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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 : December 2, 2020
Sponsor:
Information provided by (Responsible Party):
RedHill Biopharma Limited

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.

Condition or disease Intervention/treatment Phase
Pulmonary Mycobacterium Avium Complex Infection Bronchiectasis Lung Diseases Drug: RHB-204 Drug: Placebo Phase 3

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 125 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Study of RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex (MAC) Disease (CleaR-MAC Trial)
Actual Study Start Date : December 1, 2020
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Experimental: RHB-204
Each capsule contains clarithromycin 158.3mg; rifabutin 40mg; clofazimine 13.3mg.
Drug: RHB-204
RHB-204
Other Name: Clarithromycin 158.3mg, Rifabutin 40mg and Clofazimine 13.3mg

Placebo Comparator: Placebo
Matching placebo will contain riboflavin, a type of B vitamin, which may discolor urine in a similar fashion as RHB-204.
Drug: Placebo
Matching placebo to RHB-204




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

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): NCT04616924


Contacts
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Contact: Aida Bibliowicz, MSc. MBA +972 3 541 3131 aida@redhillbio.com
Contact: Gina Eagle, MD 972 (0)3 541 3131 ginaeagle@getpharmaconsulting.com

Locations
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United States, California
Medical Facility Not yet recruiting
Palm Springs, California, United States, 92262
United States, Connecticut
Medical Facility Not yet recruiting
Farmington, Connecticut, United States, 06030-1225
United States, District of Columbia
Medical Facility Not yet recruiting
Washington, District of Columbia, United States, 20007
United States, Florida
Medical Facility Not yet recruiting
Clearwater, Florida, United States, 33765
Medical Facility Not yet recruiting
Gainesville, Florida, United States, 32610
Medical Facility Not yet recruiting
Margate, Florida, United States, 33063
Medical Facility 1 Not yet recruiting
Orlando, Florida, United States, 32803
Medical Facility 2 Not yet recruiting
Orlando, Florida, United States, 32803
Medical Facility Not yet recruiting
Sebring, Florida, United States, 33870
Medical Facility Not yet recruiting
Vero Beach, Florida, United States, 32960
United States, Georgia
Medical Facility Not yet recruiting
Atlanta, Georgia, United States, 30342
Medical Facility Not yet recruiting
Valdosta, Georgia, United States, 31605
United States, Kansas
Medical Facility Not yet recruiting
Kansas City, Kansas, United States, 66160
United States, Louisiana
Medical Facility Not yet recruiting
New Orleans, Louisiana, United States, 70115
United States, Massachusetts
Medical Facility Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, Minnesota
Medical Facility Not yet recruiting
Rochester, Minnesota, United States, 55902
United States, Missouri
Medical Facility Not yet recruiting
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Medical Facility Not yet recruiting
Newark, New Jersey, United States, 07103
United States, New York
Medical Facility Not yet recruiting
New York, New York, United States, 10029
United States, North Carolina
Medical Facility Recruiting
Winston-Salem, North Carolina, United States, 27103
United States, Oregon
Medical Facility Not yet recruiting
Portland, Oregon, United States, 97239
United States, South Carolina
Medical Facility Not yet recruiting
Charleston, South Carolina, United States, 29425
United States, Texas
Medical Facility Not yet recruiting
Tyler, Texas, United States, 75708
United States, Wisconsin
Medical Facility Not yet recruiting
Wauwatosa, Wisconsin, United States, 53226
Sponsors and Collaborators
RedHill Biopharma Limited
Investigators
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Study Director: Kevin L. Winthrop, MD, MPH Oregon Health and Science University
Study Chair: June L Almenoff, MD, PhD RedHill Biopharma, Inc.
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Responsible Party: RedHill Biopharma Limited
ClinicalTrials.gov Identifier: NCT04616924    
Other Study ID Numbers: RHB-204-01
First Posted: November 5, 2020    Key Record Dates
Last Update Posted: December 2, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by RedHill Biopharma Limited:
MAC
Bronchiectasis
NTM
Additional relevant MeSH terms:
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Mycobacterium Infections
Mycobacterium avium-intracellulare Infection
Lung Diseases
Bronchiectasis
Respiratory Tract Diseases
Bronchial Diseases
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Mycobacterium Infections, Nontuberculous
Clarithromycin
Rifabutin
Clofazimine
Anti-Bacterial Agents
Anti-Infective Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Inflammatory Agents
Leprostatic Agents