Open-label Extension of the HOPE-2 Trial

Phase 2Active Not RecruitingNCT04428476

Capricor Inc.13 enrolled

Overview

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, over a period of approximately 60 months. Following completion of the initial open-label phase (Month 60), subjects who have completed all Month 60 assessments will be eligible to continue into a long-term open label extension (LT-OLE) period and can continue to receive deramiocel once every 3 months until deramiocel is commercially available or the sponsor terminates the study, or the subject withdraws consent or study participation is terminated by the sponsor. 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, 60, and all LT-OLE visits. 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, 57, and at all LT-OLE 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, 57, with continued dosing in the LT-OLE visits. 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.

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, over approximately a period of 60 months. Additional analyses of efficacy and safety will be conducted in the subsequent Long Term Open-Label Extension (LT-OLE) phase of the study. 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, 60, and all LT-OLE visits (± 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, and at all LT-OLE visits. 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, 57 trial visits. Continued dosing in the LT-OLE phase will begin at LT-OLE Visit 1, which may overlap with Month 60 of the initial OLE phase/LT-OLE Visit 1, in some cases. 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

Sex: ALLMin age: 10 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) From Baseline Through Month 12

Adverse event (AE) is defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.

Time frame: Baseline up to Month 12

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity From Baseline Through Month 12

Severity of adverse events (AE) were assessed by the investigator as Grade 1 = Mild (Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required), Grade 2 = Moderate (Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required), Grade 3 = Severe (Marked limitation in activity, some assistance usually required; medical intervention/therapy required and often requiring hospitalization or prolongation of hospitalization), Grade 4 = Life-threatening (Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required; hospitalization, prolongation of hospitalization, or hospice care) and Grade 5 = Death.

Time frame: Baseline up to Month 12

Change From Baseline in Functional Capacity as Assessed by Performance of the Upper Limb Test, Version 2 (PUL 2.0) Total Score.

PUL 2.0 scale is a 22-item scale used to assess the change that occurs in motor performance of the upper limb overtime from when a participant is still ambulant to the time participant loses all arm function when non-ambulant. PUL 2.0 includes an entry item to define broad starting functional level and 22 items subdivided into shoulder level (six items), mid-level (nine items), and distal level (seven items). Each dimension (shoulder, mid, distal) can be scored separately. There is maximum score of 12 for shoulder level, 17 for mid-level, and 13 for distal level. The total score was calculated by adding three level scores and ranged from 0-42. Higher score indicates better upper limb function.

Time frame: Baseline, Month 12

Secondary Outcomes

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) at Month 24, Month 36, Month 48 and Month 60

Time frame: Month 24, Month 36, Month 48 and Month 60

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity From Baseline Through Month 60

Time frame: Baseline up to Month 60

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

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

Time frame: Baseline, Month 12, Month 24, Month 36, Month 48, and Month 60

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