Phase II Investigation of Antimycobacterial Therapy on Progressive, Pulmonary Sarcoidosis

NCT02024555 | Completed Phase 2 Results DMC

• 2 other identifiers: R01HL117074R01HL117074-01
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 6

Brief Summary

The primary purpose of this study is to investigate the efficacy and safety of oral antimycobacterial therapy in patients with confirmed progressive pulmonary sarcoidosis. We suspect that the CLEAR regimen will improve the absolute FVC percent predicted in chronic pulmonary sarcoidosis participants.

Conditions

Sarcoidosis; Antimycobacterial Therapy

Outcome Measures

Primary Outcomes (1)

• Change in Percent Predicted Absolute Forced Vital Capacity (FVC) in Participants With Pulmonary Sarcoidosis, Comparing Baseline With Performance After Completion of 16 Weeks of Therapy.

  Change in percent predicted absolute forced vital capacity (FVC) in participants with pulmonary sarcoidosis, comparing baseline with performance after completion of 16 weeks of therapy. This will involve comparing sarcoidosis and placebo after 16 weeks of therapy.

  Baseline to 16 weeks

Secondary Outcomes (11)

• Radiographic Improvement in Sarcoidosis Lung Disease by Frontal Chest X-ray .

  Baseline and 16 weeks

• Six Minute Walk, Distance in Meters

  Baseline, 4, 8, and 16 and 24 weeks

• Change in Oxygen Saturation

  Baseline, 4, 8, and 16 and 24 weeks

• Change in Level of Dyspnea

  Baseline, 4, 8 and 16 weeks

• Change in the Saint George's Respiratory Questionnaire (SGRQ)

  Baseline and 16 weeks

Study Arms (2)

Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin

ACTIVE COMPARATOR

Levofloxacin 500mg po QD; Ethambutol 1200mg po QD; Azithromycin 250 mg po QD; Rifampin 600mg po QD or Rifabutin 300mg po QD

Drug: Levofloxacin; Drug: Ethambutol; Drug: Azithromycin; Drug: Rifampin

Placebo

PLACEBO COMPARATOR

Riboflavin will be used for rifampin; encapsulated microcrystalline cellulose will be used to replace the levofloxacin, ethambutol and azithromycin. The pill count will be the same as the comparator regimen.

Drug: Placebo

Interventions

Levofloxacin DRUG

Also known as: Levaquin

Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin

Ethambutol DRUG

Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin

Azithromycin DRUG

Also known as: Z-pack

Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin

Rifampin DRUG

Also known as: Rifadin, Rimactane

Concomitant Levaquin, Ethambutol, Azithromycin and Rifampin

Placebo DRUG

This will serve as a placebo to the antibiotics used in antimycobacterial therapy.

Placebo

Eligibility Criteria

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

You may qualify if:

• Patients with sarcoidosis as defined by the ATS/ERS/WASOG statement on sarcoidosis as defined by the clinical presentation consistent with sarcoidosis, as well as biopsy demonstrating granulomas, and no alternative for the cause of the granulomas, such as tuberculosis for at least one year prior to randomization.
• Evidence of disease progression as defined by at least one of the following three criteria:
• Decline of absolute percent predicted of FVC (FVC ≥45% or higher of predicted value) or DLCO of at least 5% on serial measurements (DLCO range \>35%, if measured); Radiographic progression in chest imaging on side by side comparison; Change in dyspnea score, as measured by Transition Dyspnea Index (TDI); Positive peripheral immune responses to ESAT-6 as a biomarker of response to CLEAR regimen.
• Possess evidence of parenchymal or nodal disease on chest radiograph.

You may not qualify if:

• Inability to obtain consent
• Age less than 18 years
• Female participants of childbearing potential not willing to use one of the following methods of birth control for the duration of the study and 90 days after study completion: condoms, sponge, foams, jellies, diaphragm, non-hormonal intrauterine device, a vasectomized sole partner or abstinence. Note: Oral contraceptive pills are not effective birth control when taking rifamycin. A negative urine pregnancy test at screening visit if female of childbearing potential
• FVC predicted value is \< 45%.
• End-stage fibrotic pulmonary disease.
• Significant underlying liver disease.
• Allergy or intolerance to any of the antibiotics within the CLEAR regimen.
• Allergy or intolerance to albuterol
• Poor venous access for obtaining blood samples
• History of active tuberculosis, close contact with a person with active tuberculosis within the 6 months prior to the screening visit or has a positive PPD.
• Significant disorder, other than sarcoidosis, that would complicate the treatment evaluation, (such as respiratory, cardiac, neurologic, musculoskeletal or seizure disorders)
• Use of an investigational drug within 30 days prior to screening or within 5 half-lives of the agent, whichever is longer.
• Currently receiving \>40mg prednisone.
• ALT or AST \>5 times upper limit of normal (ULN)
• Leukopenia, as defined by WBC \<3.0 cells/mm3 or absolute neutrophil count \<1000

Sponsors & Collaborators

• Vanderbilt University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (6)

Albany Medical Center

Albany, New York, 12208, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Sarcoidosis

Interventions

Levofloxacin; Ethambutol; Azithromycin; Rifampin

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Erythromycin; Macrolides; Polyketides; Lactones; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Wonder Drake, MD
• Organization: Vanderbilt University Medical Center

wonder.drake@vumc.org

(615) 322-2035

Study Officials

• Wonder Drake, MD

  Vanderbilt University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: December 26, 2013
• First Posted: December 31, 2013
• Study Start: March 1, 2014
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: July 9, 2020
• Results First Posted: July 9, 2020

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)