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Pulmonary Mycobacterium Avium Complex InfectionPhase 3CleaR-MACNCT04616924

RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex Disease

A Phase 3 study testing RHB-204 in people with Pulmonary Mycobacterium Avium Complex Infection and Bronchiectasis, run by RedHill Biopharma Limited at 25 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
RHB-204
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
12 participants
Where
25 sitesUnited States
Study dates
1 Dec 2020to 28 Aug 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
  • Be treatment naïve, or if previously treated for MAC, have not received treatment within the 6 months prior to screening
  • Subject's weight is above 41 Kilograms or 90 pounds.

Who cannot join

  • Cavitary lung disease as observed on a chest CT scan (cavitary lesions exceeding 2 cm in diameter).
  • 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
  • Clarithromycin minimum inhibitory concentration (MIC) ≥32μg/mL on MAC isolates in screening sputum
  • Known hypersensitivity or suspected history of hypersensitivity reactions to clarithromycin, rifabutin, or clofazimine or other drugs in each class
  • Subjects requiring chronic supplemental oxygen use (including intermittent or continuous use)
  • Planned lung resection surgery for MAC lung disease
Show all 10Show fewer
  • Subjects with Cystic Fibrosis, prior solid organ or hematologic transplant
  • Current usage of inhaled products containing amikacin, tobramycin or gentamicin
  • History of ventricular arrhythmias or family history of Long QT syndrome, including torsades de pointes
  • Corrected QT (QTc) interval on electrocardiogram (ECG) >460 ms for females or >450 ms for males, calculated using Fridericia's formula (QTcF)

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites
  • Medical Facility

    Atlanta, Georgia, 30342

  • Medical Facility

    Boston, Massachusetts, 02215

  • Medical Facility

    Charleston, South Carolina, 29425

  • Medical Facility

    Clearwater, Florida, 33765

  • Medical Facility

    Farmington, Connecticut, 06030-1225

  • Medical Facility

    Gainesville, Florida, 32610

  • Medical Facility

    Glendale, California, 91205

  • Medical Facility

    Kansas City, Kansas, 66160

  • Medical Facility

    Margate, Florida, 33063

  • Medical Facility

    New Orleans, Louisiana, 70112

  • Medical Facility

    New York, New York, 10029

  • Medical Facility

    Newark, New Jersey, 07103

  • Medical Facility 1

    Orlando, Florida, 32803

  • Medical Facility 2

    Orlando, Florida, 32803

  • Medical Facility

    Palm Springs, California, 92262

  • Medical Facility

    Portland, Oregon, 97239

  • Medical Facility

    Rochester, Minnesota, 55902

  • Medical Facility

    Sebring, Florida, 33870

  • Medical Facility

    St Louis, Missouri, 63110

  • Medical Facility

    Tyler, Texas, 75708

  • Medical Facility

    Valdosta, Georgia, 31605

  • Medical Facility

    Vero Beach, Florida, 32960

  • Medical Facility

    Washington D.C., District of Columbia, 20007

  • Medical Facility

    Wauwatosa, Wisconsin, 53226

  • Medical Facility

    Winston-Salem, North Carolina, 27103

Other trials in United States

About this study

Official title: Study of RHB-204 for the Treatment of Pulmonary Mycobacterium Avium Complex (MAC) Disease in Adults With Nodular Bronchiectasis (CleaR-MAC Trial)

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.

Read the 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.

In order to comply with current treatment duration guidelines (Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium avium Complex: Developing Drugs for Treatment - FDA Draft Guidance September 2021) in this protocol subjects will receive active treatment for 12 months after sputum culture conversion. As such, each subject's first negative culture that defines conversion will determine the total duration of their active study drug treatment. The longest duration of active study drug treatment will be 16 months. At the end of study treatment, all subjects will enter a 3-month post-treatment follow-up period (see study design section below for additional details).

To maintain the blind and integrity of the data, an independent team (Sputum Culture Monitors) will inform sites on each subject's treatment duration based on sputum culture conversion. Sputum Culture Monitors will also have access to randomized treatment allocation. All other study related personnel will remain blinded to sputum culture results and treatment allocation (Sponsor, CRO, medical monitors, safety, ECG and sputum laboratories, site personnel as well as participating subjects).

During Part 1, subjects who have completed at least the first 3 months of treatment with study drug, and at the Investigator's discretion, require rescue therapy (alternative anti-NTM treatment) will discontinue study drug (performing an EOT visit) and remain in the study to complete all scheduled study visits and assessments/procedures to Month 6 (performing an EOS visit).

Subjects who complete treatment based on the timeline provided by the Sputum Culture Monitors (EOT visit) and have an ongoing negative sputum culture will be reconsented to enter a follow-up Extension Study, to evaluate sputum culture results at two (2) further time points: 6 months and 12 months following end of treatment (EOT) for each subject in protocol RHB-204-01.

Being tested
RHB-204, Placebo
Keywords
MAC, Bronchiectasis, NTM
Medical subject headings
Bronchiectasis, Lung Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RHB-204Drug

    Also called Clarithromycin 158.3mg, Rifabutin 40mg and Clofazimine 13.3mg

    RHB-204

  • PlaceboDrug

    Matching placebo to RHB-204

Study groups in NCT04616924
Study groupRoleWhat they receive
RHB-204ExperimentalEach capsule contains clarithromycin 158.3mg; rifabutin 40mg; clofazimine 13.3mg.
Receives: Drug: RHB-204
PlaceboPlacebo comparatorMatching placebo will contain riboflavin, a type of B vitamin, which may discolor urine in a similar fashion as RHB-204.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Quality of Life Questionnaire - Bronchiectasis (QoL B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo

    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

    Measured: 6 months

  2. Sputum culture conversion (SCC)

    The proportion of subjects who achieve SCC by Month 6, defined by 3 consecutive monthly negative sputum cultures, without reversion, at Months 4, 5 \& 6 for THB-204 compared to placebo.

    Measured: 6 months

Secondary outcomes (11)
  1. Part 1 Secondary efficacy objective - Reduction of fatigue

    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 score from baseline to Month 6 for RHB-204 compared to placebo.

    Measured: 6 months

  2. Part 1 Secondary efficacy objective - Time to culture conversion

    The time to SCC (month of first negative sputum culture) for RHB-204 compared to placebo.

    Measured: 6 months

  3. Part 1 Secondary efficacy objective - Improvement in Physical Functioning

    The mean change in the Short Form 36 Physical Functioning domain score from baseline to Month 6 for RHB-204 compared to placebo.

    Measured: 6 months

  4. Part 2 Secondary efficacy objective - Durable Sputum culture conversion at end of study

    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).

    Measured: 19 months

  5. Part 2 Secondary efficacy objective - Durable Sputum culture conversion at end of treatment

    Measure the proportion of subjects with SCC by Month 6 who sustain negative sputum cultures at Month 16 for RHB-204 compared to placebo.

    Measured: 16 months

  6. QoL B Respiratory Symptoms domain score mean change from baseline to Month 16

    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

    Measured: 16 months

  7. Part 2 Secondary efficacy objective - Improvement in Quality of Life - Fatigue 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

    Measured: 16 months

  8. Part 2 Secondary efficacy objective - Improvement in Quality of Life - Fatigue 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

    Measured: 19 months

  9. Part 2 Secondary efficacy objective - Quality of Life Physical Functioning Symptoms 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

    Measured: 16 months

  10. Part 2 Secondary efficacy objective - Quality of Life Physical Functioning Symptoms 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

    Measured: 19 Months

  11. QoL-B Respiratory Symptoms domain scores at Month 19

    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

    Measured: 19 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2020
  2. Study start1 Dec 2020
  3. Primary completion28 Aug 2023
  4. Study completion28 Aug 2023

Why it stopped: extremely slow enrollment into study

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
12 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04616924
Sponsor's protocol ID
RHB-204-01
Acronym
CleaR-MAC
Status last verified
Jun 2023
First submitted
19 Oct 2020
Last updated
18 Mar 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing RHB-204 in people with Pulmonary Mycobacterium Avium Complex Infection and Bronchiectasis, run by RedHill Biopharma Limited at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 18 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: extremely slow enrollment into study). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Quality of Life Questionnaire - Bronchiectasis (QoL B) Respiratory Symptoms domain score from baseline to Month 6 for RHB-204 compared to placebo (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2025.

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