Treatment-resistant pulmonary non-tuberculosis mycobacterial (NTM) infection MedDRA version: 20.1 Level: PT Classification code 10062207 Term: Mycobacterial infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: Molgramostim nebuliser solution (Molgradex)
Pharmaceutical Form: Nebuliser solution
INN or Proposed INN: MOLGRAMOSTIM
CAS Number: 99283-10-0
Other descriptive name: Recombinant human Gra
Sponsors
Savara ApS
Eligibility
Sex/Gender
All
Inclusion 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: o 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 o 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 1), 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. 1) Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: 1. Subjects diagnosed with cystic fibrosis. 2. Prior therapy with inhaled or systemic rhGM-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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main purpose of this study is to investigate if molgramostim can clear NTM infection from the sputum (phlegm) after 24 weeks of treatment.;Secondary Objective: The secondary objectives are to investigate the effect of molgramostrim on ability to exercise and weight loss and any improvement in the patient's symptoms and quality of life after 24 weeks of treatment.;Primary end point(s): Sputum culture conversion defined as at least three consecutive negative sputum samples during the treatment period.;Timepoint(s) of evaluation of this end point: During the treatment period (48 weeks). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Sputum smear conversion defined as at least three consecutive negative acid-fast bacilli (AFB) stained sputum smears on microscopy during the treatment period in subjects who were smear positive at Baseline. • Durability of sputum culture conversion (defined as conversion at or before Week 48 and culture still negative at 12-weeks follow-up). • Durability of sputum smear conversion (defined as conversion at or before Week 48 and smear still negative at 12-weeks follow-up). • Change in semi-quantitative grade of number of NTM on microscopy of AFB stained sputum smears from Baseline to Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 12-week follow-up. • Change in semi-quantitative grade of sputum cultures from Baseline to Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 12-week follow-up. • Change in symptom scores (assessed using Lower Respiratory Tract Infections – Visual Analogue Scale (LRTI-VAS) and Quality of Life Questionnaire– Bronchiectasis (QOLB) from Baseline to Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 12-week follow-up. • Change in Global Rating of Health (GRH) from Baseline to Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 12-week follow-up. • Change in body weight from Baseline to Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 12-week follow-up. • Change in 6-minute walk distance (6MWD), oxygen desaturation and Borg CR10 scores during a 6MWT from Baseline to Week 12, 24, 48 and 12-week follow-up.;Timepoint(s) of evaluation of this end point: • Sputum smear conversion: during the treatment period • Durability of sputum culture conversion and sputum smear conversion: up to Week 48 and at 12-weeks follow-up • Change in semi-quantitative grade of number of NTM, semi-quantitative grade of sputum cultures, symptom scores, GRH & body weight: from Baseline to Weeks 4, 8, 12, 16, 20, 24, 32, 40, 48 and 12-week follow-up • Change in 6MWD, oxygen desaturation and Borg CR10 scores: from Baseline to Week 12, 24, 48 and 12-week follo | — |
Countries
Australia, United Kingdom
Contacts
Public ContactRegulatory Affairs
Savara ApS
Outcome results
None listed