Human MesenchymAl Stem Cells Infusion in Patients With Cystic Fibrosis

NCT03058068 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 20160140
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Incidence of any treatment-emergent serious adverse event (TE-SAE)

  Incidence of any treatment-emergent serious adverse event (TE-SAE), defined as one or more of the following untoward medical occurrences happening within the first 30 days after infusion.

  30 days after infusion

Secondary Outcomes (11)

• Change in Symptoms for pulmonary function test

  baseline to 12 months

• Change in Symptoms 6-minute walk test

  baseline to 12 months

• Change in Symptoms of body mass index

  baseline to 12 months

• Change in Rate of pulmonary exacerbations

  baseline to 12 months

• Change in Local and Systemic Inflammation in inflammatory markers

  baseline to 12 months

Study Arms (5)

Safety Run-In: Treatment 1 Allo-hMSCs

EXPERIMENTAL

Treatment 1: 1 subject will receive a single administration of allogeneic MSCs: 20 x 10\^6 MSCs (20 million) cells delivered via peripheral intravenous infusion.

Biological: Allo-hMSCs

Safety Run-In: Treatment 2 Allo-hMSCs

EXPERIMENTAL

2 subjects will receive a single administration of allogeneic MSCs: 100 x 10\^6 MSCs (100 million) cells delivered via peripheral intravenous infusion.

Biological: Allo-hMSCs

Randomized: Cohort 1 Allo-hMSCs

EXPERIMENTAL

Cohort 1 (5 subjects): 20 million MSCs A single peripheral intravenous infusion of 20 x 10\^6 MSCs (20 million cells) will be administered to each subject.

Biological: Allo-hMSCs

Randomized: Cohort 2 Allo-hMSCs

EXPERIMENTAL

Cohort 2 (5 subjects): 100 million MSCs A single peripheral intravenous infusion of 100 x 10\^6 MSCs (100 million cells) will be administered to each subject.

Biological: Allo-hMSCs

Randomized: Cohort 3 Allo-hMSCs

PLACEBO COMPARATOR

Cohort 3 (5 subjects): Placebo A single peripheral intravenous infusion of placebo (PlasmaLyte A containing 1% HSA) will be administered to each subject.

Biological: Placebo

Interventions

Allo-hMSCs BIOLOGICAL

1 peripheral intravenous infusion of allogeneic human mesenchymal stem cells (hMSCs)

Also known as: Stem cells

Randomized: Cohort 1 Allo-hMSCs; Randomized: Cohort 2 Allo-hMSCs; Safety Run-In: Treatment 1 Allo-hMSCs; Safety Run-In: Treatment 2 Allo-hMSCs

Placebo BIOLOGICAL

1 peripheral intravenous infusion

Randomized: Cohort 3 Allo-hMSCs

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Joshua M Hare: lead

Related Links

• Interdisciplinary stem cell institute (ISCI) at the University of Miami

MeSH Terms

Conditions

Cystic Fibrosis

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Matthias A Salathe, MD

  ISCI / University of Miami / Division of Pulmonary

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Masking will apply to the randomized phase.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor

Model Details: 1. Safety run-in phase will have 3 subjects with 2 treatment groups 2. Randomized phase will have 15 subjects with 3 treatment groups

Study Record Dates

• First Submitted: February 6, 2017
• First Posted: February 20, 2017
• Study Start: December 1, 2020
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: May 13, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share