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Cystic FibrosisPhase 1HAPINCT03058068

Human MesenchymAl Stem Cells Infusion in Patients With Cystic Fibrosis

A Phase 1 study testing Allo-hMSCs in people with Cystic Fibrosis, run by Joshua M Hare.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 20 to 45 years
Conditions the study is for
Cystic Fibrosis
What is being tested?
Allo-hMSCs
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Dec 2020to Sep 2028
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 to 45 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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,
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  • 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)
  • Chronic azithromycin use (three times weekly)
  • Vitamin supplementation
  • Pancreatic enzymes
  • CFTR potentiator and/or corrector (ivacaftor and lumacaftor)

Who cannot join

  • 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).
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  • 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.

About this study

Official 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

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.

Read the detailed description

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.

Conditions
Cystic Fibrosis
Being tested
Allo-hMSCs, Placebo
Medical subject headings
Cystic Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Allo-hMSCsBiological

    Also called Stem cells

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

  • PlaceboBiological

    1 peripheral intravenous infusion

Study groups in NCT03058068
Study groupRoleWhat they receive
Safety Run-In: Treatment 1 Allo-hMSCsExperimentalTreatment 1: 1 subject will receive a single administration of allogeneic MSCs: 20 x 10^6 MSCs (20 million) cells delivered via peripheral intravenous infusion.
Receives: Biological: Allo-hMSCs
Safety Run-In: Treatment 2 Allo-hMSCsExperimental2 subjects will receive a single administration of allogeneic MSCs: 100 x 10^6 MSCs (100 million) cells delivered via peripheral intravenous infusion.
Receives: Biological: Allo-hMSCs
Randomized: Cohort 1 Allo-hMSCsExperimentalCohort 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.
Receives: Biological: Allo-hMSCs
Randomized: Cohort 2 Allo-hMSCsExperimentalCohort 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.
Receives: Biological: Allo-hMSCs
Randomized: Cohort 3 Allo-hMSCsPlacebo comparatorCohort 3 (5 subjects): Placebo A single peripheral intravenous infusion of placebo (PlasmaLyte A containing 1% HSA) will be administered to each subject.
Receives: Biological: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 30 days after infusion

Secondary outcomes (11)

  1. Change in Symptoms for pulmonary function test

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Resting pulmonary function tests (PFTs) assessed via spirometry: forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1 to FVC ratio, and forced expiratory flow between 25 - 75% of VC (FEF25-75) measured in adherence to American Thoracic Society/European Respiratory Society guidelines.

    Measured: baseline to 12 months

  2. Change in Symptoms 6-minute walk test

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • 6-minute walk test (6MWT).

    Measured: baseline to 12 months

  3. Change in Symptoms of body mass index

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Changes in body mass index

    Measured: baseline to 12 months

  4. Change in Rate of pulmonary exacerbations

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Incidence of investigator-defined pulmonary exacerbation: events meeting the modified Fuchs' criteria (at least 4 of 12 signs and symptoms with or without intravenous or oral antibiotic treatment).
    • Semi-quantitative sputum cultures (change in colony forming units)
    • Procalcitonin serum levels

    Measured: baseline to 12 months

  5. Change in Local and Systemic Inflammation in inflammatory markers

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Serum Inflammatory markers (CBC with differential, TNFα, C-reactive protein, Interleukin-1, Interleukin-6, D-dimer, Fibrinogen).

    Measured: baseline to 12 months

  6. Change in Local and Systemic Inflammation for sputum inflammatory markers

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Sputum inflammatory markers

    Measured: baseline to 12 months

  7. Change in Local and Systemic Inflammation related to quality of life

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Symptom Related Quality of Life

    Measured: baseline to 12 months

  8. Change in Local and Systemic Inflammation via the short form-36

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of:

    • Physical activity via the short form-36 questionnaires.

    Measured: baseline to 12 months

  9. Change in Local and Systemic Inflammation via the PHQ-9 Questionnaire

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of: • Subject quality of life (QOL) assessments via:

    • Patient Health Questionnaire-9 (PHQ-9) for depression screening

    Measured: baseline to 12 months

  10. Change in Local and Systemic Inflammation via the CFQ-R Questionnaire

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of: • Subject quality of life (QOL) assessments via:

    • Cystic Fibrosis Questionnaire-Revised (CFQ-R)

    Measured: baseline to 12 months

  11. Change in Local and Systemic Inflammation via the GAD-7 Questionnaire

    examining post-infusion changes from baseline between the MSC and Placebo Cohorts in terms of: • Subject quality of life (QOL) assessments via:

    • Generalized anxiety disorder 7 (GAD-7)

    Measured: baseline to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2017
  2. Study startDec 2020 (estimated)
  3. Primary completionSep 2027 (estimated)
  4. Study completionSep 2028 (estimated)

Why it stopped: PI left the institution

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
1. Safety run-in phase will have 3 subjects with 2 treatment groups 2. Randomized phase will have 15 subjects with 3 treatment groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03058068
Sponsor's protocol ID
20160140
Acronym
HAPI
Status last verified
May 2020
First submitted
6 Feb 2017
Last updated
13 May 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Allo-hMSCs in people with Cystic Fibrosis, run by Joshua M Hare.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 May 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of any treatment-emergent serious adverse event (TE-SAE) (time frame: 30 days after infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03058068.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2020.

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