Human MesenchymAl Stem Cells Infusion in Patients With Cystic Fibrosis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03058068
• Date of registration: 06/02/2017
• Prospective Registration: Yes
• Primary sponsor: Joshua M Hare
• Public title: Human MesenchymAl Stem Cells Infusion in Patients With Cystic Fibrosis HAPI
• Scientific title: 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
• Date of first enrolment: December 2020
• Target sample size: 0
• Recruitment status: Withdrawn
• URL: https://clinicaltrials.gov/show/NCT03058068
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Matthias A Salathe, MD
• Affiliation: ISCI / University of Miami / Division of Pulmonary

Key inclusion & exclusion criteria

Inclusion Criteria:

- Provide written informed consent.

- Be 20 - 45 years of age at the time of signing the Informed Consent Form.

- Have a confirmed diagnosis of cystic fibrosis as defined by two or more clinical
features of cystic fibrosis (CF), including by the 1997 CF

Consensus criteria (NIH Consensus Statement, 1997):

One or more accompanying clinical features consistent with Cystic fibrosis, and at least
one of the following:

1. Documented sweat chloride test = 60 mEq/L by quantitative pilocarpine iontophoresis
or,

2. Abnormal nasal transepithelial potential difference (NPD) test or,

3. 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
(ß-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:

- Inhaled medications (bronchodilators, steroids, pulmozyme, hypertonic saline
and inhaled antibiotics to suppress chronic infections including tobramycin,
amikacin, colistin, aztreonam lysine)

- Chronic azithromycin use (three times weekly)

- Vitamin supplementation

- Pancreatic enzymes

- CFTR potentiator and/or corrector (ivacaftor and lumacaftor)

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:

- hemoglobin <12.1 g/dL (females) or <13.6 g/dL (males).

- white blood cell count < 3000/mm3.

- platelets < 150,000/mm3.

- International normalized ratio (INR) ? 1.5 not due to a reversible cause (i.e.
Coumadin).

- aspartate transaminase, alanine transaminase, or alkaline phosphatase ? 2 times
upper limit of normal.

- 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.



Age minimum: 20 Years
Age maximum: 45 Years
Gender: All

Health Condition(s) or Problem(s) studied

Cystic Fibrosis

Intervention(s)

Biological: Placebo

Biological: Allo-hMSCs

Primary Outcome(s)

Incidence of any treatment-emergent serious adverse event (TE-SAE) [Time Frame: 30 days after infusion]

Secondary Outcome(s)

Change in Local and Systemic Inflammation in inflammatory markers [Time Frame: baseline to 12 months]

Change in Local and Systemic Inflammation via the CFQ-R Questionnaire [Time Frame: baseline to 12 months]

Change in Rate of pulmonary exacerbations [Time Frame: baseline to 12 months]

Change in Local and Systemic Inflammation related to quality of life [Time Frame: baseline to 12 months]

Change in Local and Systemic Inflammation via the short form-36 [Time Frame: baseline to 12 months]

Change in Local and Systemic Inflammation for sputum inflammatory markers [Time Frame: baseline to 12 months]

Change in Symptoms of body mass index [Time Frame: baseline to 12 months]

Change in Local and Systemic Inflammation via the GAD-7 Questionnaire [Time Frame: baseline to 12 months]

Change in Symptoms 6-minute walk test [Time Frame: baseline to 12 months]

Change in Local and Systemic Inflammation via the PHQ-9 Questionnaire [Time Frame: baseline to 12 months]

Change in Symptoms for pulmonary function test [Time Frame: baseline to 12 months]

Secondary ID(s)

20160140

Source(s) of Monetary Support

Please refer to primary and secondary sponsors