A Phase I, Randomized and Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Potential Efficacy of Allogeneic Human MesenchymAl Stem Cells Infusion in Patients With Cystic Fibrosis - HAPI
A Phase I, Randomized and Placebo-controlled Trial to Evaluate the Safety, Tolerability, and Potential Efficacy of Allogeneic Human MesenchymAl Stem Cells Infusion in Patients With Cystic Fibrosis - HAPI
A Safety Run-In will be followed by a Double-Blinded Randomized Phase. All subjects shall meet the inclusion/exclusion criteria, and will be evaluated prior to the scheduled infusion to establish baseline.
There will be 3 subjects in the safety run-in phase and 15 subjects in the double-blinded phase.
Primary objective is to demonstrate the safety of Mesenchymal Stem Cells (MSCs) intravenously administered to subjects with cystic fibrosis.
Secondary Objective is to explore if MSCs can improve the symptoms of cystic fibrosis, including lung function, the rate of pulmonary exacerbation, systemic and local inflammation and symptom-related quality of life.
The Safety Run-In will be performed to evaluate the safety of MSC infusion into subjects with cystic fibrosis. 3 subjects will participate and they will receive a single administration of allogeneic MSCs given through intravenous infusion.
In the randomized phase the subjects will be randomized at a ratio of 1:1:1 into 3 cohorts to receive infusions. There will be a total of 15 subjects in 3 cohorts.
The total duration for each subject after infusion is 12 months, plus up to an additional 2 months for the Screening and Baseline Visits. Approximately 9 visits in total.
Inclusion Criteria:
Consensus criteria (NIH Consensus Statement, 1997):
One or more accompanying clinical features consistent with Cystic fibrosis, and at least one of the following:
Documented sweat chloride test ≥ 60 mEq/L by quantitative pilocarpine iontophoresis or,
Abnormal nasal transepithelial potential difference (NPD) test or,
Two well-characterized, disease-causing genetic mutations in the CF transmembrane conductance regulator (CFTR) gene on different alleles
FEV1 at screening visit between 25% and 80% of predicted values for age, sex, and height taken 4 hours or more after last dose of short-acting bronchodilators (β-agonists and/or anticholinergics). The predicted values will be calculated according to National Health and Nutrition Examination Survey (NHANES).
Total bilirubin below 1.9 mg/dL.
Non-smoker for the past 60 days (2 months) prior to screening Visit 1 and less than a 5 pack-year lifetime history of smoking
Stable regimen of CF medications and chest physiotherapy for the 28 days prior to screening, and no anticipated need for changes during the study period for the immediate future, at least 4 weeks post infusion.
Clinically stable for at least 4 weeks with no evidence of new or acute respiratory symptoms, excluding symptoms of allergic (perennial or seasonal) or non-allergic rhinitis.
Patients should be on a stable medication regimen as determined by their Cystic fibrosis physician. Allowable medications include:
Exclusion Criteria:
All subjects enrolled in this trial must not:
Be unable to perform any of the assessments required for endpoint analysis.
Use systemic corticosteroids (≥5 mg of prednisone per day).
Have been on intravenous or oral antibiotics within the last 4 weeks
Have a clinical history of malignancy within 5 years (i.e., subjects with prior malignancy must be disease free for 5 years), except curatively- treated basal cell carcinoma, squamous cell carcinoma, melanoma in situ or cervical carcinoma, if recurrence occurs.
Have congestive heart failure (NYHA Class III or IV).
Have severe pulmonary hypertension with a right ventricle systolic pressure (RVSP) >50 mmHg as estimated by echocardiography
Have chronic kidney disease Stage 4 or 5.
Have a non-pulmonary condition that limits lifespan to ≤1 year.
Have clinically significant autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus (SLE), or inflammatory bowel disease).
Have HIV, AIDS, or other immunodeficiency.
Test positive for hepatitis B HsAg, viremic hepatitis C, HIV1, HIV2, HTLV-I, HTLV-II, syphilis, and West Nile Virus.
Have a resting blood oxygen saturation of <93% (measured by pulse oximetry).
Have documented current substance and/or alcohol abuse.
Be a current user of tobacco products.
Have a known hypersensitivity to dimethyl sulfoxide (DMSO).
Have had a recent (within prior 3 months) trauma or surgery.
Be an organ transplant recipient.
Be actively listed (or expected to be listed) for transplant of any organ other than for a lung transplant.
Have any clinically important abnormal screening laboratory values, including but not limited to:
Have a sitting or resting systolic blood pressure >180 mm Hg or diastolic blood pressure >110 mm Hg at Screening.
Have any serious comorbid illness or any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study, or that may compromise the validity of the study.
Be a female who is pregnant, nursing, or of childbearing potential while not practicing effective contraception (female patients must undergo a blood or urine pregnancy test at screening and prior to infusion). Females who are in childbearing age must agree to practice a highly effective form of contraception throughout the study. Highly effective forms of contraception with a low failure rate include barrier methods, oral contraception or depot contraceptives (unless on Orkambi), an intrauterine device, implantable devices.
Be currently participating in an investigational therapeutic or device trial, or have participated in an investigational therapeutic or device trial within the previous 30 days, or participate in any other clinical trial for the duration of the time that the subject actively participates in this trial.