Duchenne Muscular Dystrophy
Conditions
Keywords
Duchenne Muscular Dystrophy, Cardiomyopathy, Duchenne
Brief summary
This Phase 2, multi-center, open-label extension trial will provide CAP-1002 to participants who were randomized to the Usual Care treatment group of the HOPE-Duchenne study (NCT02485938) and completed 12 months of follow-up. The trial will assess the safety and efficacy of two intravenous administrations of CAP-1002, each separated by three months.
Detailed description
Participants with documented enrollment in the Usual Care treatment group of the HOPE-Duchenne study and completion of study follow-up through Month 12 were eligible for this study. Participants 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. All CAP-1002 infusions will be conducted in an outpatient setting at the investigative site on Day 1 and at Month 3. Participants 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.
Interventions
Intravenous infusion delivery of Allogeneic Cardiosphere-Derived Cells (CAP-1002; 75 million CDCs)
Sponsors
Capricor Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Documented enrollment in the Usual Care Treatment Group of the HOPE-Duchenne trial and completion of trial follow-up through Month 12. 2. Willing and able to provide informed consent to participate in the trial if greater than or equal to (\>=) 18 years of age, and assent with parental or guardian informed consent if less than (\<) 18 years of age. 3. Adequate venous access for intravenous CAP-1002 infusions and routine blood collections 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. Left ventricular ejection fraction (LVEF) \< 35 percent (%) within 6 months of screening. 2. Planned or likely major surgery in the next 6 months after planned first infusion. 3. 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 millimoles per liter (mmol/L) at screening. 4. History of non DMD-related chronic respiratory disease including, but not limited to, asthma, bronchitis, and tuberculosis. 5. Acute respiratory illness within 30 days prior to screening. 6. Known hypersensitivity to dimethyl sulfoxide (DMSO) or bovine products. 7. Treatment with investigational product \<= 6 months prior to first infusion. 8. History, or current use, of drugs or alcohol that could impair ability to comply with participation in the trial. 9. Inability to comply with the investigational plan and follow-up visit schedule for any reason, in the judgment of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Acute Respiratory Decompensation | 2 hours post-dose on Day 1 and Month 3 | Acute respiratory decompensation is defined as an unexplained rapid deterioration of the participant's condition with increasing shortness of breath requiring oxygen supplementation. Acute respiratory decompensation within 2 hours following investigational product (IP) administration will be reported. |
| Number of Participants With Hypersensitivity Reactions | From Day 1 up to Month 6 | Hypersensitivity reaction is defined as a clinical syndrome including, but not limited to, fever, leukocytosis, or rash with onset \<= 2 hours post-infusion and lasting \< 24 hours, in the absence of clinical signs of concomitant infection. |
| All-cause Mortality | From Day 1 up to Month 6 | Number of deaths due to any cause will be reported. |
| Number of Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product or Administration and Serious Adverse Events (SAEs) | From Day 1 up to Month 6 | An adverse events (AEs) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs occurring after the initiation of the IV catheter placement for the initial dose of IP. TEAEs related to investigational product or administration are reported for this outcome measure. A SAE is defined as an AE that results in any of the following outcomes: Death; life-threatening adverse event; Inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect. |
| Number of Participants With Immune Sensitization Syndrome | From Day 1 up to Month 6 | Immune sensitization syndrome shall be defined as: (a) clinical signs and symptoms consistent with systemic inflammation (e.g., fever, leukocytosis, rash, or arthralgia) with onset \>= 24 hours post infusion and the absence of clinical signs of concomitant infection, and (b) elevation of anti-human leukocyte antigen (HLA) antibodies against the donor cells (i.e., DSAs), detected \<= 30 days following onset of syndrome, of (i) \>= 2000 mean fluorescent intensity (MFI) if baseline MFI \<= 1000, or (ii) \>= 2 times baseline otherwise. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CAP-1002 All participants who were randomized to the Usual Care Treatment Group and completed 12 months of follow-up in the HOPE-Duchenne trial (NCT02485938), and received CAP-1002 intravenous infusion on Day 1 and at Month 3 in the current study. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | CAP-1002 |
|---|---|
| Age, Continuous | 19.8 years STANDARD_DEVIATION 2.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 8 |
| other Total, other adverse events | 7 / 8 |
| serious Total, serious adverse events | 1 / 8 |
Outcome results
Primary
All-cause Mortality
Number of deaths due to any cause will be reported.
Time frame: From Day 1 up to Month 6
Population: Analysis was performed on safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | All-cause Mortality | 0 Participants |
Primary
Number of Participants Experiencing Acute Respiratory Decompensation
Acute respiratory decompensation is defined as an unexplained rapid deterioration of the participant's condition with increasing shortness of breath requiring oxygen supplementation. Acute respiratory decompensation within 2 hours following investigational product (IP) administration will be reported.
Time frame: 2 hours post-dose on Day 1 and Month 3
Population: Analysis was performed on safety population that included all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| CAP-1002 | Number of Participants Experiencing Acute Respiratory Decompensation | Day 1 | 0 Participants |
| CAP-1002 | Number of Participants Experiencing Acute Respiratory Decompensation | Month 3 | 0 Participants |
Primary
Number of Participants With Hypersensitivity Reactions
Hypersensitivity reaction is defined as a clinical syndrome including, but not limited to, fever, leukocytosis, or rash with onset \<= 2 hours post-infusion and lasting \< 24 hours, in the absence of clinical signs of concomitant infection.
Time frame: From Day 1 up to Month 6
Population: Analysis was performed on safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With Hypersensitivity Reactions | 1 Participants |
Primary
Number of Participants With Immune Sensitization Syndrome
Immune sensitization syndrome shall be defined as: (a) clinical signs and symptoms consistent with systemic inflammation (e.g., fever, leukocytosis, rash, or arthralgia) with onset \>= 24 hours post infusion and the absence of clinical signs of concomitant infection, and (b) elevation of anti-human leukocyte antigen (HLA) antibodies against the donor cells (i.e., DSAs), detected \<= 30 days following onset of syndrome, of (i) \>= 2000 mean fluorescent intensity (MFI) if baseline MFI \<= 1000, or (ii) \>= 2 times baseline otherwise.
Time frame: From Day 1 up to Month 6
Population: Analysis was performed on safety population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With Immune Sensitization Syndrome | 0 Participants |
Primary
Number of Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product or Administration and Serious Adverse Events (SAEs)
An adverse events (AEs) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as AEs occurring after the initiation of the IV catheter placement for the initial dose of IP. TEAEs related to investigational product or administration are reported for this outcome measure. A SAE is defined as an AE that results in any of the following outcomes: Death; life-threatening adverse event; Inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Time frame: From Day 1 up to Month 6
Population: Analysis was performed on safety population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAP-1002 | Number of Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product or Administration and Serious Adverse Events (SAEs) | TEAEs | 11 number of events |
| CAP-1002 | Number of Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product or Administration and Serious Adverse Events (SAEs) | TESAEs | 1 number of events |