| Eligibility |
Inclusion Criteria:
1. Written informed consent obtained from participant.
2. Confirmed diagnosis of CF according to the Cystic Fibrosis Foundation (CFF) 2017
Consensus Guidelines.
3. History of chronic pulmonary infection with M. avium complex (MAC) or M. abscessus
complex (MABSC) (defined as at least three positive NTM cultures (sputum or BAL for
the same species (MAC) or subspecies (MABSC) within the 2 years prior to the screening
visit, with at least one positive within the past 6 months and a minimum of 50% of NTM
cultures positive over the past 2 years) that does not demonstrate response to current
treatment course based on decreasing NTM burden or frequency of positive cultures, and
in the opinion of the Investigator is unlikely to resolve with current treatment
course.
4. Subject fulfills criteria for inclusion in one of the following groups:
Group 1: Subject with chronic pulmonary MAC or MABSC infection currently on a
multidrug NTM guideline-based antimycobacterial regimen, which has been ongoing for at
least 9 months prior to the Baseline visit.
Group 2: Subject with chronic pulmonary MAC or MABSC infection who has stopped a
multidrug NTM guideline-based antimycobacterial regimen at least 28 days prior to
Screening due to lack of response or intolerance.
Group 3: Subjects with chronic pulmonary MAC or MABSC infection not meeting
recommendations for treatment with a multidrug NTM guideline-based antimycobacterial
regimen based on failure to meet ATS/IDSA criteria for NTM pulmonary disease (i.e.
absence of radiologic findings and clinical symptoms beyond what is expected from
underlying CF).
5. Ability to produce sputum or be willing to undergo an induction protocol that produces
sputum for clinical evaluation.
6. An additional sputum culture performed by the central laboratory, which is positive
for the same species (MAC) or subspecies (MABSC) of NTM as before the trial within 10
weeks of Baseline.
7. CF which in the Investigator's opinion is clinically stable and not expected to
require lung transplantation within the next year.
8. FEV1 = 30% of predicted at screening that is normalized for age, gender, race, and
height, using the Global Lung Function Initiative (GLI) equation.
9. Subjects who are co-infected with a respiratory pathogen, e.g. P. aeruginosa or S.
aureus, must either be stable on a regular suppression antibiotic regimen or must be,
in the opinion of the Investigator, stable despite the lack of such treatment.
10. Female or male =18 years of age.
11. If female, subjects who have been post-menopausal for more than 1 year or females of
childbearing potential after a confirmed menstrual period using a highly efficient
method of contraception (i.e. a method with less than 1% failure rate) during and
until 30 days after last dose of trial treatment, having a negative serum pregnancy
test at Screening (Visit 1) and a negative urine pregnancy test at dosing at Baseline
(Visit 2) and must not be lactating.
For purposes of this study, the Sponsor defines "acceptable methods of contraception"
as:
- Oral birth control pills administered for at least 1 monthly cycle prior to
administration of the study drug.
- A synthetic progestin implanted rod (eg, Implanon®) for at least 1 monthly cycle
prior to the study drug administration but not beyond the 4th successive year
following insertion.
- Intrauterine devices (IUDs), inserted by a qualified clinician for at least 1
monthly cycle prior to study drug administration.
- Medroxyprogesterone acetate (eg, Depo-Provera®) administered for a minimum of 1
monthly cycle prior to administration of the study drug and continuing through 1
month following study completion.
- Hysterectomy or surgical sterilization.
- Vasectomized partner
- Abstinence.
Double barrier method (diaphragm with spermicidal gel or condoms with contraceptive
foam) is not considered an acceptable form of contraception.
NOTE: For subjects prescribed Orkambi: Orkambi may substantially decrease hormonal
contraceptive exposure, reducing the effectiveness and increasing the incidence of
menstruation-associated adverse reactions. Hormonal contraceptives, including oral,
injectable, transdermal, and implantable, should not be relied upon as an effective
method of contraception when co-administered with Orkambi.
12. If male, subjects who, if sexually active of reproductive potential and non-sterile
(i.e., male who has not been sterilized by vasectomy for at least 6 months and not
diagnosed with infertility through demonstration of azoospermia in a semen sample
and/or absence of vas deferens through ultrasound) are willing to use a barrier method
of contraception, or their female partner must use an acceptable method of
contraception, during the study and until 30 days after last dose of medication.
13. Willing and able to comply with scheduled visits, treatment plan, laboratory tests,
and other trial procedures specified in the protocol as judged by the Investigator.
Exclusion criteria:
1. Use of non-maintenance antibiotic for a concurrent pulmonary or extrapulmonary
infection within 28 days prior to the Baseline visit.
2. Use of a maintenance antibiotic regimen containing azithromycin for a concurrent
non-NTM pulmonary infection within 28 days prior to the Baseline visit. For subjects
in Group 1, azithromycin is allowed if part of ongoing multidrug NTM guideline-based
antimycobacterial regimen.
3. Prior therapy with inhaled or systemic granulocyte macrophage colony stimulating
factor (GM-CSF).
4. Subjects with hemoptysis of =60 mL in a 24-hour period within 4 weeks prior to
Screening.
5. Life expectancy of less than 6 months according to Investigator's judgement.
6. History of, or present, myeloproliferative disease, leukemia or other hematological
malignancy.
7. Active pulmonary malignancy (primary or metastatic); or any malignancy requiring
chemotherapy or radiation therapy within 1 year prior to Screening or anticipated
during the study period.
8. Active autoimmune disorder or other condition requiring therapy associated with
significant immunosuppression, e.g. such as systemic corticosteroids at a dose
equivalent of 10 mg/day or more of prednisolone or other significant immunosuppressant
medications, within 3 months prior to Screening or anticipated during the study
period. Inhaled or topical corticosteroids, or brief courses (<14 days) of systemic
corticosteroids for pulmonary exacerbations or other self-limited conditions are
permitted.
9. Changes in antimicrobial, bronchodilator, anti-inflammatory or corticosteroid
medications, or changes in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)
modulators, within 28 days prior to the Baseline visit.
10. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to
Screening.
11. History of human immunodeficiency virus (HIV) infection or other disease associated
with significant immunodeficiency.
12. History of lung or other solid organ transplantation or currently on the list to
receive lung or other solid organ transplantation.
13. History of congestive heart failure (CHF) New York Heart Association (NYHA) Class III
or greater in severity.
14. History of cardiovascular ischemic event within 6 months of Baseline.
15. Any change in chronic NTM multi-drug antimycobacterial regimen within 28 days prior to
Screening.
16. Treatment with any investigational medicinal product within 28 days of Screening.
17. Previous experience of severe and unexplained side-effects during aerosol delivery of
any kind of medicinal product.
18. Any other condition that, in the opinion of the Investigator, would preclude informed
consent or assent, make study participation unsafe, complicate interpretation of study
outcome data, or otherwise interfere with achieving the study objectives.
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