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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03421743




Registration number
NCT03421743
Ethics application status
Date submitted
16/01/2018
Date registered
29/01/2018
Date last updated
26/11/2018

Titles & IDs
Public title
Pilot Trial of Inhaled Molgramostim in Nontuberculous Mycobacterial (NTM) Infection
Scientific title
An Open-label, Non-controlled, Multicentre, Pilot Clinical Trial of Inhaled Molgramostim in Subjects With Antibiotic-resistant Non-tuberculosis Mycobacterial (NTM) Infection
Secondary ID [1] 0 0
SAV-008-01
Universal Trial Number (UTN)
Trial acronym
OPTIMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mycobacterium Infections, Nontuberculous 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Inhaled molgramostim

Experimental: Inhaled molgramostim/antimycobacterials - Inhaled molgramostim administered in subjects who remain sputum culture positive while currently on a multidrug Nontuberculous Mycobacterial (NTM) guideline based antimycobacterial regimen, which has been ongoing for at least 6 months prior to the Baseline Visit

Experimental: Inhaled molgramostim - Inhaled molgramostim administered in subjects who remain sputum culture positive but have stopped a multidrug Nontuberculous Mycobacterial (NTM) guideline based antimycobacterial regimen at least 28 days prior to Screening due to lack of response or intolerance, or who never started such treatment


Treatment: Drugs: Inhaled molgramostim
300 µg / dose molgramostim (recombinant human GM-CSF) for inhalation

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects with sputum culture conversion to negative - Sputum culture conversion is defined as at least three consecutive sputum samples without growth of Nontuberculous Mycobacteria (NTM) during the treatment period.
Timepoint [1] 0 0
24 weeks
Secondary outcome [1] 0 0
Number of subjects with sputum smear conversion to negative - Sputum smear conversion is defined as at least three consecutive negative acid-fast bacilli (AFB) stained sputum smears on microscopy during the treatment period among subjects who were smear positive at Baseline.
Timepoint [1] 0 0
24 weeks
Secondary outcome [2] 0 0
Number of subjects with durable sputum culture conversion - Durability is defined as sputum culture conversion at or before Week 24 and culture still negative for growth of NTM at 12-weeks follow-up.
Timepoint [2] 0 0
36 weeks
Secondary outcome [3] 0 0
Number of subjects with durable sputum smear conversion - Durability is defined as sputum smear conversion at or before Week 24 and AFB stained smear still negative for NTM at 12-weeks follow-up among subjects who were smear positive at Baseline.
Timepoint [3] 0 0
36 weeks
Secondary outcome [4] 0 0
Change in semi-quantitative grade of number of NTM on microscopy of AFB stained sputum smears
Timepoint [4] 0 0
36 weeks
Secondary outcome [5] 0 0
Change in semi-quantitative grade of sputum cultures
Timepoint [5] 0 0
36 weeks
Secondary outcome [6] 0 0
Change in symptom scores (assessed using Lower Respiratory Tract Infections - Visual Analogue Scale (LRTI-VAS)
Timepoint [6] 0 0
36 weeks
Secondary outcome [7] 0 0
Change in Quality of Life scores (assessed using Quality of Life Questionnaire - Bronchiectasis (QOL-B))
Timepoint [7] 0 0
36 weeks
Secondary outcome [8] 0 0
Change in Global Rating of Health (GRH)
Timepoint [8] 0 0
36 weeks
Secondary outcome [9] 0 0
Change in body weight
Timepoint [9] 0 0
36 weeks
Secondary outcome [10] 0 0
Change in 6-minute walk distance (6MWD)
Timepoint [10] 0 0
36 weeks
Secondary outcome [11] 0 0
Change in oxygen desaturation during a 6-minute walk test (6MWT)
Timepoint [11] 0 0
36 weeks
Secondary outcome [12] 0 0
Change in Borg CR10 scores for dyspnea during a 6MWT
Timepoint [12] 0 0
36 weeks
Secondary outcome [13] 0 0
Number of adverse events (AEs) during the trial period
Timepoint [13] 0 0
36 weeks
Secondary outcome [14] 0 0
Number of serious AEs (SAEs) during the trial period
Timepoint [14] 0 0
36 weeks
Secondary outcome [15] 0 0
Number of adverse drug reactions (ADRs) during the trial period
Timepoint [15] 0 0
36 weeks
Secondary outcome [16] 0 0
Number of severe AEs during the trial period
Timepoint [16] 0 0
36 weeks
Secondary outcome [17] 0 0
Number of AEs leading to treatment discontinuation during the trial period
Timepoint [17] 0 0
36 weeks
Secondary outcome [18] 0 0
Change in white blood cell counts (WBC) in blood
Timepoint [18] 0 0
36 weeks
Secondary outcome [19] 0 0
Change in white cell differential counts in blood
Timepoint [19] 0 0
36 weeks
Secondary outcome [20] 0 0
Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Timepoint [20] 0 0
24 weeks
Secondary outcome [21] 0 0
Change in forced expiratory volume in 1 second (FEV1) (% predicted)
Timepoint [21] 0 0
24 weeks
Secondary outcome [22] 0 0
Change in forced vital capacity (FVC) (% predicted)
Timepoint [22] 0 0
24 weeks
Secondary outcome [23] 0 0
Number of subjects with development of anti-molgramostim antibodies in serum
Timepoint [23] 0 0
36 weeks

Eligibility
Key inclusion criteria
1. History of chronic pulmonary infection with MAC or M. abscessus (defined as at least 2
documented positive sputum cultures in the prior 2 years, of which at least one was
obtained in the 6 months prior to Screening).

2. Subject fulfills one of the following criteria:

- Subjects who remain sputum culture positive while currently on a multidrug NTM
guideline based antimycobacterial regimen, which has been ongoing for at least 6
months prior to the Baseline Visit

- Subjects who remain sputum culture positive but have either stopped a multidrug
NTM guideline based antimycobacterial regimen at least 28 days prior to Screening
due to lack of response or intolerance, or never started such treatment.

3. Ability to produce at least 2 mL of sputum or be willing to undergo an induction that
produces at least 2 mL of sputum for clinical evaluation.

4. Female or male =18 years of age.

5. Females 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 such as combined hormonal
contraception, progesterone-only hormonal contraception, intrauterine device,
intrauterine hormone- releasing system, bilateral tubal occlusion, vasectomized
partner, sexual abstinence), during and until thirty (30) days after last dose of
trial treatment. Females of childbearing potential must have 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.

6. Males agreeing to use condoms during and until thirty (30) days after last dose of
medication, or males having a female partner who is using adequate contraception as
described above.

7. Willing and able to provide signed informed consent.

8. 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects diagnosed with cystic fibrosis.

2. Prior therapy with inhaled or systemic GM-CSF.

3. Subjects with hemoptysis of =60 mL in a 24 hour period within 4 weeks prior to
Screening.

4. Concurrent disease with a life expectancy of less than 6 months.

5. History of, or present, myeloproliferative disease, leukemia or other hematological
malignancy.

6. Active pulmonary malignancy (primary or metastatic); or any malignancy requiring
chemotherapy or radiation therapy within one year prior to Screening or anticipated
during the study period.

7. Active allergic bronchopulmonary mycosis or connective tissue disease, inflammatory
bowel disease or other autoimmune disorder requiring therapy associated with
significant immunosuppression, such as systemic corticosteroids at a dose equivalent
of 10 mg/day or more of prednisolone, within 3 months prior to Screening or
anticipated during the study period.

8. Pulmonary tuberculosis requiring treatment or treated within 2 years prior to
Screening.

9. HIV infection or other disease associated with significant immunodeficiency.

10. History of lung transplantation.

11. Any change in chronic NTM multi-drug antimycobacterial regimen within 28 days prior to
Screening.

12. Treatment with any investigational medicinal product within 3 months of Screening.

13. Previous experience of severe and unexplained side-effects during aerosol delivery of
any kind of medicinal product

14. Any other serious medical condition which in the opinion of the investigator would
make the subject unsuitable for the trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [2] 0 0
The Prince Charles Hospital - Chermside West
Recruitment hospital [3] 0 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
4032 - Chermside West
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United Kingdom
State/province [1] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Savara Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The trial is an open-label, non-controlled, multicenter, pilot clinical trial of inhaled
molgramostim (recombinant human Granulocyte-Macrophage Colony Stimulating Factor; rhGM-CSF)
in subjects with persistent pulmonary Nontuberculous Mycobacterial (NTM) infection. Subject
will be treated for 24-weeks with inhaled molgramostim and will be followed up for 12-weeks
after end of treatment. The primary aim of the trial is to investigate the efficacy of
inhaled molgramostim on NTM sputum culture conversion to negative.
Trial website
https://clinicaltrials.gov/show/NCT03421743
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Grant Waterer, Prof.
Address 0 0
Royal Perth Hospital
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No data has been provided for results reporting
Summary results
Other publications