A Study of ATL1102 or Placebo in Participants With Non-ambulatory Duchenne Muscular Dystrophy
Study Details
Study Description
Brief 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 <18 years old. The study includes a randomised, double-blind, placebo-controlled treatment period (Part A), followed by an open labelled treatment period (Part B).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ATL1102 25mg ATL1102 25mg administered subcutaneously once weekly |
Drug: ATL1102 25mg
Dose and scheduled as specified in the Arm description
|
| Experimental: ATL1102 50mg ATL1102 50mg administered subcutaneously once weekly |
Drug: ATL1102 50mg
Dose and scheduled as specified in the Arm description
|
| Placebo Comparator: Placebo Placebo is administered subcutaneously once weekly |
Drug: Placebo
Dose and scheduled as specified in the Arm description
|
Outcome Measures
Primary Outcome Measures
- Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 25 (blinded treatment period). [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). [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). [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 [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). [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). [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). [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). [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). [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.
- Safety measured by the incidence and frequency of adverse events, serious adverse events and suspected unexpected adverse events from baseline to Week 25 (blinded treatment period). [25 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.
- Maximum and minimum plasma concentration (Cmax and Cmin) for ATL1102 over multiple timepoints [65 weeks]
Pharmacokinetic evaluation to evaluate dose response
- Area under the plasma concentration time curve (AUC) for ATL1102 over multiple timepoints [65 weeks]
Pharmacokinetic evaluation to evaluate dose concentration over time
- Time to Cmax and Cmin for ATL1102 over multiple timepoints [65 weeks]
Pharmacokinetic evaluation to evaluate concentration of ATL1102
- The terminal half life for ATL1102 [65 weeks]
Pharmacokinetic evaluation to evaluate the time for the ATL1102 concentration to reduce by half
- Change in the grip strength of the hand from Week 25 to Week 49 using a handheld dynamometer tool (MyoGrip) (open label treatment period). [49 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 Week 25 to Week 49 using handheld dynamometer tool (MyoPinch) (open label treatment period). [49 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 Week 25 to Week 49 (open label treatment period). [49 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 Week 25 to Week 49 (open label treatment period). [49 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 Week 25 to Week 49 (open label treatment period). [49 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.
- Change in the grip strength of the hand from baseline to Week 49 using a handheld dynamometer tool (MyoGrip) (combined treatment period). [49 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 49 using handheld dynamometer tool (MyoPinch) (combined treatment period). [49 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 49 (combined treatment period). [49 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 49 (combined treatment period). [49 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 49 (combined treatment period). [49 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.
Other Outcome Measures
- Changes in lymphocyte populations to assess pharmacodynamic effects of ATL1102 from baseline to Week 57 [57 weeks]
Lymphocyte population (cells/L) including cells expressing CD49d will be evaluated at multiple timepoints during the study utilizing chip cytometry.
Eligibility Criteria
Criteria
Key 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
- Participant and their parent/guardian/carer are willing and able to comply with scheduled visits, study medication administration and study procedures.
Key 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital at Westmead | Westmead | New South Wales | Australia | 2145 |
| 2 | Queensland Children's Hospital | South Brisbane | Queensland | Australia | 4101 |
| 3 | Royal Childrens Hospital | Melbourne | Victoria | Australia | 3052 |
| 4 | UMHAT Aleksandrovska Neurology clinic | Sofia | Bulgaria | 1432 | |
| 5 | Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi | Pendik | Istanbul | Turkey | 34899 |
| 6 | Eskisehir Osmangazi Universitesi Tip Fakultesi | Eskisehir | Turkey | 26040 | |
| 7 | Yeditepe Üniversitesi Hastanesi [Yeditepe University Hospital] | Istanbul | Turkey | ||
| 8 | Birmingham Heartlands Hospital | Birmingham | England | United Kingdom | B9 5SS |
| 9 | The General Infirmary at Leeds, Leeds Teaching Hospital NHS Trust | Leeds | England | United Kingdom | LS2 9NS |
| 10 | University College London (UCL) - Great Ormond Street Institute of Child Health (ICH) | London | England | United Kingdom | WC1N 3JH |
| 11 | Manchester Royal Infirmary | Manchester | England | United Kingdom | M13 9WL |
| 12 | The Robert Jones and Agnes Hunt Orthopaedic Hospital | Gobowen | Shropshire | United Kingdom | SY10 7AG |
Sponsors and Collaborators
- Antisense Therapeutics Limited
Investigators
- Principal Investigator: Thomas Voit, UCL Great Ormond Street Institute of Child Health
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 1102-DMD-Pre-CT03