Clinical trial NCT05938023: A Study of ATL1102 or Placebo in Participants With Non-ambulatory Duchenne Muscular Dystrophy
Official title: A Multicentre, Randomised, Double-blind, Placebo-controlled and Open Label Extension Study to Assess the Efficacy, Safety, and Pharmacokinetic Profile of of ATL1102 in Non-ambulatory Participants With Duchenne Muscular Dystrophy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: Non-ambulatory
DMD
Lead sponsor: Percheron Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-07-10
Enrollment: 48
Sex: MALE
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, double-blind, placebo controlled treatment periods followed by open labelled treatment period
Primary purpose: TREATMENT

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).

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.

Eligibility 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 1)
* 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

Primary outcomes:
measure: Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 25 (blinded treatment period).
timeFrame: 25 weeks
measure: Change in the Performance of Upper Limb (PUL) 2.0 score from Week 25 to Week 49 (open label treatment period).
timeFrame: 49 weeks
measure: Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 49 (combined treatment period).
timeFrame: 49 weeks
measure: Safety measured by the incidence and frequency of adverse events, serious adverse events and suspected unexpected adverse events from baseline to Week 65
timeFrame: 65 weeks
Secondary outcomes:
measure: Change in the grip strength of the hand from baseline to Week 25 using a handheld dynamometer tool (MyoGrip) (blinded treatment period).
timeFrame: 25 weeks
measure: Change in the pinch strength of the fingers from baseline to Week 25 using handheld dynamometer tool (MyoPinch) (blinded treatment period).
timeFrame: 25 weeks
measure: Change in the respiratory function assessed by Forced Vital Capacity (FVC) from baseline to Week 25 (blinded treatment period).
timeFrame: 25 weeks
measure: Change in the respiratory function assessed by peak expiratory flow (PEF) from baseline to Week 25 (blinded treatment period).
timeFrame: 25 weeks
measure: Change in the Paediatric Quality of Life (PedsQL™) questionnaire Duchenne Muscular Dystrophy (DMD) Module from baseline to Week 25 (blinded treatment period).
timeFrame: 25 weeks
measure: 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).
timeFrame: 25 weeks
measure: Maximum and minimum plasma concentration (Cmax and Cmin) for ATL1102 over multiple timepoints
timeFrame: 65 weeks
measure: Area under the plasma concentration time curve (AUC) for ATL1102 over multiple timepoints
timeFrame: 65 weeks
measure: Time to Cmax and Cmin for ATL1102 over multiple timepoints
timeFrame: 65 weeks
measure: The terminal half life for ATL1102
timeFrame: 65 weeks
measure: Change in the grip strength of the hand from Week 25 to Week 49 using a handheld dynamometer tool (MyoGrip) (open label treatment period).
timeFrame: 49 weeks
measure: Change in the pinch strength of the fingers from Week 25 to Week 49 using handheld dynamometer tool (MyoPinch) (open label treatment period).
timeFrame: 49 weeks
measure: Change in the respiratory function assessed by Forced Vital Capacity (FVC) from Week 25 to Week 49 (open label treatment period).
timeFrame: 49 weeks
measure: Change in the respiratory function assessed by peak expiratory flow (PEF) from Week 25 to Week 49 (open label treatment period).
timeFrame: 49 weeks
measure: Change in the Paediatric Quality of Life (PedsQL) questionnaire Duchenne Muscular Dystrophy (DMD) Module from Week 25 to Week 49 (open label treatment period).
timeFrame: 49 weeks
measure: Change in the grip strength of the hand from baseline to Week 49 using a handheld dynamometer tool (MyoGrip) (combined treatment period).
timeFrame: 49 weeks
measure: Change in the pinch strength of the fingers from Baseline to Week 49 using handheld dynamometer tool (MyoPinch) (combined treatment period).
timeFrame: 49 weeks
measure: Change in the respiratory function assessed by Forced Vital Capacity (FVC) from Baseline to Week 49 (combined treatment period).
timeFrame: 49 weeks
measure: Change in the respiratory function assessed by peak expiratory flow (PEF) from baseline to Week 49 (combined treatment period).
timeFrame: 49 weeks
measure: Change in the Paediatric Quality of Life (PedsQL) questionnaire Duchenne Muscular Dystrophy (DMD) Module from Baseline to Week 49 (combined treatment period).
timeFrame: 49 weeks
Other outcomes:
measure: Changes in lymphocyte populations to assess pharmacodynamic effects of ATL1102 from baseline to Week 57
timeFrame: 57 weeks
Locations:
city: Melbourne
country: Australia
facility: Royal Childrens Hospital
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Westmead
country: Australia
facility: The Children's Hospital at Westmead
city: Sofia
country: Bulgaria
facility: UMHAT Aleksandrovska Neurology clinic
city: Belgrade
country: Serbia
facility: University Children's Hospital
city: Belgrade
country: Serbia
facility: Mother and Child Health Care Institute
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi Universitesi Tip Fakultesi
city: Istanbul
country: Turkey
facility: Yeditepe University Hospital
city: Pendik
country: Turkey
facility: Marmara University Pendik Training and Research Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Leeds
country: United Kingdom
facility: The General Infirmary at Leeds, Leeds Teaching Hospital NHS Trust
city: London
country: United Kingdom
facility: University College London (UCL) - Great Ormond Street Institute of Child Health (ICH)
city: Oswestry
country: United Kingdom
facility: The Robert Jones and Agnes Hunt Orthopaedic Hospital
Study officials:
affiliation: UCL Great Ormond Street Institute of Child Health
name: Thomas Voit
role: PRINCIPAL_INVESTIGATOR
References: