Hypertension,Pulmonary
Conditions
Brief summary
The SAPPHIRE clinical trial seeks to establish the efficacy and safety of repeated monthly dosing of autologous EPCs transfected with human eNOS (heNOS) in patients with symptomatic severe PAH on available PAH-targeted medical therapy.
Detailed description
SAPPHIRE will use autologous progenitor cell-based gene delivery to enhance lung microvascular repair and regeneration in patients with severe symptomatic PAH. A total of 45 patients will be enrolled in this multi-centre, late phase, randomized, double-blind, placebo-controlled, 3-arm protocol. Up to nine centres across Canada will participate. Consented study participants who meet all eligibility criteria during the screening period will be scheduled to undergo apheresis. Following successful apheresis collection and receipt of the cell samples by the cell manufacturing facility, randomization will take place though a web-based system. Manufacturing of the cell therapy product will then be performed by the cell manufacturing facility according to the assigned treatment allocation: Arm 1: Placebo (Plasma-Lyte A; 4 monthly IV infusions) in Course 1 (1st 6 months) followed by Autologous EPCs transfected with human eNOS in Course 2 (2nd 6 months; 4 monthly IV infusions) Arm 2: Autologous EPCs transfected with human eNOS in Course 1 (1st 6 months; 4 monthly IV infusions) followed by Placebo (Plasma-Lyte A) in Course 2 (2nd 6 months; 4 monthly IV infusions) Arm 3: Autologous EPCs transfected with human eNOS in Course 1 (1st 6 months; 4 monthly IV infusions) followed by a repeat dosing with Autologous EPCs transfected with human eNOS in Course 2 (2nd 6 months; 4 monthly IV infusions) Approximately 5-9 days later, the study product will be transported to the investigative site where the initial treatment will be delivered to the study participant in an outpatient setting which is equipped for continuous monitoring of vital signs and oxygen saturation. Participants will subsequently be monitored for a minimum of 1 hour and discharged from the clinic once judged by the study investigator to be clinically stable. Treatment and follow-up assessments will take place over a 12-month period (11 study visits in total). Once the 12-month trial data collection is completed, the trial will convert to a registry with the goal of collecting long-term safety information through annual telephone contacts for 10 years. Participants will be permitted to enroll in other clinical trials during the registry period.
Interventions
BIOLOGICALPlacebo followed by Autologous EPCs transfected with human eNOS
4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months
BIOLOGICALAutologous EPCs transfected with human eNOS followed by Placebo
4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months
4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months
Sponsors
Ottawa Hospital Research Institute
Northern Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years, ≤ 80 years * Established diagnosis of PAH due to the following: * Idiopathic or heritable PAH; * Scleroderma associated PAH (limited or diffuse); * Drugs (anorexigens) or toxins; * Congenital heart defects (atrial septal defects, ventricular septal defects, and patent ductus arteriosus) repaired ≥ 1 years * World Health Organization (WHO) functional class II, III, or IV on appropriate stable therapy for PAH for at least 3 months prior to the screening period and up until randomization, apart from modification of anticoagulant or diuretic dosages, or small adjustments in prostaglandin dose that are considered by the Investigator to be consistent with stable parenteral therapy. * Able to walk unassisted (oxygen use allowed). Aids for carrying oxygen (such as a wheel chair or walker) are permitted provided they are not also required as mobility aids. * An average 6-Minute Walk Distance (6MWD) of ≥ 125 meters and ≤ 440 meters on two consecutive tests during the Screening period * Previous diagnostic right heart cardiac catheterization (RHC) at the time of PAH diagnosis with findings consistent with PAH: specifically, mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg (at rest); pulmonary vascular resistance (PVR) ≥ 3 WU; pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤12 mmHg if PVR ≥ 3 to \< 5 Woods Units (WU), or pulmonary capillary wedge pressure (PCWP) (or left ventricular end diastolic pressure) ≤ 15 mmHg if PVR ≥ 5 WU. If repeat testing has occurred since initial diagnosis, the most recent results should be used. * Echocardiography performed within 12 months prior to the Screening Period confirming a left atrial volume index (LAVI) of ≤ 34 ml/m2 and the absence of any clinically significant left heart disease including evidence of more than mild left-sided valvular heart disease, systolic or diastolic left ventricular dysfunction * Ventilation and perfusion (VQ) nuclear scan performed as part of the initial workup to establish the diagnosis of PAH showing absence (i.e. low probability) of pulmonary embolism. If repeat testing has occurred since initial diagnosis, the most recent results should be used. In the absence of a VQ scan to establish eligibility, a CT angiogram that has been reviewed by a radiologist with expertise in the work up for pulmonary endarterectomy and deemed negative for chronic thromboembolic disease may be used instead. * Pulmonary function tests conducted within 2 years prior to the Screening Period to confirm: total lung capacity (TLC) ≥ 65% the predicted value; and forced expiratory volume at one second (FEV1) of ≥ 65% the predicted value * Must have a resting arterial oxygen saturation (SaO2) ≥88% with or without supplemental oxygen as measured by pulse oximetry at the Screening Visit * Must not be enrolled in an exercise training program for pulmonary rehabilitation within 3 months prior to the Screening Visit and must agree not to enroll in an exercise training program for pulmonary rehabilitation during the Screening Period and the first 6 months of the study. Participants enrolled in an exercise program for pulmonary rehabilitation 3 months prior to screening may enter the study if they agree to maintain their current level of rehabilitation for the first 6 months of the study * Women of child-bearing potential (defined as less than 1 year post-menopausal and not surgically sterile) must be practicing abstinence or using two highly effective methods of contraception (defined as a method of birth control that results in a low failure rate, i.e., less than 1% per year, such as approved hormonal contraceptives, barrier methods \[such as a condom or diaphragm\] used with a spermicide, or an intrauterine device). Subjects must have a negative ß-human chorionic gonadotropin (hCG) pregnancy test during the Screening period and negative urine pregnancy test results at all other study visits * Must be willing and able to comply with study requirements and restrictions.
Exclusion criteria
* Pregnant or lactating * PAH related to any condition not covered under inclusion criteria, including but not limited to pulmonary venous hypertension, pulmonary veno-occlusive disease, pulmonary capillary hemangiomatosis, or chronic thromboembolic pulmonary hypertension * Evidence of more than mild interstitial lung disease on Chest CT within the last 5 years (last 3 years for patients with scleroderma associated PAH) * Treatment with an investigational drug, device or therapy within 3 months prior to the screening period or is scheduled to receive an investigational drug, device or therapy during the course of the study * Any musculoskeletal disease or any other disease that would significantly limit ambulation * Unrepaired or recently repaired (\< 1 year) congenital systemic-to-pulmonary shunt other than patent foramen ovale * Patients having three or more of the following four AMBITION study heart failure preserved ejection fractio (HFpEF) risk factors will be excluded: * BMI ≥ 30 kg/m2, * History of essential hypertension, * Diabetes mellitus (any type) * Historical evidence of significant coronary artery disease (CAD) by any one of the following: * History of myocardial infarction (MI) * History of percutaneous coronary intervention (PCI) * Prior coronary angiography evidence of CAD (\>50% stenosis in ≥1 vessel) * Previous positive Stress Test * Previousoronary artery bypass grafting (CABG) * Stable angina * Creatinine clearance \<30 ml/min (using the Cockroft-Gault formula) or requires hemodialysis * Inability to undergo the apheresis procedure due to poor venous access or laboratory tests that are not within acceptable ranges (not including international normalized ratio (INR) for patients on Coumadin) * Childs-Pugh class C liver cirrhosis * Previous atrial septostomy * Any other clinically significant illness or abnormal laboratory values (measured during the screening period) that, in the opinion of the Investigator, might put the subject at risk of harm during the study or might adversely affect the interpretation of the study data * Anticipated survival less than 1 year due to concomitant disease * History of cancer in the past 5 years (except for low grade and fully resolved non-melanoma skin cancer) * Results during screening consistent with current infection with HIV, Hepatitis B (HBV) or C (HCV), human T-cell lymphotropic virus (HTLV- I/II) or syphilis * Systemic arterial systolic blood pressure \< 85 mm Hg * Known allergy to gentamicin or amphotericin * Patients who have participated in any gene therapy study or an angiogenic growth factor protein study * Patients unable to provide informed consent and comply with the visit schedule.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6 Minute Walk Distance (6MWD) From Baseline | Baseline, 6 months | Change was calculated as the distance walked at 6 months minus the distance at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6 Minute Walk Distance (6MWD) From Baseline | Baseline and 12 months | Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arms 2 versus Arm 3). Change was calculated by the distance walked at 12 months minus the distance walked at baseline. |
| Change in 6MWD From Baseline | Baseline, 6 months, 12 months | Incremental effect of 8 versus 4 doses at 6 and 12 months in arm 3 only. |
| Change in Pulmonary Vascular Resistance From Baseline | 6 months | Comparison of change from baseline after 4 doses of study product (Arms 2 and 3 versus Arm 1) |
| Incremental Effect of 8 Versus 4 Doses of Cell Therapy Product on PVR | 6 and12 months | Incremental effect of 8 versus 4 doses of cell therapy product on PVR at 6 and 12 months (Arm 3 only) |
| Change in Quality of Life Measures From Baseline | Baseline and 6 months | Comparison of change from baseline measured by the Short Form 36 (SF-36) Health Survey after delivery of 4 doses of study product (Arms 2 and 3 versus Arm 1). Scale used ranging from 0-100. Lower scores indicate more significant limitations. |
Countries
Canada
Participant flow
Recruitment details
Participants were recruited based on physician referral from specialized Pulmonary Arterial Hypertension clinics at 6 participating study sites between October 2017 and August 2022. The first participant was enrolled on November 24, 2017 and the last participant was enrolled on August 24, 2022.
Pre-assignment details
Of 22 enrolled participants, 12 met the required inclusion criteria and were randomized to receive treatment with the study product.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Followed by Autologous EPCs Transfected With eNOS 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 1 followed by 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 2
Placebo followed by Autologous EPCs transfected with human eNOS: 4 doses of placebo in first 6 months followed by 4 doses of autologous EPCs transfected with eNOS in second 6 months | 5 |
| Autologous EPCs Transfected With eNOS Followed by Placebo 4 monthly IV injections of Autologous EPCs transfected with human eNOS (total of 80 million cells) during Course 1 followed by 4 monthly IV injections of Placebo (Plasma-Lyte A) during Course 2
Autologous EPCs transfected with human eNOS followed by Placebo: 4 doses of autologous EPCs transfected with eNOS in first 6 months followed by 4 doses of placebo in second 6 months | 3 |
| Autologous EPCs Transfected With eNOS 4 monthly IV injections of Autologous EPCs transfected with human eNOS in Course 1 followed by 4 monthly injections of Autologous EPCs transfected with human eNOS in Course 2 (total of 160 million cells)
Autologous EPCs transfected with human eNOS: 4 doses of autologous EPCs transfected with eNOS in first 6 months which is repeated in second 6 months | 4 |
| Total | 12 |
Baseline characteristics
| Characteristic | Total | Placebo Followed by Autologous EPCs Transfected With eNOS | Autologous EPCs Transfected With eNOS Followed by Placebo | Autologous EPCs Transfected With eNOS |
|---|---|---|---|---|
| 6 Minute Walk Test Distance | 348.92 Meters STANDARD_DEVIATION 60.57 | 345.4 Meters STANDARD_DEVIATION 71.48 | 381.0 Meters STANDARD_DEVIATION 11.53 | 329.25 Meters STANDARD_DEVIATION 78.08 |
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 10.9 | 59.6 Years STANDARD_DEVIATION 15.4 | 48.7 Years STANDARD_DEVIATION 5.8 | 55 Years STANDARD_DEVIATION 4.3 |
| Cardiac Output | 5.13 L/min STANDARD_DEVIATION 1.49 | 5.39 L/min STANDARD_DEVIATION 1.36 | 4.55 L/min STANDARD_DEVIATION 0.41 | 5.25 L/min STANDARD_DEVIATION 2.26 |
| Comorbidities Asthma | 3 Participants | 2 Participants | 1 Participants | 0 Participants |
| Comorbidities Emphysema | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Comorbidities Gastrointestinal Reflux | 6 Participants | 2 Participants | 1 Participants | 3 Participants |
| Comorbidities Hypertension | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Comorbidities Hypothyroidism | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Comorbidities Morbid Obesity | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Comorbidities Obstructive Sleep Apnea | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Comorbidities Seasonal Allergies | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Comorbidities Type 2 Diabetes | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Concurrent Medications Dual Therapy | 6 Participants | 3 Participants | 1 Participants | 2 Participants |
| Concurrent Medications Endothelin Receptor Antagonist | 10 Participants | 3 Participants | 3 Participants | 4 Participants |
| Concurrent Medications PDE5 Inhibitor | 7 Participants | 4 Participants | 2 Participants | 1 Participants |
| Concurrent Medications Prostaglandin Intravenous | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Concurrent Medications Soluble GC Stimulator | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Concurrent Medications Triple Therapy | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Hemodynamic Parameters Mean pulmonary arterial pressure (PAP) (mmHg) | 78 mmHg STANDARD_DEVIATION 11 | 79 mmHg STANDARD_DEVIATION 13 | 74 mmHg STANDARD_DEVIATION 4 | 80 mmHg STANDARD_DEVIATION 15 |
| Hemodynamic Parameters PCWP (mmHg) | 9.9 mmHg STANDARD_DEVIATION 5.5 | 11 mmHg STANDARD_DEVIATION 6 | 9.7 mmHg STANDARD_DEVIATION 7.2 | 8.5 mmHg STANDARD_DEVIATION 4.8 |
| Oxygen Saturation | 94.3 Percent STANDARD_DEVIATION 3.3 | 93.4 Percent STANDARD_DEVIATION 3.7 | 95.0 Percent STANDARD_DEVIATION 3 | 95.0 Percent STANDARD_DEVIATION 3.6 |
| Pulmonary arterial hypertension (PAH) Diagnosis Congenital Heart Defects | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Pulmonary arterial hypertension (PAH) Diagnosis Drugs/Toxins | 3 Participants | 2 Participants | 0 Participants | 1 Participants |
| Pulmonary arterial hypertension (PAH) Diagnosis Idopathic/Hereditable | 7 Participants | 3 Participants | 2 Participants | 2 Participants |
| Pulmonary vascular resistance (PVR) | 7.19 WU STANDARD_DEVIATION 2.78 | 6.18 WU STANDARD_DEVIATION 2.87 | 7.87 WU STANDARD_DEVIATION 2.87 | 7.95 WU STANDARD_DEVIATION 3.26 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 10 Participants | 4 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Indigenous | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 10 Participants | 4 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 3 | 0 / 4 |
| other Total, other adverse events | 5 / 5 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 1 / 5 | 0 / 3 | 1 / 4 |
Outcome results
Primary
Change in 6 Minute Walk Distance (6MWD) From Baseline
Change was calculated as the distance walked at 6 months minus the distance at baseline.
Time frame: Baseline, 6 months
Population: All participants for whom the 6MWD test was completed at baseline and 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in 6 Minute Walk Distance (6MWD) From Baseline | 22.3 Meters | Standard Deviation 38.49 |
| Arm 2 and 3 During First 6 Months | Change in 6 Minute Walk Distance (6MWD) From Baseline | 36.00 Meters | Standard Deviation 31.11 |
Comparison: Due to sample size restriction, the primary analysis plan was modified to analyze change from baseline to each time point using repeated measures of ANOVA.p-value: 0.4295% CI: [-20.08, 47.48]ANOVA
Comparison: Calculation of raw change from baseline in meters using non-parametric Wilcoxon test.p-value: 0.57Wilcoxon (Mann-Whitney)
p-value: 0.53Wilcoxon (Mann-Whitney)
Secondary
Change in 6 Minute Walk Distance (6MWD) From Baseline
Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arms 2 versus Arm 3). Change was calculated by the distance walked at 12 months minus the distance walked at baseline.
Time frame: Baseline and 12 months
Population: All participants in Arm 2 and 3 for whom the 6MWD test results were recorded at baseline and 12 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in 6 Minute Walk Distance (6MWD) From Baseline | 49.3 Meters | Standard Deviation 11.68 |
| Arm 2 and 3 During First 6 Months | Change in 6 Minute Walk Distance (6MWD) From Baseline | 7.33 Meters | Standard Deviation 9.02 |
Comparison: Comparison of these arms is in accordance with the statistical analysis plan.p-value: 0.1Wilcoxon (Mann-Whitney)
Secondary
Change in 6 Minute Walk Distance (6MWD) From Baseline
Comparison of change from baseline to assess durability of any measured improvement (Arm 2 only). Durability of any improvement at 3 versus 9 months post-treatment (measured at 6 and 12 months).
Time frame: Baseline, 6 months, 12 months
Population: All participants in Arm 2 for whom the 6MWD test results were recorded at baseline, 6 months, and 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in 6 Minute Walk Distance (6MWD) From Baseline | Change from baseline to 6 months | 47.3 Meters | Standard Deviation 32.5 |
| Arm 1 - Placebo During First 6 Months | Change in 6 Minute Walk Distance (6MWD) From Baseline | Change from baseline to 12 months | 49.3 Meters | Standard Deviation 11.68 |
Comparison: The selected arm for this outcome measure is in accordance with the statistical analysis plan.p-value: 0.5Wilcoxon (Mann-Whitney)
Secondary
Change in 6MWD From Baseline
Incremental effect of 8 versus 4 doses at 6 and 12 months in arm 3 only.
Time frame: Baseline, 6 months, 12 months
Population: Change was calculated as the distance at 6 months minus the distance at baseline and the distance at 12 months minus the distance at baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in 6MWD From Baseline | Change from baseline to 6 months | 30.25 Meters | Standard Deviation 33.61 |
| Arm 1 - Placebo During First 6 Months | Change in 6MWD From Baseline | Change from baseline to 12 months | 7.33 Meters | Standard Deviation 9.02 |
Comparison: Selection of the arm for analysis of this outcome measure is in accordance with the statistical analysis plan.p-value: 0.88Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Vascular Resistance From Baseline
Comparison of change from baseline after 4 doses of study product (Arms 2 and 3 versus Arm 1)
Time frame: 6 months
Population: Participants in Arm 1 and Arm 2 and 3 combined for whom PVR was measured at baseline and 6 months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in Pulmonary Vascular Resistance From Baseline | 0.444 Wood Units (WU) | Standard Deviation 1.18 |
| Arm 2 and 3 During First 6 Months | Change in Pulmonary Vascular Resistance From Baseline | 0.576 Wood Units (WU) | Standard Deviation 2.07 |
Comparison: Selection of the arms for analysis of this outcome measure is in accordance with the statistical analysis plan.p-value: 0.81Wilcoxon (Mann-Whitney)
Secondary
Change in Pulmonary Vascular Resistance From Baseline
Comparison of change from baseline after delivery of 4 versus 8 doses of study product (Arm 2 versus Arm 3)
Time frame: Baseline and 12 months
Population: Participants in Arm 2 and Arm 3 for whom the PVR was measured at baseline and 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in Pulmonary Vascular Resistance From Baseline | 0.09 Wood Units (WU) | Standard Deviation 1.81 |
| Arm 2 and 3 During First 6 Months | Change in Pulmonary Vascular Resistance From Baseline | 2.15 Wood Units (WU) | Standard Deviation 3.09 |
Comparison: Selection of the arms for analysis of this outcome measure is in accordance with the statistical analysis plan.p-value: 0.63Wilcoxon (Mann-Whitney)
Secondary
Change in Quality of Life Measures From Baseline
Comparison of change from baseline measured by the Short Form 36 (SF-36) Health Survey after delivery of 4 doses of study product (Arms 2 and 3 versus Arm 1). Scale used ranging from 0-100. Lower scores indicate more significant limitations.
Time frame: Baseline and 6 months
Population: All participants in Arm 1 and Arms 2 and 3 combined for whom results of the SF-36 questionnaire were collected baseline and 6 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in Quality of Life Measures From Baseline | Physical Component | 2.78 score on a scale | Standard Deviation 5.11 |
| Arm 1 - Placebo During First 6 Months | Change in Quality of Life Measures From Baseline | Mental Component | -2.60 score on a scale | Standard Deviation 11.32 |
| Arm 2 and 3 During First 6 Months | Change in Quality of Life Measures From Baseline | Physical Component | 3.2 score on a scale | Standard Deviation 10.71 |
| Arm 2 and 3 During First 6 Months | Change in Quality of Life Measures From Baseline | Mental Component | -2.50 score on a scale | Standard Deviation 6.93 |
Comparison: Selection of the arms for analysis of this outcome measure is in accordance with the statistical analysis plan.p-value: 1Wilcoxon (Mann-Whitney)
Comparison: Selection of the arms for analysis of this outcome measure is in accordance with the statistical analysis plan.p-value: 0.64Wilcoxon (Mann-Whitney)
Secondary
Change in Quality of Life Measures From Baseline
Comparison in change from baseline measured by SF-36 Survey after delivery of 4 versus 8 doses of study product (Arm 2 versus Arm 3). Scale used ranging from 0-100. Lower scores indicate more significant limitations.
Time frame: 12 months
Population: All participants in Arm 2 and 3 for whom results of the SF-36 questionnaire were collected baseline and 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Change in Quality of Life Measures From Baseline | Physical Component | 10.5 Change in Score | Standard Deviation 2.78 |
| Arm 1 - Placebo During First 6 Months | Change in Quality of Life Measures From Baseline | Mental Component | 14.3 Change in Score | Standard Deviation 21.58 |
| Arm 2 and 3 During First 6 Months | Change in Quality of Life Measures From Baseline | Physical Component | 2.5 Change in Score | Standard Deviation 13.86 |
| Arm 2 and 3 During First 6 Months | Change in Quality of Life Measures From Baseline | Mental Component | -1.10 Change in Score | Standard Deviation 9.1 |
Comparison: Selection of the arms for analysis of this outcome measure is in accordance with the statistical analysis plan.p-value: 0.4Wilcoxon (Mann-Whitney)
p-value: 0.23Wilcoxon (Mann-Whitney)
Secondary
Incremental Effect of 8 Versus 4 Doses of Cell Therapy Product on PVR
Incremental effect of 8 versus 4 doses of cell therapy product on PVR at 6 and 12 months (Arm 3 only)
Time frame: 6 and12 months
Population: All participants in whom the PVR was measurement at baseline, 6, and 12 months.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 - Placebo During First 6 Months | Incremental Effect of 8 Versus 4 Doses of Cell Therapy Product on PVR | Baseline to 6 months | 0.76 Wood Units (WU) | Standard Deviation 0.87 |
| Arm 1 - Placebo During First 6 Months | Incremental Effect of 8 Versus 4 Doses of Cell Therapy Product on PVR | Baseline to 12 months | 2.15 Wood Units (WU) | Standard Deviation 3.09 |
p-value: 0.25Wilcoxon (Mann-Whitney)