Open-label Extension of the HOPE-2 Trial

Study Overview
=================
Brief Summary
-----------------
This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will explore the safety and efficacy of sixteen intravenous administrations of CAP-1002, each separated by three months. Subjects will undergo a targeted screening during a 30-day screening period, eligible subjects will then undergo baseline safety and efficacy assessments on Day 1 prior to their first infusion of CAP-1002. Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45 and 48. Safety and efficacy assessments will be conducted prior to CAP-1002 administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45 trial visits, unless otherwise indicated. All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45. Subjects will be observed in the outpatient setting for at least two hours post infusion and then discharged the same day, if medically cleared by the site Investigator.

Detailed Description
-----------------
This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to subjects that were enrolled in the HOPE-2 trial and completed 12 months of follow-up. The trial will explore the safety and efficacy of sixteen intravenous administrations of CAP-1002, each separated by three months. Subjects will undergo a targeted screening during a 30-day screening period to determine eligibility based on protocol inclusion and exclusion criteria. Eligible subjects will undergo baseline safety and efficacy assessments on Day 1 prior to their first infusion of CAP-1002. Administration of CAP-1002 (Day 1) should occur within a maximum of 30 days following confirmation of eligibility. Subjects will complete trial assessments at Screening; Day 1; Months 3, 6, 9, 12 (± 14 days, each), 15, 18, 21, 24, 27, 30, 30, 33, 36, 39, 42, 45 and 48 (± 21 days, each). Safety and efficacy assessments will be conducted prior to CAP-1002 administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45 trial visits, unless otherwise indicated. All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site on Day 1 and Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42 and 45. Prior to each CAP-1002 administration, medications will be administered to the subject as determined by the Investigator based on the pre-treatment guidelines as outlined in the protocol and/or institutional protocols to minimize the risk of potential severe allergic reactions such as anaphylaxis. Subjects will be observed in the outpatient setting for at least two hours post infusion and then discharged the same day if medically cleared by the site Investigator. If clinically indicated, an unscheduled in-person visit will be performed at the investigative site with targeted assessments based on presentation of signs and symptoms following any infusion.

Official Title
-----------------
Open-Label Extension of the HOPE-2 Duchenne Muscular Dystrophy Trial

Conditions
-----------------
Duchenne Muscular Dystrophy

Intervention / Treatment
-----------------
* Biological: CAP-1002


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Documented enrollment in the HOPE-2 trial and completion of trial follow-up through Month 12 Willing and able to provide informed consent to participate in the trial if ≥ 18 years of age, and assent with parental or guardian informed consent if < 18 years of age Adequate venous access for intravenous CAP-1002 infusions in the judgement of the Investigator Assessed by the Investigator as willing and able to comply with the requirements of the trial Exclusion Criteria: Planned or likely major surgery in the next 12 months after planned first infusion Risk of near-term respiratory decompensation in the judgment of the investigator, or the need for initiation of non-invasive ventilator support as defined by serum bicarbonate ≥ 29 mmol/L History of non DMD-related chronic respiratory disease including, but not limited to, asthma, bronchitis, and tuberculosis Acute respiratory illness within 60 days prior to first infusion Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products Treatment with an investigational product ≤ 6 months prior to first infusion History, or current use, of drugs or alcohol that could impair ability to comply with participation in the trial Inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator

Ages Eligible for Study
-----------------
Minimum Age: 10 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label Extension of the HOPE-2 Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Open-label arm<br>Open-label CAP-1002 will be administered to all subjects enrolled in the trial | Biological: CAP-1002<br>* Peripheral infusion of 150 million allogeneic cardiosphere-derived cells administered every three months<br>* Other names: Allogeneic Cardiosphere-Derived Cells;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary safety endpoint is the incidence and severity of all treatment-emergent adverse events | Change from baseline in the incidence and severity of all treatment-emergent adverse events | At Month 12 timepoint | 
| The primary efficacy endpoint is change in upper limb function | Mean change from baseline in upper limb function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) Total Score. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation. | At Month 12 timepoint | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of all treatment-emergent adverse events | Change from baseline in the incidence and severity of all treatment-emergent adverse events | At Month 24, Month 36, and Month 48 timepoint | 
| Change from baseline in upper limb function | Mean change from baseline in upper limb function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) Total Score. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation. | At Month 24, Month 36, and Month 48 timepoint | 
| Change from from baseline in distal-level (wrist and hand) upper limb function | Mean change from baseline in distal-level (wrist and hand) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 2 and 3. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation. | At Month 12, Month 24, Month 36, and Month 48 timepoint | 
| Change from from baseline in mid-level (elbow) upper limb function | Mean change from baseline in mid-level (elbow) function assessed by Performance of the Upper Limb test, version 2 (PUL 2.0) for a subgroup of subjects with entry level scores of 4 and 5. Items are scored on a three-point scale: 0=unable to perform the item, 1=impaired or performs with compensation, 2=performs task without compensation. | At Month 12, Month 24, Month 36, and Month 48 timepoint | 
| Change in cardiac muscle function and structure by assessment of Left Ventricular Ejection Fraction (LVEF) | Mean change from baseline in LVEF as assessed by Cardiac Magnetic Resonance (cMRI) | At Month 24, Month 36, and Month 48 timepoint | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DMD, Muscular dystrophy, Duchenne