Clinical trial NCT04428476: Open-label Extension of the HOPE-2 Trial
Official title: Open-Label Extension of the HOPE-2 Duchenne Muscular Dystrophy Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Duchenne Muscular Dystrophy
Keywords: DMD, Muscular dystrophy, Duchenne
Lead sponsor: Capricor Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-11
Enrollment: 13
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label Extension of the HOPE-2 Trial
Primary purpose: TREATMENT

Brief summary: This Phase 2, multi-center, open-label extension trial will provide deramiocel (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 twenty intravenous administrations of deramiocel, 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 deramiocel.

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, 48, 51, 54, 57, and 60. Safety and efficacy assessments will be conducted prior to deramiocel administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, and 57 trial visits, unless otherwise indicated.

All deramiocel 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, 45, 48, 51, 54, and 57. 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 deramiocel (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 twenty intravenous administrations of deramiocel, 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 deramiocel. Administration of deramiocel (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, 48, 51, 54, 57, and 60 (± 21 days, each). Safety and efficacy assessments will be conducted prior to deramiocel administration at the Day 1, Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39, 42, 45, 48, 51, 54, and 57 trial visits, unless otherwise indicated.

All deramiocel 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, 45, 48, 51, 54, and 57. Prior to each deramiocel 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.

Eligibility criteria: Inclusion Criteria:

1. Documented enrollment in the HOPE-2 trial and completion of trial follow-up through Month 12
2. 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
3. Adequate venous access for intravenous deramiocel (CAP-1002) infusions in the judgement of the Investigator
4. Assessed by the Investigator as willing and able to comply with the requirements of the trial

Exclusion Criteria:

1. Planned or likely major surgery in the next 12 months after planned first infusion
2. 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
3. History of non DMD-related chronic respiratory disease including, but not limited to, asthma, bronchitis, and tuberculosis
4. Acute respiratory illness within 60 days prior to first infusion
5. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products
6. Treatment with an investigational product ≤ 6 months prior to first infusion
7. History, or current use, of drugs or alcohol that could impair ability to comply with participation in the trial
8. Inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Month 12
timeFrame: Baseline up to Month 12
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity From Baseline Through Month 12
timeFrame: Baseline up to Month 12
measure: Change From Baseline in Functional Capacity as Assessed by Performance of the Upper Limb Test, Version 2 (PUL 2.0) Total Score.
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) at Month 24, Month 36, Month 48 and Month 60
timeFrame: Month 24, Month 36, Month 48 and Month 60
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity From Baseline Through Month 60
timeFrame: Baseline up to Month 60
measure: Change From Baseline in Upper Limb Function as Assessed by Performance of the Upper Limb Test, Version 2 (PUL 2.0) at Month 12, Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Distal-Level (Wrist and Hand) Upper Limb Function as Assessed by Performance of the Upper Limb Test, Version 2 (PUL 2.0) at Month 12, Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Mid-Level (Elbow) as Assessed by Performance of the Upper Limb Test, Version 2 (PUL 2.0) at Month 12, Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Left Ventricular Ejection Fraction (LVEF) at Month, 24, 36, 48, and 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Left Ventricular End Systolic Volumes-Indexed (LV-ESVI) at Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Left Ventricular End Diastolic Volumes-Indexed (LV-EDVI) at Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Left Ventricle Mass (LV Mass) at Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Unindexed Volumes at Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Left Ventricle End Diastolic Wall Thickening (LVEDWT) at Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
measure: Change From Baseline in Cardiac Parameter: Left Ventricle End Systolic Wall Thickening (LVESWT) at Month 24, Month 36, Month 48, and Month 60
timeFrame: Baseline, Month 24, Month 36, Month 48, and Month 60
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Milwaukee
country: United States
facility: Children's Hospital Wisconsin
state: Wisconsin
Study officials:
affiliation: UC Davis
name: Craig McDonald, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Capricor Inc.
name: Mark Awadalla
role: STUDY_DIRECTOR
References: