CleaR-MAC: RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex Disease
Study Details
Study Description
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 |
|---|---|---|
|
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 co-primary efficacy endpoints at the end of Part 1 evaluate the proportion of patients with sputum culture conversion after 6 months of treatment defined as three consecutive monthly negative sputum cultures at Months 4, 5, and 6 for RHB-204 compared to placebo and the mean change in the Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo.
At the Month 6 visit (end of Part 1), after all assessments including questionnaires and sputum samples have been collected, subjects will enter Part 2 of the study and receive open-label RHB-204 for 10 months to Month 16, followed by a post-treatment follow-up visit 3 months later, at Month 19.
Patient reported outcomes and durability of microbiological response will be assessed at Month 6 and Month 19 (3 months post-completion of treatment).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: RHB-204 Each capsule contains clarithromycin 158.3mg; rifabutin 40mg; clofazimine 13.3mg. |
Drug: RHB-204
RHB-204
Other Names:
|
| 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
|
Outcome Measures
Primary Outcome Measures
- Quality of Life Questionnaire - Bronchiectasis (QoL B) Respiratory Symptoms domain score [6 months]
The mean change in the Quality of Life Questionnaire - Bronchiectasis (QoL B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo
- Sputum culture conversion (SCC) [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
- Part 1 Secondary efficacy objective - Reduction of fatigue [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 [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 Physical Functioning [6 months]
The mean change in the Short Form 36 Physical Functioning domain score from baseline to Month 6 for RHB-204 compared to placebo.
- Part 2 Secondary efficacy objective - Durable Sputum culture conversion at end of study [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 [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.
- QoL B Respiratory Symptoms domain score mean change from baseline to Month 16 [16 months]
The mean change in Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms domain scores from baseline to Month 16 for ex-RHB-204 compared to ex-placebo
- Part 2 Secondary efficacy objective - Improvement in Quality of Life - Fatigue 16 months [16 months]
The mean change in the PROMIS Fatigue SF 8a score from baseline to Month 16 for ex-RHB-204 compared to ex-placebo
- Part 2 Secondary efficacy objective - Improvement in Quality of Life - Fatigue 19 Months [19 months]
The mean change in the PROMIS Fatigue SF 8a score from baseline to Month 19 for ex-RHB-204 compared to ex-placebo
- Part 2 Secondary efficacy objective - Quality of Life Physical Functioning Symptoms 16 Months [16 months]
The mean change in the Short Form 36 Physical Functioning domain score from baseline to Month 16 for ex-RHB-204 compared to ex-placebo
- Part 2 Secondary efficacy objective - Quality of Life Physical Functioning Symptoms 19 Months [19 Months]
The mean change in the Short Form 36 Physical Functioning domain score from baseline to Month 19 for ex-RHB-204 compared to ex-placebo
- QoL-B Respiratory Symptoms domain scores at Month 19 [19 Months]
The mean change in Quality of Life Questionnaire - Bronchiectasis (QoL-B) Respiratory Symptoms domain scores from baseline to Month 19 for ex-RHB-204 compared to ex-placebo
Eligibility Criteria
Criteria
Key Inclusion Criteria
-
Males and females aged ≥18 years to ≤85 years of age, inclusively
-
Have a MAC lung infection documented by one MAC positive culture within 18 months prior to screening and a MAC positive culture at screening (cultures need to be at least 1 month apart). Prior sputum for culture may be obtained from sputum or bronchial washings however, sputum collected during screening must be either spontaneously expectorated by the patient or after sputum induction.
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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.
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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.
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Be treatment naïve, or if previously treated for MAC, have not received treatment within the 6 months prior to screening
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Subject's weight is above 41 Kilograms or 90 pounds.
Key Exclusion Criteria
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Cavitary lung disease as observed on a chest CT scan (cavitary lesions exceeding 2 cm in diameter).
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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
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Clarithromycin minimum inhibitory concentration (MIC) ≥32μg/mL on MAC isolates in screening sputum
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Known hypersensitivity or suspected history of hypersensitivity reactions to clarithromycin, rifabutin, or clofazimine or other drugs in each class
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Subjects requiring chronic supplemental oxygen use (including intermittent or continuous use)
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Planned lung resection surgery for MAC lung disease
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Subjects with Cystic Fibrosis, prior solid organ or hematologic transplant
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Current usage of inhaled products containing amikacin, tobramycin or gentamicin
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History of ventricular arrhythmias or family history of Long QT syndrome, including torsades de pointes
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Corrected QT (QTc) interval on electrocardiogram (ECG) >460 ms for females or >450 ms for males, calculated using Fridericia's formula (QTcF)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical Facility | Glendale | California | United States | 91205 |
| 2 | Medical Facility | Palm Springs | California | United States | 92262 |
| 3 | Medical Facility | Farmington | Connecticut | United States | 06030-1225 |
| 4 | Medical Facility | Washington | District of Columbia | United States | 20007 |
| 5 | Medical Facility | Clearwater | Florida | United States | 33765 |
| 6 | Medical Facility | Gainesville | Florida | United States | 32610 |
| 7 | Medical Facility | Margate | Florida | United States | 33063 |
| 8 | Medical Facility 1 | Orlando | Florida | United States | 32803 |
| 9 | Medical Facility 2 | Orlando | Florida | United States | 32803 |
| 10 | Medical Facility | Sebring | Florida | United States | 33870 |
| 11 | Medical Facility | Vero Beach | Florida | United States | 32960 |
| 12 | Medical Facility | Atlanta | Georgia | United States | 30342 |
| 13 | Medical Facility | Valdosta | Georgia | United States | 31605 |
| 14 | Medical Facility | Kansas City | Kansas | United States | 66160 |
| 15 | Medical Facility | New Orleans | Louisiana | United States | 70112 |
| 16 | Medical Facility | Boston | Massachusetts | United States | 02215 |
| 17 | Medical Facility | Rochester | Minnesota | United States | 55902 |
| 18 | Medical Facility | Saint Louis | Missouri | United States | 63110 |
| 19 | Medical Facility | Newark | New Jersey | United States | 07103 |
| 20 | Medical Facility | New York | New York | United States | 10029 |
| 21 | Medical Facility | Winston-Salem | North Carolina | United States | 27103 |
| 22 | Medical Facility | Portland | Oregon | United States | 97239 |
| 23 | Medical Facility | Charleston | South Carolina | United States | 29425 |
| 24 | Medical Facility | Tyler | Texas | United States | 75708 |
| 25 | Medical Facility | Wauwatosa | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- RedHill Biopharma Limited
Investigators
- Study Director: Kevin L. Winthrop, MD, MPH, Oregon Health and Science University
- Study Chair: June L Almenoff, MD, PhD, RedHill Biopharma, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- RHB-204-01