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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03421743
Ethics application status
Date submitted
16/01/2018
Date registered
5/02/2018

Titles & IDs
Public title
Pilot Trial of Inhaled Molgramostim in Non-tuberculous 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
2017-003374-14
Secondary ID [2] 0 0
SAV008-01
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
Treatment: Drugs - Antimycobacterial regimen

Experimental: Inhaled molgramostim/antimycobacterials - Inhaled molgramostim administered in participants 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

Experimental: Inhaled molgramostim - Inhaled molgramostim administered in participants who remain sputum culture positive but have stopped a multidrug 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

Treatment: Drugs: Antimycobacterial regimen
Multidrug NTM guideline-based antimycobacterial regimen

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

Outcomes
Primary outcome [1] 0 0
Number of Participants With Sputum Culture Conversion to Negative
Timepoint [1] 0 0
48 weeks
Secondary outcome [1] 0 0
Number of Participants With Sputum Smear Conversion to Negative
Timepoint [1] 0 0
48 weeks
Secondary outcome [2] 0 0
Number of Participants With Durable Sputum Culture Conversion
Timepoint [2] 0 0
60 weeks
Secondary outcome [3] 0 0
Number of Participants With Durable Sputum Smear Conversion
Timepoint [3] 0 0
60 weeks
Secondary outcome [4] 0 0
Change From Baseline in Symptom Scores (Assessed Using Lower Respiratory Tract Infections - Visual Analogue Scale)
Timepoint [4] 0 0
Baseline to Week 48
Secondary outcome [5] 0 0
Change From Baseline in Symptom Scores (Assessed Using Quality of Life Questionnaire - Bronchiectasis (QOL-B))
Timepoint [5] 0 0
Baseline to Week 48
Secondary outcome [6] 0 0
Change From Baseline in Global Rating of Health (GRH)
Timepoint [6] 0 0
Baseline to Week 48
Secondary outcome [7] 0 0
Change From Baseline in Body Weight
Timepoint [7] 0 0
Baseline to Week 48
Secondary outcome [8] 0 0
Change From Baseline in 6-Minute Walking Distance (6MWD)
Timepoint [8] 0 0
Baseline to Week 48
Secondary outcome [9] 0 0
Change From Baseline in Dyspnea Scores During a 6MWT
Timepoint [9] 0 0
Baseline to Week 48
Secondary outcome [10] 0 0
Number of Adverse Events (AEs) During the Trial Period
Timepoint [10] 0 0
60 weeks
Secondary outcome [11] 0 0
Number of Serious AEs (SAEs) During the Trial Period
Timepoint [11] 0 0
60 weeks
Secondary outcome [12] 0 0
Number of Adverse Drug Reactions (ADRs) During the Trial Period
Timepoint [12] 0 0
60 weeks
Secondary outcome [13] 0 0
Number of Severe AEs During the Trial Period
Timepoint [13] 0 0
60 weeks
Secondary outcome [14] 0 0
Number of Participants Withdrawn From Treatment Due to an AE During the Trial Period
Timepoint [14] 0 0
60 weeks
Secondary outcome [15] 0 0
Change From Baseline in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Timepoint [15] 0 0
Baseline to Week 48
Secondary outcome [16] 0 0
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) (% Predicted)
Timepoint [16] 0 0
Baseline to Week 48
Secondary outcome [17] 0 0
Change From Baseline in Forced Vital Capacity (FVC) (% Predicted)
Timepoint [17] 0 0
Baseline to Week 48
Secondary outcome [18] 0 0
Number of Subjects With Development of Anti-GM-CSF Antibodies in Serum
Timepoint [18] 0 0
60 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
Sex
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
Completed
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
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.