IV Gallium treatment for cystic fibrosis patients with NTM infections

A Phase 1b, Multi-center Study of Intravenous (IV) Gallium Nitrate in Patients With Cystic Fibrosis (CF) Who Are Colonized With Nontuberculous Mycobacteria (NTM) (The ABATE Study)

This study is testing if IV gallium can safely help adults with cystic fibrosis who have NTM infections feel better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Seattle Children's Hospital (Academic / other)
• Locations: 10 sites (Birmingham, Alabama and 9 other locations)
• Trial ID: NCT04294043 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and tolerability of two 5-day infusion cycles of IV gallium in adult patients with cystic fibrosis who are infected with nontuberculous mycobacterium (NTM). It is a multicenter, open-label study that includes two cohorts: treatment-naïve patients and treatment-refractory patients. Participants will receive gallium nitrate infusions, and the study aims to assess both the safety and the antimycobacterial effects of the treatment.

Who should consider this trial

Good fit: Ideal candidates are adults with cystic fibrosis who have persistently positive NTM culture results and either have never been treated for NTM or have not responded to previous treatments.

Not a fit: Patients without a diagnosis of cystic fibrosis or those who do not have persistently positive NTM cultures may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for cystic fibrosis patients suffering from persistent NTM infections.

How similar studies have performed: While this approach is novel in the context of cystic fibrosis and NTM infections, similar studies using gallium in other contexts have shown promise.

Eligibility criteria

Inclusion Criteria for Treatment-Naïve NTM Cohort

1. Written informed consent obtained from participant or participant's legal representative
2. Be willing and able to adhere to the study visit schedule and other protocol requirements
3. All genders ≥ 18 years of age at Visit 1
4. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype
5. Documentation of persistently positive NTM culture results that are positive for the same species or sub-species (either M. avium complex, M. abscessus complex, or both M. avium and M. abscessus). Persistently positive cultures are those which meet ONE of the following criteria, after first ignoring any negative culture results that occur within 7 days of a positive culture:

   1. The two most recent NTM culture results from sputum or BAL taken at least 28 days apart are positive.

      OR
   2. At least one NTM culture result in the previous 4 months from sputum or BAL is positive. If there are four or more cultures in the last 12-months at least 3 out of the 4 most recent cultures must be positive for NTM. If there are three or fewer cultures in the past 12 months, then at least 2 of the 3 most recent cultures must be positive for NTM even if some of those cultures are more than 12 months ago.
6. Current NTM species or subspecies has never been treated or previous treatment was associated with clearance of NTM and completed \> 2 years prior to Day 1
7. FEV1 ≥ 25 % of predicted value at Screening
8. Able to expectorate sputum
9. Clinically stable with no significant changes in health status within 7 days prior to Day 1
10. Enrolled in the CFF Patient Registry (CFF PR)
11. Willing to discontinue chronic azithromycin use for the duration of the study

Inclusion Criteria for Treatment-Refractory NTM Cohort

1. Written informed consent obtained from participant or participant's legal representative
2. Be willing and able to adhere to the study visit schedule and other protocol requirements
3. All genders ≥ 18 years of age at Visit 1
4. Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype
5. History of current or prior treatment for NTM pulmonary disease with M. abscessus or M avium (or both M. avium and M. abscessus)

   1. Previously received treatment with guideline-based antibiotics for \>12 months without having treatment discontinued for reasons of culture clearance OR
   2. Currently receiving treatment with guideline-based antibiotics for \>12 months
6. FEV1 ≥ 25 % of predicted value at Screening
7. Able to expectorate sputum
8. Not hospitalized within 7 days prior to Day 1
9. Enrolled in the CFF Patient Registry (CFF PR)
10. Be willing and able to continue guideline-based antibiotic therapy for M. abscessus or M avium (or both M. avium and M. abscessus) concurrent with IV gallium, if currently on treatment

Exclusion Criteria Treatment-Naïve NTM Cohort

1. Any of the following abnormal lab values at screening:

   * Hemoglobin \<10g/dL
   * Platelets \<100,000/mm3
   * Absolute neutrophil count \< 1500/mm3
   * Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), or total bilirubin ≥3 x upper limit of normal
   * Serum creatinine \> 2.0 mg/dl and ≥1.5 x upper limit of normal
   * Ionized calcium ≤ lower limit of normal (only performed if total calcium is ≤ lower limit of normal)
2. History of solid organ or hematological transplantation
3. Use of bisphosphonates within 7 days prior to Day 1
4. Known sensitivity to gallium
5. Use of any investigational drug and/or participated in any interventional clinical trial within 28 days prior to Day 1
6. In the opinion of the Investigator, features of active NTM disease are present (e.g., clinical worsening is likely due to NTM disease despite definitive treatment of co-pathogens and/or acute exacerbations)
7. Undergoing treatment for NTM disease or anticipate beginning treatment within 3 months
8. Current diagnosis of osteoporosis
9. For people of childbearing potential:

   * Positive pregnancy test at Visit 1 or
   * Lactating or
   * Unwilling to practice a medically acceptable form of contraception (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal during the study
10. For people able to father a child: unwilling to use adequate contraception (as determined by the investigator) during the study
11. Has any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
12. New initiation of chronic CF therapy (e.g., CFTR modulators, ibuprofen, azithromycin, inhaled tobramycin, Cayston, etc.) within 28 days prior to Visit 1 (Day 1)
13. Use of azithromycin within 14 days prior to the screening visit

Exclusion Criteria Treatment-Refractory NTM Cohort

1. Any of the following abnormal lab values at screening:

   * Hemoglobin \<10g/dL
   * Platelets \<100,000/mm3
   * Absolute neutrophil count \< 1500/mm3
   * Aspartate transaminase (AST), alanine transaminase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP), or total bilirubin ≥3 x upper limit of normal
   * Serum creatinine \> 2.0 mg/dL and ≥1.5 x upper limit of normal
   * Ionized calcium ≤ lower limit of normal (only performed if total calcium is ≤ lower limit of normal)
2. History of solid organ or hematological transplantation
3. Use of bisphosphonates within 7 days prior to Day 1
4. Known sensitivity to gallium
5. Use of any investigational drug and/or participated in any interventional clinical trial within 28 days prior to Day 1
6. Current diagnosis of osteoporosis
7. For people of childbearing potential:

   * Positive pregnancy test at Visit 1 (Day 1) or
   * Lactating or
   * Unwilling to practice a medically acceptable form of contraception (acceptable forms of contraception: abstinence, hormonal birth control, intrauterine device, or barrier method plus a spermicidal agent), unless surgically sterilized or postmenopausal during the study
8. For people able to father a child: unwilling to use adequate contraception (as determined by the investigator) during the study
9. Has any other condition that, in the opinion of the Site Investigator/designee, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
10. New initiation of chronic CF therapy (e.g., CFTR modulators, ibuprofen, inhaled tobramycin, Cayston, etc.) within 28 days prior to Visit 1 (Day 1)

Where this trial is running

Birmingham, Alabama and 9 other locations

• University of Alabama at Birmingham — Birmingham, Alabama, United States (Recruiting)
• National Jewish Health — Denver, Colorado, United States (Recruiting)
• Johns Hopkins University — Baltimore, Maryland, United States (Recruiting)
• The Minnesota Cystic Fibrosis Center — Minneapolis, Minnesota, United States (Recruiting)
• Nationwide Children's Hospital — Columbus, Ohio, United States (Recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• Medical University of South Carolina — Charleston, South Carolina, United States (Recruiting)
• University of Texas Southwestern — Dallas, Texas, United States (Recruiting)
• University of Vermont Medical Center — Burlington, Vermont, United States (Recruiting)
• University of Washington Medical Center — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Christopher H. Goss, MD, MSc — University of Washington, Seattle Children's Hospital
• Study coordinator: Natallia Cameron

Conditions Nontuberculous Mycobacterium Infection; Cystic Fibrosis; Gallium Nitrate; IV Gallium; Nontuberculous mycobacterium; NTM; Mycobacterium abscessus; mycobacterium avium