Genetic Diseases, Inborn, Genetic Diseases, X-Linked, Muscular Diseases, Muscular Disorders, Atrophic, Muscular Dystrophies, Muscular Dystrophy, Duchenne, Nervous System Diseases, Neuromuscular Diseases
Conditions
Keywords
Duchenne Muscular Dystrophy, Cell Therapy, Performance of the Upper Limb, Pulmonary Function, Ambulatory, Non-Ambulatory, Glucocorticoids
Brief summary
HOPE-2 is a double-blind clinical trial evaluating the safety and efficacy of a cell therapy called CAP-1002 in study participants with Duchenne Muscular Dystrophy (DMD). Non-ambulatory and ambulatory boys and young men who meet eligibility criteria will be randomly assigned to receive either CAP-1002 or placebo every 3 months for a total of 4 doses during a 12-month period.
Detailed description
* Approximately 20 eligible study participants will be randomized to either CAP-1002 or placebo in a 1:1 ratio. * The trial will include visits at Screening, Baseline/Day 1, Week 4, and Months 3, 6, 9, and 12 with IV infusions of CAP-1002 or placebo on Day 1 and Months 3, 6, and 9. * Safety evaluations will include adverse events, concomitant medications, physical exam, vital signs, 12-lead ECG, and clinical laboratory testing. * Efficacy will be evaluated by Performance of the Upper Limb, cardiac MRI, pulmonary function testing, North Star Ambulatory Assessment (ambulatory subjects only), strength testing, and quality of life. * If trial data suggests an appropriate risk/benefit profile of CAP-1002, Capricor, upon the recommendation of the Data Safety Monitoring Board (DSMB), will introduce an open-label extension study to offer CAP-1002 to study participants who were randomized to placebo and completed all trial visits during the 12-month period.
Interventions
BIOLOGICALCAP-1002
The active pharmaceutical ingredient in CAP-1002 is Cardiosphere-Derived Cells (CDCs). CDCs are known to secrete numerous bioactive elements (growth factors, exosomes) which impact the therapeutic benefits of the cell-based therapy. The mechanism of action is the composite ability to be immunomodulatory, anti-fibrotic, anti-inflammatory, and pro-angiogenic.
DRUGPlacebo
Placebo
Sponsors
Capricor Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male participants at least 10 years of age at time of consent 2. Participants 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. Participants with diagnosis of DMD based on clinical and phenotypic manifestations consistent with DMD (e.g., family history of DMD, elevated creatine kinase, dystrophin muscle biopsy, calf pseudohypertrophy, Gowers' sign, and gait impairment before 7 years of age) with confirmatory genetic testing performed at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. 4. Participants with performance of the Upper Limb entry item score 2-5 5. Participants if ambulatory, 10-meter walk/run velocity \< 1 meter/second 6. Participants with loss of independent ambulation by 18th birthday (standing unassisted or ability to take, at most, several steps independently is not considered ambulation) 7. Participants who receiving standard of care therapy at an experienced, multidisciplinary, DMD center as evidenced by regular cardiac and pulmonary monitoring, systemic glucocorticoid treatment, and at-home range of motion exercises 8. Participants who received treatment with a systemic glucocorticoid is required for at least 12 months prior to randomization. The dose must remain stable for at least 6 months prior to randomization with the exception of either weight-based dose adjustment or a decrease in steroid dose of ≤ 10% for toxicity. For patients on chronic deflazacort, treatment with an equivalent dose of prednisone or prednisolone for a period of ≤ 30 days to bridge lack of availability of deflazacort during the 6 months prior to randomization is acceptable 9. Participants with current and up-to-date immunizations according to children and adolescent Centers for Disease Control immunization schedule, unless contraindicated, including the following: meningococcal and meningococcal B; tetanus, diphtheria & acellular pertussis (Tdap); and pneumococcal polysaccharide vaccinations 10. Participants with adequate venous access for parenteral IP infusions and routine blood collections in the judgement of the Investigator 11. Participants assessed by the Investigator as willing and able to comply with the requirements of the trial
Exclusion criteria
1. Participants with Left Ventricular Ejection Fraction (LVEF) \< 35% 2. Participants with elbow-flexion contractures \> 30° in both extremities 3. Participants with Body Mass Index (BMI) \> 45 4. Participants with documentation of exon 44 skip-amenable mutation(s) in the dystrophin gene 5. Participants with documentation of dystrophin deletion mutation(s) encompassing and limited to exons 3-7 6. Participants with percent predicted FVC (FVC%p) \< 35% 7. Participants with inability to perform consistent FVC measurement within ±15% during paired testing at screening 8. Participants with 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 at screening 9. Participants with history of non DMD-related chronic respiratory disease requiring ongoing or intermittent treatment, including, but not limited to, asthma, bronchitis, and tuberculosis 10. Participants with acute respiratory illness within 30 days prior to screening 11. Participants with initiation of non-invasive ventilation within 30 days prior to screening, or the anticipated need to initiate non-invasive ventilation within the 12 months following screening 12. Participants with planned or anticipated thoracic or spinal surgery within the 12 months following randomization 13. Participants with planned or anticipated lower extremity surgery within the 12 months following randomization, if ambulatory 14. Participants with known hypersensitivity to Dimethyl Sulfoxide (DMSO) or bovine products 15. Participants with initiation of treatment with metformin or insulin within 3 months prior to randomization 16. Participants with initiation of treatment with an FDA-approved exon skipping therapy for the treatment of DMD within 24 months prior to randomization or dose adjustments to the therapy within 12 months prior to randomization with the exception of weight-based dose adjustments. 17. Participants who received treatment with Human Growth Hormone (HGH) within 3 months prior to randomization, unless on a stable dose (as determined by the site PI) for at least 24 months prior to randomization 18. Participants who received Treatment with idebenone within 3 months prior to randomization 19. Participants who received treatment with a cell therapy product within 12 months prior to randomization 20. Participants who received treatment with an investigational product within 6 months prior to randomization 21. Participants with history, or current use, of drugs or alcohol that could impair their ability to comply with participation in the trial 22. Participants with 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 With Hypersensitivity Reactions | Baseline through Month 12 | Hypersensitivity reaction was defined as a clinical syndrome including, but not limited to, fever, leukocytosis, or rash with onset less than or equal to (\<=) 2 hours post-infusion and lasting less than (\<) 24 hours, in the absence of clinical signs of concomitant infection. |
| Change From Baseline in Functional Capacity as Assessed by the Mid-level (Elbow) Dimension Score of the Performance of Upper Limb (PUL) Version 1.2 at Month 12 | Baseline, Month 12 | Change from baseline in functional capacity as assessed by the mid-level (elbow) dimension of PUL version 1.2 at Month 12 expressed as percentile ranked change. PUL 1.2 scale assesses motor performance in the upper limb. PUL 1.2 included 22 items. One entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (score 0 to 16); Elbow Level (score 0 to 34); Distal Level Dimension (score 0 to 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
| Number of Participants Experiencing Acute Respiratory Decompensation | Baseline through Month 12 | Acute respiratory decompensation was defined as an unexplained rapid deterioration of the participant's condition with increasing shortness of breath requiring oxygen supplementation. |
| Number of Participants With Serious Adverse Events (SAEs) | Baseline through Month 12 | A SAE was 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 All-cause Mortality | Baseline through Month 12 | Number of participants who died due to any cause were reported. |
| Number of Participants With Immune Sensitization Syndrome | Baseline through Month 12 | Immune sensitization syndrome is defined as a) clinical signs and symptoms that are consistent with systemic inflammation (e.g.,fever, leukocytosis, rash, arthralgia), with an onset \>=24 hours after infusion of the investigational product, in the absence of clinical signs of concomitant infection, and b) an elevation of anti-Human Leukocyte Antigen (anti-HLA) antibodies against the Donor-Specific Antibody (DSA) cells, which is detected \<=30 days after the onset of syndrome, that meets the following criteria: i) 2000 mean fluorescence intensity if mean fluorescence intensity is \<=1000 at baseline, or ii) \>=2 times the baseline value. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product (IP) or Administration Procedure | Baseline through Month 12 | TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. The Investigator assessed the relationship (causality) of an AE to the investigational product and administration procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Baseline, Months 6 and 12 | Change from baseline in regional systolic LV wall thickening (anterior, lateral, inferior, septal) expressed as percentile ranked change, as assessed by cardiac MRI at Months 6 and 12. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
| Number of Participants With TEAEs and Severity of TEAEs | Baseline through Month 12 | TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. Severity of TEAEs were determined by following criteria:: Mild (Grade 1): Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required; Moderate (Grade 2): Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required; Severe (Grade 3): Marked limitation in activity, some assistance usually required; medical intervention/therapy required and often requiring hospitalization or prolongation of hospitalization; Life-Threatening or Disabling (Grade 4): Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required; hospitalization, prolongation of hospitalization, or hospice care; Fatal (Grade 5): death. |
| Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | Baseline, Months 3, 6, and 9 | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 expressed as percentile ranked change. PUL 1.2 scale assesses motor performance in the upper limb. PUL 1.2 included 22 items. One entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (score 0 to 16); Elbow Level (score 0 to 34); Distal Level Dimension (score 0 to 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Month 6 and 12 | Change from baseline in Left Ventricular Ejection Fraction assessed by cardiac magnetic resonance imaging (MRI) and expressed as percentile ranked change. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
| Change From Baseline in Left Ventricular End-Systolic Volume (Indexed) at Month 6 and 12 | Month 6 and 12 | Change from baseline in Left Ventricular End-systolic Volume (Indexed) assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. The End-systolic Volume (Indexed) (ESVI) is calculated as follows: ESVI= ESV (End-systolic Volume)/BSA (body surface area) = xxx mL/m\^2. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
| Change From Baseline in Left Ventricular End-Systolic Volume at Month 6 and 12 | Month 6 and 12 | Change from baseline in Left Ventricular End-systolic Volume assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
| Change From Baseline in Left Ventricular End-Diastolic Volume (Indexed) at Month 6 and 12 | Month 6 and 12 | Change from baseline in Left Ventricular End-diastolic Volume (Indexed) assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. The End-diastolic Volume (Indexed) (EDVI) is calculated as follows: EDVI= EDV (End-diastolic Volume)/BSA (body surface area) = xxx mL/m\^2. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
| Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12 | Month 6 and 12 | Change from baseline in Left Ventricular End-diastolic Volume assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times). |
Countries
United States
Participant flow
Recruitment details
Participants took part in this study at 7 investigational sites in the United States from 04 April 2018 to 10 March 2020.
Pre-assignment details
A total of 26 participants were screened, of these, 6 participants were deemed screen failures. Overall, 20 participants were randomized to receive CAP-1002 or placebo in this study.
Participants by arm
| Arm | Count |
|---|---|
| CAP-1002 Participants received CAP-1002 at a dose of 150 million Cardiosphere-Derived Cells (CDCs) via intravenous infusion, every 3 months on Day 1 and at Months 3, 6, and 9. | 8 |
| Placebo Participants received a CAP-1002 matching placebo via intravenous infusion, every 3 months on Day 1 and at Months 3, 6, and 9. | 12 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Other | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | CAP-1002 |
|---|---|---|---|
| Age, Continuous | 14.4 years STANDARD_DEVIATION 3.03 | 14.3 years STANDARD_DEVIATION 3.11 | 14.1 years STANDARD_DEVIATION 3.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 18 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 15 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 20 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 12 |
| other Total, other adverse events | 7 / 8 | 12 / 12 |
| serious Total, serious adverse events | 2 / 8 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Functional Capacity as Assessed by the Mid-level (Elbow) Dimension Score of the Performance of Upper Limb (PUL) Version 1.2 at Month 12
Change from baseline in functional capacity as assessed by the mid-level (elbow) dimension of PUL version 1.2 at Month 12 expressed as percentile ranked change. PUL 1.2 scale assesses motor performance in the upper limb. PUL 1.2 included 22 items. One entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (score 0 to 16); Elbow Level (score 0 to 34); Distal Level Dimension (score 0 to 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Baseline, Month 12
Population: ITT population included participants who were randomized. Here, overall number of participants signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| CAP-1002 | Change From Baseline in Functional Capacity as Assessed by the Mid-level (Elbow) Dimension Score of the Performance of Upper Limb (PUL) Version 1.2 at Month 12 | 65.5 Percentile Rank | Standard Error 10.82 |
| Placebo | Change From Baseline in Functional Capacity as Assessed by the Mid-level (Elbow) Dimension Score of the Performance of Upper Limb (PUL) Version 1.2 at Month 12 | 29.3 Percentile Rank | Standard Error 9.23 |
Primary
Number of Participants Experiencing Acute Respiratory Decompensation
Acute respiratory decompensation was defined as an unexplained rapid deterioration of the participant's condition with increasing shortness of breath requiring oxygen supplementation.
Time frame: Baseline through Month 12
Population: ITT population included participants who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants Experiencing Acute Respiratory Decompensation | 0 Participants |
| Placebo | Number of Participants Experiencing Acute Respiratory Decompensation | 0 Participants |
Primary
Number of Participants With All-cause Mortality
Number of participants who died due to any cause were reported.
Time frame: Baseline through Month 12
Population: Safety population included all participants who received investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With All-cause Mortality | 0 Participants |
| Placebo | Number of Participants With All-cause Mortality | 0 Participants |
Primary
Number of Participants With Hypersensitivity Reactions
Hypersensitivity reaction was defined as a clinical syndrome including, but not limited to, fever, leukocytosis, or rash with onset less than or equal to (\<=) 2 hours post-infusion and lasting less than (\<) 24 hours, in the absence of clinical signs of concomitant infection.
Time frame: Baseline through Month 12
Population: ITT population included participants who were randomized.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With Hypersensitivity Reactions | 3 Participants |
| Placebo | Number of Participants With Hypersensitivity Reactions | 0 Participants |
Primary
Number of Participants With Immune Sensitization Syndrome
Immune sensitization syndrome is defined as a) clinical signs and symptoms that are consistent with systemic inflammation (e.g.,fever, leukocytosis, rash, arthralgia), with an onset \>=24 hours after infusion of the investigational product, in the absence of clinical signs of concomitant infection, and b) an elevation of anti-Human Leukocyte Antigen (anti-HLA) antibodies against the Donor-Specific Antibody (DSA) cells, which is detected \<=30 days after the onset of syndrome, that meets the following criteria: i) 2000 mean fluorescence intensity if mean fluorescence intensity is \<=1000 at baseline, or ii) \>=2 times the baseline value.
Time frame: Baseline through Month 12
Population: Safety population included all participants who received investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With Immune Sensitization Syndrome | 0 Participants |
| Placebo | Number of Participants With Immune Sensitization Syndrome | 0 Participants |
Primary
Number of Participants With Serious Adverse Events (SAEs)
A SAE was 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: Baseline through Month 12
Population: Safety population included all participants who received investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With Serious Adverse Events (SAEs) | 2 Participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs) | 0 Participants |
Primary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product (IP) or Administration Procedure
TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. The Investigator assessed the relationship (causality) of an AE to the investigational product and administration procedure.
Time frame: Baseline through Month 12
Population: Safety population included all participants who received investigational product.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| CAP-1002 | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product (IP) or Administration Procedure | 5 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) Related to Investigational Product (IP) or Administration Procedure | 5 Participants |
Secondary
Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12
Change from baseline in regional systolic LV wall thickening (anterior, lateral, inferior, septal) expressed as percentile ranked change, as assessed by cardiac MRI at Months 6 and 12. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Baseline, Months 6 and 12
Population: ITT population included participants who were randomized. Here, overall number of participants signifies those participants who were evaluable for this outcome measure and 'number analyzed' signifies participants evaluable for specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Inferior LV at Month 6 | 57.3 Percentile Rank | Standard Error 12.37 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Anterior LV at Month 6 | 46.3 Percentile Rank | Standard Error 10.84 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Inferior LV at Month 12 | 60.3 Percentile Rank | Standard Error 10.99 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Lateral LV at Month 6 | 50.4 Percentile Rank | Standard Error 18.47 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Septal LV at Month 6 | 50.1 Percentile Rank | Standard Error 16.89 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Anterior LV at Month 12 | 40.9 Percentile Rank | Standard Error 8.9 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Septal LV at Month 12 | 50.8 Percentile Rank | Standard Error 15.28 |
| CAP-1002 | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Lateral LV at Month 12 | 49.2 Percentile Rank | Standard Error 17 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Septal LV at Month 12 | 49.9 Percentile Rank | Standard Error 12.97 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Anterior LV at Month 6 | 45.8 Percentile Rank | Standard Error 7.13 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Anterior LV at Month 12 | 40.7 Percentile Rank | Standard Error 8.88 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Lateral LV at Month 6 | 39.9 Percentile Rank | Standard Error 12.32 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Inferior LV at Month 6 | 59.7 Percentile Rank | Standard Error 8.52 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Inferior LV at Month 12 | 45.7 Percentile Rank | Standard Error 9.94 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Septal LV at Month 6 | 49.2 Percentile Rank | Standard Error 11.34 |
| Placebo | Change From Baseline in Regional Systolic Left Ventricular (LV) Wall Thickening, as Assessed by Cardiac Magnetic Resonance Imaging (MRI) at Months 6 and 12 | Systolic Wall Thickening Lateral LV at Month 12 | 27.4 Percentile Rank | Standard Error 14.26 |
Secondary
Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9
Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 expressed as percentile ranked change. PUL 1.2 scale assesses motor performance in the upper limb. PUL 1.2 included 22 items. One entry item to define the starting functional level, and 21 items subdivided into: Shoulder Level (score 0 to 16); Elbow Level (score 0 to 34); Distal Level Dimension (score 0 to 24). The total score range was from 0 to 74. For all items, the higher the score, the better the outcome. A negative change indicates worst the outcome. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Baseline, Months 3, 6, and 9
Population: ITT population included participants who were randomized. Here, overall number of participants signifies those participants who were evaluable for this outcome measure and 'number analyzed' signifies participants evaluable for specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | At Month 9 | 68.1 Percentile Rank | Standard Error 10.83 |
| CAP-1002 | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | At Month 3 | 86.6 Percentile Rank | Standard Error 10.51 |
| CAP-1002 | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | At Month 6 | 77.6 Percentile Rank | Standard Error 11.19 |
| Placebo | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | At Month 3 | 66.8 Percentile Rank | Standard Error 8.4 |
| Placebo | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | At Month 6 | 49.9 Percentile Rank | Standard Error 8.38 |
| Placebo | Change From Baseline in the Mid-level (Elbow) Dimension Score of the PUL 1.2 at Months 3, 6, and 9 | At Month 9 | 48.4 Percentile Rank | Standard Error 8.97 |
Secondary
Number of Participants With TEAEs and Severity of TEAEs
TEAE was defined as an AE that was not present prior to the initiation of line placement procedure for the IP infusion or was present but worsened in intensity or frequency. Severity of TEAEs were determined by following criteria:: Mild (Grade 1): Transient or mild discomfort; no limitation in activity; no medical intervention/therapy required; Moderate (Grade 2): Mild to moderate limitation in activity - some assistance may be needed; no or minimal medical intervention/therapy required; Severe (Grade 3): Marked limitation in activity, some assistance usually required; medical intervention/therapy required and often requiring hospitalization or prolongation of hospitalization; Life-Threatening or Disabling (Grade 4): Extreme limitation in activity, significant assistance required; significant medical intervention/therapy required; hospitalization, prolongation of hospitalization, or hospice care; Fatal (Grade 5): death.
Time frame: Baseline through Month 12
Population: Safety population included all participants who received investigational product. Here, overall number of participants signifies those participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CAP-1002 | Number of Participants With TEAEs and Severity of TEAEs | Participants with Severe (Grade 3) TEAEs | 1 participants |
| CAP-1002 | Number of Participants With TEAEs and Severity of TEAEs | Participants with Fatal (Grade 5) TEAEs | 0 participants |
| CAP-1002 | Number of Participants With TEAEs and Severity of TEAEs | Participants with Moderate (Grade 2) TEAEs | 4 participants |
| CAP-1002 | Number of Participants With TEAEs and Severity of TEAEs | Participants with TEAEs | 7 participants |
| CAP-1002 | Number of Participants With TEAEs and Severity of TEAEs | Participants with Life-threatening or Disabling (Grade 4) TEAEs | 1 participants |
| CAP-1002 | Number of Participants With TEAEs and Severity of TEAEs | Participants with Mild (Grade 1) TEAEs | 1 participants |
| Placebo | Number of Participants With TEAEs and Severity of TEAEs | Participants with Life-threatening or Disabling (Grade 4) TEAEs | 0 participants |
| Placebo | Number of Participants With TEAEs and Severity of TEAEs | Participants with Moderate (Grade 2) TEAEs | 5 participants |
| Placebo | Number of Participants With TEAEs and Severity of TEAEs | Participants with Severe (Grade 3) TEAEs | 1 participants |
| Placebo | Number of Participants With TEAEs and Severity of TEAEs | Participants with Mild (Grade 1) TEAEs | 6 participants |
| Placebo | Number of Participants With TEAEs and Severity of TEAEs | Participants with Fatal (Grade 5) TEAEs | 0 participants |
| Placebo | Number of Participants With TEAEs and Severity of TEAEs | Participants with TEAEs | 12 participants |
Other Pre-specified
Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12
Change from baseline in Left Ventricular Ejection Fraction assessed by cardiac magnetic resonance imaging (MRI) and expressed as percentile ranked change. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Month 6 and 12
Population: Intent-to-Treat (ITT) Population includes all participants who are randomized. Participants were summarized and analyzed in the treatment group to which they were randomized. Number analyzed signifies participants evaluable for specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Month 6 | 57.9 Percentile Rank | Standard Error 11 |
| CAP-1002 | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Month 12 | 54.5 Percentile Rank | Standard Error 9.08 |
| Placebo | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Month 6 | 34.9 Percentile Rank | Standard Error 7.46 |
| Placebo | Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 | Month 12 | 8.9 Percentile Rank | Standard Error 9.29 |
Other Pre-specified
Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12
Change from baseline in Left Ventricular End-diastolic Volume assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Month 6 and 12
Population: The ITT population includes all participants who are randomized. Participants were summarized and analyzed in the treatment group to which they were randomized. Number analyzed signifies participants evaluable for specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12 | Month 6 | 54.7 Percentile Rank | Standard Error 12.89 |
| CAP-1002 | Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12 | Month 12 | 49.2 Percentile Rank | Standard Error 12.55 |
| Placebo | Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12 | Month 6 | 33.4 Percentile Rank | Standard Error 8.87 |
| Placebo | Change From Baseline in Left Ventricular End-diastolic Volume at Month 6 and 12 | Month 12 | 48.6 Percentile Rank | Standard Error 11.81 |
Other Pre-specified
Change From Baseline in Left Ventricular End-Diastolic Volume (Indexed) at Month 6 and 12
Change from baseline in Left Ventricular End-diastolic Volume (Indexed) assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. The End-diastolic Volume (Indexed) (EDVI) is calculated as follows: EDVI= EDV (End-diastolic Volume)/BSA (body surface area) = xxx mL/m\^2. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Month 6 and 12
Population: The ITT population includes all participants who are randomized. Participants were summarized and analyzed in the treatment group to which they were randomized. Number analyzed signifies participants evaluable for specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in Left Ventricular End-Diastolic Volume (Indexed) at Month 6 and 12 | Month 6 | 34.8 Percentile Rank | Standard Error 14.11 |
| CAP-1002 | Change From Baseline in Left Ventricular End-Diastolic Volume (Indexed) at Month 6 and 12 | Month 12 | 12.2 Percentile Rank | Standard Error 13.29 |
| Placebo | Change From Baseline in Left Ventricular End-Diastolic Volume (Indexed) at Month 6 and 12 | Month 6 | 58.1 Percentile Rank | Standard Error 11.51 |
| Placebo | Change From Baseline in Left Ventricular End-Diastolic Volume (Indexed) at Month 6 and 12 | Month 12 | 60.0 Percentile Rank | Standard Error 12.27 |
Other Pre-specified
Change From Baseline in Left Ventricular End-Systolic Volume at Month 6 and 12
Change from baseline in Left Ventricular End-systolic Volume assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Month 6 and 12
Population: The ITT population includes all participants who are randomized. Participants were summarized and analyzed in the treatment group to which they were randomized. Number analyzed signifies participants evaluable for specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in Left Ventricular End-Systolic Volume at Month 6 and 12 | Month 6 | 48.4 Percentile Rank | Standard Error 12.16 |
| CAP-1002 | Change From Baseline in Left Ventricular End-Systolic Volume at Month 6 and 12 | Month 12 | 33.3 Percentile Rank | Standard Error 10.97 |
| Placebo | Change From Baseline in Left Ventricular End-Systolic Volume at Month 6 and 12 | Month 6 | 51.1 Percentile Rank | Standard Error 8.44 |
| Placebo | Change From Baseline in Left Ventricular End-Systolic Volume at Month 6 and 12 | Month 12 | 79.2 Percentile Rank | Standard Error 10.52 |
Other Pre-specified
Change From Baseline in Left Ventricular End-Systolic Volume (Indexed) at Month 6 and 12
Change from baseline in Left Ventricular End-systolic Volume (Indexed) assessed by cardiac magnetic resonance imaging (MRI) expressed as percentile ranked change. The End-systolic Volume (Indexed) (ESVI) is calculated as follows: ESVI= ESV (End-systolic Volume)/BSA (body surface area) = xxx mL/m\^2. Change from baseline and baseline values were converted to a percentile rank over all timepoints and at baseline using a non-parametric version of the prespecified model, generated by calculating the percentile rank of each change-from-baseline value relative to all observed change-from-baseline values for the same outcome (across all patients and all post-baseline observation times).
Time frame: Month 6 and 12
Population: The ITT population includes all participants who are randomized. Participants were summarized and analyzed in the treatment group to which they were randomized. Number analyzed signifies participants evaluable for specified timepoints.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| CAP-1002 | Change From Baseline in Left Ventricular End-Systolic Volume (Indexed) at Month 6 and 12 | Month 12 | 15.8 Percentile Rank | Standard Error 12.27 |
| CAP-1002 | Change From Baseline in Left Ventricular End-Systolic Volume (Indexed) at Month 6 and 12 | Month 6 | 38.6 Percentile Rank | Standard Error 12.96 |
| Placebo | Change From Baseline in Left Ventricular End-Systolic Volume (Indexed) at Month 6 and 12 | Month 6 | 50.2 Percentile Rank | Standard Error 10.73 |
| Placebo | Change From Baseline in Left Ventricular End-Systolic Volume (Indexed) at Month 6 and 12 | Month 12 | 68.9 Percentile Rank | Standard Error 11.77 |