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RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex Disease (CleaR-MAC)

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ClinicalTrials.gov Identifier: NCT04616924
Recruitment Status : Recruiting
First Posted : November 5, 2020
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

Tracking Information
First Submitted Date  ICMJE October 19, 2020
First Posted Date  ICMJE November 5, 2020
Last Update Posted Date May 12, 2021
Actual Study Start Date  ICMJE December 1, 2020
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 4, 2020)
Sputum culture conversion (SCC) [ Time Frame: 6 months ]
The proportion of subjects who achieve SCC by Month 6. This will be evaluated at Month 6 whereby SCC is defined by at least 3 prior consecutive negative monthly sputum cultures at Month 6.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 4, 2020)
  • Part 1 Secondary efficacy objective - Quality of Life Physical Functioning Symptoms [ Time Frame: 6 months ]
    The mean change in the Short Form 36 Survey - Physical Functioning domain score from baseline to Month 6 for RHB-204 compared to placebo. The Physical Functioning Domain is scored out of 100, whereby a score of 100 is the best a patient can function.
  • Part 1 Secondary efficacy objective - Reduction of fatigue [ Time Frame: 6 months ]
    The mean change in the PROMIS Fatigue SF 8a score from baseline to Month 6 for RHB-204 compared to placebo. The PROMIS Fatigue SF 8a is scored out of 40, whereby a score of 40 is the worst a patient can feel.
  • Part 1 Secondary efficacy objective - Time to culture conversion [ Time Frame: 6 months ]
    The time to SCC (month of first negative sputum culture) for RHB-204 compared to placebo.
  • Part 1 Secondary efficacy objective - Improvement in Quality of Life - Respiratory Symptoms [ Time Frame: 6 months ]
    To asses the improvement in the the Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo. The Quality of Life Questionnaire-Bronchiectasis (QoL-B) Respiratory Symptoms domain score is scored out of 32 (excluding sputum color answers) whereby a score of 32 is the best a patient's respiratory symptoms can be.
  • Part 2 Secondary efficacy objective - Quality of Life Physical - Functioning Symptoms [ Time Frame: 19 months ]
    The mean change in the Short Form 36 Survey - Physical Functioning domain score from baseline to Month 19 for RHB-204 compared to placebo. The Physical Functioning Domain is scored out of 100, whereby a score of 100 is the best a patient can function.
  • Part 2 Secondary efficacy objective - Durable Sputum culture conversion at end of study [ Time Frame: 19 months ]
    The proportion of subjects with SCC by Month 6 who sustain negative sputum cultures at Month 16 and negative sputum culture at Month 19 (3 months off treatment) for RHB-204 compared to placebo (durable responders).
  • Part 2 Secondary efficacy objective - Durable Sputum culture conversion at end of treatment [ Time Frame: 16 months ]
    Measure the proportion of subjects with SCC by Month 6 who sustain negative sputum cultures at Month 16 for RHB-204 compared to placebo.
  • Part 2 Secondary efficacy objective - Improvement in Quality of Life - Fatigue 19 Months [ Time Frame: 19 months ]
    The mean change in the PROMIS Fatigue SF 8a score from baseline to Month 19 for RHB-204 compared to placebo. The PROMIS Fatigue SF 8a is scored out of 40, whereby a score of 40 is the worst a patient can feel.
  • Part 2 Secondary efficacy objective - Improvement in Quality of Life - Respiratory Symptoms [ Time Frame: 19 months ]
    The change in the Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms domain score from baseline to Month 19 for RHB-204 compared to placebo. The Quality of Life Questionnaire-Bronchiectasis (QoL-B) Respiratory Symptoms domain score is scored out of 32 (excluding sputum color answers) whereby a score of 32 is the best a patient's respiratory symptoms can be.
  • Part 2 Secondary efficacy objective - Quality of Life Physical Functioning Symptoms [ Time Frame: 16 months ]
    The mean change in the Short Form 36 Survey - Physical Functioning domain score from baseline to Month 16 for RHB-204 compared to placebo. The Physical Functioning Domain is scored out of 100, whereby a score of 100 is the best a patient can function.
  • Part 2 Secondary efficacy objective - Improvement in Quality of Life - Fatigue 16 months [ Time Frame: 16 months ]
    The mean change in the PROMIS Fatigue SF 8a score from baseline to Month 16 for RHB-204 compared to placebo. The PROMIS Fatigue SF 8a is scored out of 40, whereby a score of 40 is the worst a patient can feel.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex Disease
Official Title  ICMJE Study of RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex (MAC) Disease (CleaR-MAC Trial)
Brief Summary A 2-part multi-center, Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of RHB-204 in adult subjects with underlying nodular bronchiectasis and documented MAC lung infection.
Detailed Description

A 2-part multi-center, Phase 3, randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of RHB-204 in adult subjects with underlying nodular bronchiectasis and documented MAC lung infection.

The primary efficacy endpoint evaluates sputum culture conversion evaluated at Month 6 (and defined as at least 3 prior consecutive negative monthly sputum cultures at Month 6).

Subjects remain on study drug in Part 2 until Month 16.

Patient reported outcomes and durability of microbiological response will be assessed at Month 6 and Month 19 (3 months post-completion of treatment).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Pulmonary Mycobacterium Avium Complex Infection
  • Bronchiectasis
  • Lung Diseases
Intervention  ICMJE
  • Drug: RHB-204
    RHB-204
    Other Name: Clarithromycin 158.3mg, Rifabutin 40mg and Clofazimine 13.3mg
  • Drug: Placebo
    Matching placebo to RHB-204
Study Arms  ICMJE
  • Experimental: RHB-204
    Each capsule contains clarithromycin 158.3mg; rifabutin 40mg; clofazimine 13.3mg.
    Intervention: Drug: RHB-204
  • Placebo Comparator: Placebo
    Matching placebo will contain riboflavin, a type of B vitamin, which may discolor urine in a similar fashion as RHB-204.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 4, 2020)
125
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2023
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  1. Males and females aged ≥18 years to ≤85 years of age, inclusively
  2. Have a MAC lung infection documented by at least 2 positive cultures for MAC 12 months prior to screening, with at least one of them obtained within 3 months prior to randomization.
  3. Have MAC lung infection with evidence of underlying nodular infiltrates and/or bronchiectasis on a chest computed tomography (Chest CT) within 6 months of screening.
  4. Have symptoms of MAC lung infection that include one of the following: respiratory symptoms such as chronic cough, excessive mucous production, fatigue, dyspnea, hemoptysis or systemic symptoms such as fever, night sweats or loss of appetite.
  5. Be treatment naïve, or if previously treated for MAC, have not received treatment within the 6 months prior to screening

Key Exclusion Criteria

  1. Cavitary lung disease as observed on a chest CT scan (cavitary lesions exceeding 2 cm in diameter).
  2. Currently taking or treated in the 6 months prior to screening with any of the following: bedaquiline, clofazimine or any component of American Thoracic Society(ATS)/Infectious Diseases Society of America (IDSA) multi-drug recommended therapy (macrolides, ethambutol, rifabutins/rifampins) for MAC or other multi-drug regime for NTM lung disease
  3. Clarithromycin minimum inhibitory concentration (MIC) ≥32μg/mL on MAC isolates in screening sputum
  4. Known hypersensitivity or suspected history of hypersensitivity reactions to clarithromycin, rifabutin, or clofazimine or other drugs in each class
  5. Subjects requiring chronic supplemental oxygen use (including intermittent or continuous use)
  6. Planned lung resection surgery for MAC lung disease
  7. Subjects with Cystic Fibrosis, prior solid organ or hematologic transplant
  8. Current usage of inhaled products containing amikacin, tobramycin or gentamicin
  9. History of ventricular arrhythmias or family history of Long QT syndrome, including torsades de pointes
  10. Corrected QT (QTc) interval on electrocardiogram (ECG) >460 ms for females or >450 ms for males, calculated using Fridericia's formula (QTcF)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Aida Bibliowicz, MSc. MBA +972 3 541 3131 aida@redhillbio.com
Contact: Gina Eagle, MD 972 (0)3 541 3131 ginaeagle@getpharmaconsulting.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04616924
Other Study ID Numbers  ICMJE RHB-204-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party RedHill Biopharma Limited
Study Sponsor  ICMJE RedHill Biopharma Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kevin L. Winthrop, MD, MPH Oregon Health and Science University
Study Chair: June L Almenoff, MD, PhD RedHill Biopharma, Inc.
PRS Account RedHill Biopharma Limited
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP