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

NCT04616924 | Terminated Phase 3 FDA Drug

• 1 other identifier: RHB-204-01
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 25

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.

Conditions

Pulmonary Mycobacterium Avium Complex Infection; Bronchiectasis; Lung Diseases

Keywords

MAC; Bronchiectasis; NTM

Outcome Measures

Primary Outcomes (2)

• 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

  6 months

• 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.

  6 months

Secondary Outcomes (11)

• Part 1 Secondary efficacy objective - Reduction of fatigue

  6 months

• Part 1 Secondary efficacy objective - Time to culture conversion

  6 months

• Part 1 Secondary efficacy objective - Improvement in Physical Functioning

  6 months

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

  19 months

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

  16 months

Study Arms (2)

RHB-204

EXPERIMENTAL

Each capsule contains clarithromycin 158.3mg; rifabutin 40mg; clofazimine 13.3mg.

Drug: RHB-204

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

RHB-204 DRUG

RHB-204

Also known as: Clarithromycin 158.3mg, Rifabutin 40mg and Clofazimine 13.3mg

RHB-204

Placebo DRUG

Matching placebo to RHB-204

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• RedHill Biopharma Limited: lead

Study Sites (25)

Medical Facility

Glendale, California, 91205, United States

Location

Medical Facility

Palm Springs, California, 92262, United States

Location

Medical Facility

Farmington, Connecticut, 06030-1225, United States

Location

Medical Facility

Washington D.C., District of Columbia, 20007, United States

Location

Medical Facility

Clearwater, Florida, 33765, United States

Location

Medical Facility

Gainesville, Florida, 32610, United States

Location

Medical Facility

Margate, Florida, 33063, United States

Location

Medical Facility 1

Orlando, Florida, 32803, United States

Location

Medical Facility 2

Orlando, Florida, 32803, United States

Location

Medical Facility

Sebring, Florida, 33870, United States

Location

Medical Facility

Vero Beach, Florida, 32960, United States

Location

Medical Facility

Atlanta, Georgia, 30342, United States

Location

Medical Facility

Valdosta, Georgia, 31605, United States

Location

Medical Facility

Kansas City, Kansas, 66160, United States

Location

Medical Facility

New Orleans, Louisiana, 70112, United States

Location

Medical Facility

Boston, Massachusetts, 02215, United States

Location

Medical Facility

Rochester, Minnesota, 55902, United States

Location

Medical Facility

St Louis, Missouri, 63110, United States

Location

Medical Facility

Newark, New Jersey, 07103, United States

Location

Medical Facility

New York, New York, 10029, United States

Location

Medical Facility

Winston-Salem, North Carolina, 27103, United States

Location

Medical Facility

Portland, Oregon, 97239, United States

Location

Medical Facility

Charleston, South Carolina, 29425, United States

Location

Medical Facility

Tyler, Texas, 75708, United States

Location

Medical Facility

Wauwatosa, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Bronchiectasis; Lung Diseases

Interventions

Clarithromycin; Rifabutin; Clofazimine

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Phenazines; Heterocyclic Compounds, 3-Ring

Study Officials

• Kevin L. Winthrop, MD, MPH

  Oregon Health and Science University

  STUDY DIRECTOR

• June L Almenoff, MD, PhD

  RedHill Biopharma, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 19, 2020
• First Posted: November 5, 2020
• Study Start: December 1, 2020
• Primary Completion: August 28, 2023
• Study Completion: August 28, 2023
• Last Updated: March 18, 2025

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (25)