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

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ClinicalTrials.gov Identifier: NCT03421743
Recruitment Status : Not yet recruiting
First Posted : February 5, 2018
Last Update Posted : February 5, 2018
Sponsor:
Information provided by (Responsible Party):
Savara Inc.

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-Tuberculosis 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.

Condition or disease Intervention/treatment Phase
Mycobacterium Infections, Nontuberculous Drug: Inhaled molgramostim Phase 2

Detailed Description:

The study will comprise a Screening Visit, Baseline Visit, a 24-week treatment period and a 12-week follow up period. The Screening Visit (Visit 1) will be conducted up to 10 weeks prior to the Baseline Visit (Visit 2) to determine eligibility. Adult subjects with a history of chronic Non-Tuberculosis Mycobacterial (NTM) infection with at least 2 positive cultures in the prior two years, of which at least one is within the last 6 months prior to Screening, will be considered for enrollment. Subjects should provide a positive NTM sputum culture at Screening to be eligible.

Two subgroups of subjects will be recruited:

  • Group 1: 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.
  • Group 2: 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.

The study will include 30 subjects.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Open-label, non-controlled, multicenter, pilot clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Non-controlled, Multicentre, Pilot Clinical Trial of Inhaled Molgramostim in Subjects With Antibiotic-resistant Non-tuberculosis Mycobacterial (NTM) Infection
Anticipated Study Start Date : February 1, 2018
Estimated Primary Completion Date : May 1, 2019
Estimated Study Completion Date : August 1, 2019

Arm Intervention/treatment
Experimental: Inhaled molgramostim/antimycobacterials
Inhaled molgramostim administered in subjects who remain sputum culture positive while currently on a multidrug Non-tuberculosis Mycobacterial (NTM) guideline based antimycobacterial regimen, which has been ongoing for at least 6 months prior to the Baseline Visit
Drug: Inhaled molgramostim
300 µg / dose molgramostim (recombinant human GM-CSF) for inhalation
Other Name: rh-GM-CSF
Experimental: Inhaled molgramostim
Inhaled molgramostim administered in subjects who remain sputum culture positive but have stopped a multidrug Non-tuberculosis 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
Drug: Inhaled molgramostim
300 µg / dose molgramostim (recombinant human GM-CSF) for inhalation
Other Name: rh-GM-CSF



Primary Outcome Measures :
  1. Number of subjects with sputum culture conversion to negative [ Time Frame: 24 weeks ]
    Sputum culture conversion is defined as at least three consecutive sputum samples without growth of non-tuberculosis mycobacteria during the treatment period.


Secondary Outcome Measures :
  1. Number of subjects with sputum smear conversion to negative [ Time Frame: 24 weeks ]
    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.

  2. Number of subjects with durable sputum culture conversion [ Time Frame: 36 weeks ]
    Durability is defined as sputum culture conversion at or before Week 24 and culture still negative for growth of non-tuberculosis mycobacteria at 12-weeks follow-up.

  3. Number of subjects with durable sputum smear conversion [ Time Frame: 36 weeks ]
    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.

  4. Change in semi-quantitative grade of number of NTM on microscopy of AFB stained sputum smears [ Time Frame: 36 weeks ]
  5. Change in semi-quantitative grade of sputum cultures [ Time Frame: 36 weeks ]
  6. Change in symptom scores (assessed using Lower Respiratory Tract Infections - Visual Analogue Scale (LRTI-VAS) [ Time Frame: 36 weeks ]
  7. Change in Quality of Life scores (assessed using Quality of Life Questionnaire - Bronchiectasis (QOL-B)) [ Time Frame: 36 weeks ]
  8. Change in Global Rating of Health (GRH) [ Time Frame: 36 weeks ]
  9. Change in body weight [ Time Frame: 36 weeks ]
  10. Change in 6-minute walk distance (6MWD) [ Time Frame: 36 weeks ]
  11. Change in oxygen desaturation during a 6-minute walk test (6MWT) [ Time Frame: 36 weeks ]
  12. Change in Borg CR10 scores for dyspnea during a 6MWT [ Time Frame: 36 weeks ]
  13. Number of adverse events (AEs) during the trial period [ Time Frame: 36 weeks ]
  14. Number of serious AEs (SAEs) during the trial period [ Time Frame: 36 weeks ]
  15. Number of adverse drug reactions (ADRs) during the trial period [ Time Frame: 36 weeks ]
  16. Number of severe AEs during the trial period [ Time Frame: 36 weeks ]
  17. Number of AEs leading to treatment discontinuation during the trial period [ Time Frame: 36 weeks ]
  18. Change in white blood cell counts (WBC) in blood [ Time Frame: 36 weeks ]
  19. Change in white cell differential counts in blood [ Time Frame: 36 weeks ]
  20. Change in Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) [ Time Frame: 24 weeks ]
  21. Change in forced expiratory volume in 1 second (FEV1) (% predicted) [ Time Frame: 24 weeks ]
  22. Change in forced vital capacity (FVC) (% predicted) [ Time Frame: 24 weeks ]
  23. Number of subjects with development of anti-molgramostim antibodies in serum [ Time Frame: 36 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03421743


Contacts
Contact: Mikkel Walmar, M.Sc. +45 79301413 mikkel.walmar@savarapharma.com
Contact: Cecilia Ganslandt, MD +45 79301413 cecilia.ganslandt@savarapharma.com

Sponsors and Collaborators
Savara Inc.
Investigators
Principal Investigator: Grant Waterer, Prof. Royal Perth Hospital

Responsible Party: Savara Inc.
ClinicalTrials.gov Identifier: NCT03421743     History of Changes
Other Study ID Numbers: SAV-008-01
First Posted: February 5, 2018    Key Record Dates
Last Update Posted: February 5, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Communicable Diseases
Mycobacterium Infections
Mycobacterium Infections, Nontuberculous
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Molgramostim
Anti-Bacterial Agents
Antineoplastic Agents
Anti-Infective Agents