Frame: 25 weeks ]
The percent predicted for Forced Vital Capacity (FVC%p) will be calculated at multiple timepoints after respiratory function is assessed using spirometry tests
- Change in the respiratory function assessed by peak expiratory flow (PEF) from baseline to Week 25 (blinded treatment period). [ Time Frame: 25 weeks ]
The percent predicted for peak expiratory flow (PEF%p) will be calculated at multiple timepoints after respiratory function is assessed using spirometry tests
- Change in the Paediatric Quality of Life (PedsQL™) questionnaire Duchenne Muscular Dystrophy (DMD) Module from baseline to Week 25 (blinded treatment period). [ Time Frame: 25 weeks ]
Health related quality of life is assessed by percentage of change in the score collected in the Paediatric Quality of Life (PedsQL™) Duchenne Muscular Dystrophy (DMD) Module for participants and parents at multiple timepoints. A higher score indicates a better health related quality of life with a minimum of 0 and a maximum score of 100.
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Other Secondary Outcome Measures can be found on Clinicaltrial.gov
Other Outcome Measures
Changes in lymphocyte populations to assess pharmacodynamic effects of ATL1102 from baseline to Week 57 [ Time Frame: 57 weeks ]
Lymphocyte population (cells/L) including cells expressing CD49d will be evaluated at multiple timepoints during the study utilizing chip cytometry.
Can I take part?
Inclusion Criteria
- Has a clinical diagnosis of DMD confirmed by validated genetic testing
- Is considered to be non-ambulatory, defined as unable to walk 10 meters without assistance or help at Screening.
- Male aged 10 to less than 18 years, at the time of Screening.
- Body weight of at least 25 kg at Screening.
- If receiving corticosteroid therapy, therapy was initiated at least six months prior to the baseline visit and a stable daily dose for at least 3 months prior to baseline
- Participant has a Performance of Upper Limb Module for DMD 2.0 (PUL 2.0) Entry Item A score ≥2.
- Able to perform spirometry and has sufficient Respiratory function defined as reproducible percent predicted FVC ≥50%.
- Has adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥45% by echocardiogram and if receiving cardiac medication, must be currently on a stable regimen and doses of cardiac therapy (at least 3 months prior to baseline Day 1)
- Participant and their parent/guardian/carer are willing and able to comply with scheduled visits, study medication administration and study procedures.
Exclusion Criteria
- Participation in another clinical trial (non-interventional) or administration of any investigational product or experimental product within 12 weeks or 5 half-lives (whichever is longer) preceding Day 1.
- Exposure to more than 3 investigational products within the 12 months prior to Day 1.
- History of clinically significant bleeding or coagulation abnormalities or clinically significant abnormal coagulation parameters.
- Currently receiving antiplatelet or anticoagulant therapy or has taken medication with an antiplatelet or anticoagulant effect within 4 weeks prior Day 1
- Any evidence of clinically significant structural or functional heart abnormality (cardiomyopathy that is managed by ACEi or beta blockers is acceptable provided the LVEF inclusion criterion is met).
- Known history of or a positive test for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibodies, human immunodeficiency virus (HIV) antibodies at Screening.
- Evidence of renal impairment and/or cystatin C >1.4 mg/L.
- Received a live vaccine (including intranasal influenza vaccine) within 4 weeks prior to Day 1 or planned live vaccination during the study period.
- Asthma (if requiring regular medication), bronchitis/chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, pneumonia or the presence of any non-DMD respiratory illness that affects PEF and FVC or other respiratory measures.
- Requires day-time assisted mechanical or non-invasive ventilation (NIV) (night time NIV is permitted).
- Chronic use (daily intake >14 days), within one month of Day 1, of beta-2 agonists or any use of other bronchodilating medication (e.g., inhaled steroids, sympathomimetics, anticholinergics).
- Used carnitine, creatine, glutamine, oxatomide, idebenone or other forms of coenzyme Q10 or vitamin E or any other nutritional or antioxidant supplements or herbal medicines or anabolic steroids other than standard corticosteroids or puberty testosterone supplementation within 4 weeks of Day 1.
- Has an increased risk for opportunistic infections or systemic medical conditions resulting in significantly compromised immune system function
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Fully recruited
Antisense Therapeutics Limited