Pilot Trial of Inhaled Molgramostim in Non-tuberculous Mycobacterial (NTM) Infection

NCT03421743 | Completed Phase 2 Results

• 2 other identifiers: SAV008-012017-003374-14
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 5

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 non-tuberculous mycobacterial (NTM) infection. Participants will be treated for 24-weeks with inhaled molgramostim and 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.

Conditions

Mycobacterium Infections, Nontuberculous

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Sputum Culture Conversion to Negative

  Sputum culture conversion is defined as at least 3 consecutive sputum samples without growth of NTM during the treatment period.

  48 weeks

Secondary Outcomes (18)

• Number of Participants With Sputum Smear Conversion to Negative

  48 weeks

• Number of Participants With Durable Sputum Culture Conversion

  60 weeks

• Number of Participants With Durable Sputum Smear Conversion

  60 weeks

• Change From Baseline in Symptom Scores (Assessed Using Lower Respiratory Tract Infections - Visual Analogue Scale)

  Baseline to Week 48

• Change From Baseline in Symptom Scores (Assessed Using Quality of Life Questionnaire - Bronchiectasis (QOL-B))

  Baseline to Week 48

Study Arms (2)

Inhaled molgramostim/antimycobacterials

EXPERIMENTAL

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

Drug: Inhaled molgramostim; Drug: Antimycobacterial regimen

Inhaled molgramostim

EXPERIMENTAL

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

Drug: Inhaled molgramostim

Interventions

Inhaled molgramostim DRUG

300 µg / dose molgramostim (recombinant human GM-CSF) for inhalation

Also known as: rh-GM-CSF

Inhaled molgramostim; Inhaled molgramostim/antimycobacterials

Antimycobacterial regimen DRUG

Multidrug NTM guideline-based antimycobacterial regimen

Inhaled molgramostim/antimycobacterials

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.
• 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.
• Female or male ≥18 years of age.
• 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.
• 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.
• Willing and able to provide signed informed consent.
• 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

You may not qualify if:

• Subjects diagnosed with cystic fibrosis.
• Prior therapy with inhaled or systemic GM-CSF.
• Subjects with hemoptysis of ≥60 mL in a 24 hour period within 4 weeks prior to Screening.
• Concurrent disease with a life expectancy of less than 6 months.
• History of, or present, myeloproliferative disease, leukemia or other hematological malignancy.
• 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.
• 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.
• Pulmonary tuberculosis requiring treatment or treated within 2 years prior to Screening.
• HIV infection or other disease associated with significant immunodeficiency.
• History of lung transplantation.
• Any change in chronic NTM multi-drug antimycobacterial regimen within 28 days prior to Screening.
• Treatment with any investigational medicinal product within 3 months of Screening.
• Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
• Any other serious medical condition which in the opinion of the investigator would make the subject unsuitable for the trial.

Sponsors & Collaborators

• Savara Inc.: lead

Study Sites (5)

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

The Prince Charles Hospital

Chermside West, Queensland, 4032, Australia

Location

Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6000, Australia

Location

Royal Brompton Hospital

London, SW3 6NP, United Kingdom

Location

Related Publications (1)

• Thomson RM, Loebinger MR, Burke AJ, Morgan LC, Waterer GW, Ganslandt C. OPTIMA: An Open-Label, Noncomparative Pilot Trial of Inhaled Molgramostim in Pulmonary Nontuberculous Mycobacterial Infection. Ann Am Thorac Soc. 2024 Apr;21(4):568-576. doi: 10.1513/AnnalsATS.202306-532OC.

  PMID: 37948736 DERIVED

MeSH Terms

Conditions

Mycobacterium Infections, Nontuberculous

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Limitations and Caveats

This was an exploratory study without hypothesis testing. Only descriptive statistics were used. The study included participants with treatment refractory NTM infection, who were severely affected by their background disease (in most cases bronchiectasis). These participants probably had an even lower potential for improvement than was assumed prior to the study. The study was further limited by the lack of a placebo control.

Results Point of Contact

• Title: Paymond D Pratt, Chief Medical Officer
• Organization: Savara Inc

ray.pratt@savarapharma.com

+1 512 784 8757

Study Officials

• Grant Waterer, Prof.

  Royal Perth Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, non-controlled, multicenter, pilot clinical trial

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: February 5, 2018
• Study Start: March 1, 2018
• Primary Completion: October 15, 2019
• Study Completion: January 13, 2020
• Last Updated: July 3, 2024
• Results First Posted: July 3, 2024

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4); GB (1)