A Study of ATL1102 or Placebo in Participants With Non-ambulatory Duchenne Muscular Dystrophy

• ClinicalTrials.gov Identifier: NCT05938023
• Recruitment Status: Recruiting
• First Posted: July 10, 2023
• Last Update Posted: March 18, 2024
• Sponsor: Percheron Therapeutics
• Information provided by (Responsible Party): Percheron Therapeutics

Tracking Information

• First Submitted Date: June 5, 2023
• First Posted Date: July 10, 2023
• Last Update Posted Date: March 18, 2024
• Actual Study Start Date: May 18, 2023
• Estimated Primary Completion Date: November 13, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 29, 2023)

• 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 29, 2023)

• 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.
• 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). [ Time Frame: 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 [ Time Frame: 65 weeks ]
  Pharmacokinetic evaluation to evaluate dose response
• Area under the plasma concentration time curve (AUC) for ATL1102 over multiple timepoints [ Time Frame: 65 weeks ]
  Pharmacokinetic evaluation to evaluate dose concentration over time
• Time to Cmax and Cmin for ATL1102 over multiple timepoints [ Time Frame: 65 weeks ]
  Pharmacokinetic evaluation to evaluate concentration of ATL1102
• The terminal half life for ATL1102 [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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). [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: June 29, 2023)

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.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

randomized, double-blind, placebo controlled treatment periods followed by open labelled treatment period

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Duchenne Muscular Dystrophy

Intervention

• Drug: ATL1102 25mg
  Dose and scheduled as specified in the Arm description
• Drug: ATL1102 50mg
  Dose and scheduled as specified in the Arm description
• Drug: Placebo
  Dose and scheduled as specified in the Arm description

Study Arms

• Experimental: ATL1102 25mg
  ATL1102 25mg administered subcutaneously once weekly
  Intervention: Drug: ATL1102 25mg
• Experimental: ATL1102 50mg
  ATL1102 50mg administered subcutaneously once weekly
  Intervention: Drug: ATL1102 50mg
• Placebo Comparator: Placebo
  Placebo is administered subcutaneously once weekly
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 29, 2023): 45
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 5, 2025
• Estimated Primary Completion Date: November 13, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: DMD is a disease that predominantly affects males

• Ages: 10 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Percheron Therapeutics; +61 3 9827 8999; clinicaltrials@percherontx.com

Contact: Susan Turner

• Listed Location Countries: Australia, Bulgaria, Serbia, Turkey, United Kingdom

Administrative Information

• NCT Number: NCT05938023
• Other Study ID Numbers: 1102-DMD-Pre-CT03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Percheron Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Percheron Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Thomas Voit; UCL Great Ormond Street Institute of Child Health

• PRS Account: Percheron Therapeutics
• Verification Date: March 2024