Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Azacytidine During Anti-tuberculosis Therapy (AZA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03941496
Recruitment Status : Not yet recruiting
First Posted : May 8, 2019
Last Update Posted : May 9, 2019
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Andrew Dinardo, Baylor College of Medicine

Brief Summary:

This is a Phase II single-institution, open-label, non-randomized clinical trial evaluating the safety of azacytidine in pulmonary tuberculosis (TB) patients after 6 months, 4 months and 2 months of Anti-Tuberculosis Therapy (ATT).

Participants will include HIV-uninfected individuals with microbiologically confirmed TB who have successful completed the intensive phase of anti-tuberculosis therapy.

All study participants will have drug-sensitive TB and successfully complete 2 months of standard intensive phase 4-drug RHZE (rifampin, isoniazid, pyrazinamide, ethambutol). By definition, to have uncomplicated TB, participants will have become asymptomatic and smear-negative by the end of intense phase anti-Tb therapy and be ready to transition from standard 4-drug (INH, RIF, ETH, PZA) intense phase to the 2-drug continuation phase (INH and RIF).


Condition or disease Intervention/treatment Phase
Tuberculosis, Pulmonary Drug: Azacitidine Injection [Vidaza] - Phase A Group Drug: Azacitidine Injection [Vidaza] - Phase B Group Drug: Azacitidine Injection [Vidaza] - Phase C Group Drug: Azacitidine Injection [Vidaza] - Phase D Group Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: after 24 weeks of successful ATT, 3 asymptomatic TB subjects that have become culture and smear negative will receive a cycle of AZA (SQ 75mg/m2 for 5 days). If a study participant experiences dose limiting toxicity (DLT; defined below), then 3 additional participants will be added to the current time point. If only 1 of 6 participants experience DLT/IRIS at a given time point, the study will proceed. If at least 2 of 6 patients experience a DLT at a time point, then the study will not proceed to the next phase. If 1 or less of the Phase A participants experience DLT, then the study will proceed to Phase B.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Immunogenicity of the DNMT Inhibitor Azacytidine During Anti-Tuberculosis Therapy
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Tuberculosis
Drug Information available for: Azacitidine

Arm Intervention/treatment
Experimental: Phase A Group
Phase A Group - AZA Treatment
Drug: Azacitidine Injection [Vidaza] - Phase A Group
3 TB subjects, that have become culture and smear negative after 6 months of successful ATT, will receive a cycle of AZA (SQ 75mg/m2 for 5 days). If a study participant experiences dose limiting toxicity (DLT; defined below), then 3 additional participants will be added to the current time point (n=6). If only 1 of 6 participants experience DLT/IRIS at a given time point, the study will proceed to the earlier time point. If at least 2 of 6 patients experience a DLT at a time point, then the study will not proceed to the next phase (Phase B).
Other Name: AZA - Phase A Group

Experimental: Phase B Group
Phase B Group - AZA Treatment
Drug: Azacitidine Injection [Vidaza] - Phase B Group
3 TB subjects, that have become culture and smear negative after 4 months (+/- 14 days) of successful ATT, will receive a cycle of AZA (SQ 75mg/m2 for 5 days). If a study participant experiences dose limiting toxicity (DLT; defined below), then 3 additional participants will be added to the current time point (n=6). If at least 2 of 6 patients experience a DLT at a time point, then the study will not proceed to the next phase (Phase C).
Other Name: AZA - Phase B Group

Experimental: Phase C Group
Phase C Group - AZA Treatment
Drug: Azacitidine Injection [Vidaza] - Phase C Group
3 TB subjects, that have become culture and smear negative after 8-10 weeks of successful ATT, will receive a cycle of AZA (SQ 75mg/m2 for 5 days). If a study participant experiences dose limiting toxicity (DLT; defined below), then 3 additional participants will be added to the current time point (n=6). If at least 2 of 6 patients experience a DLT at a time point, then the study will not proceed to the next phase (Phase D).
Other Name: AZA - Phase C Group

Experimental: Phase D Group
Phase D Group - AZA Treatment
Drug: Azacitidine Injection [Vidaza] - Phase D Group
21 TB subjects, that have become culture and smear negative after 8-10 weeks of successful ATT, will receive a cycle of AZA (SQ 75mg/m2 for 5 days).
Other Name: AZA - Phase C Group

No Intervention: Control Group
24 controls will not receive study drug



Primary Outcome Measures :
  1. Overall incidence of all IP-related adverse events [ Time Frame: 2 years ]
    using Common Toxicity Criteria v 4.0.

  2. Overall severity of all IP-related adverse events [ Time Frame: 2 years ]
    using Common Toxicity Criteria v 4.0.

  3. Measurement of epigenetic-mediated immune exhaustion [ Time Frame: 2 years ]
    measured by using 1) a standardized mycobacterial growth inhibition assay (MGIA) that measures ex vivo mycobacterial killing; 2) 18-parameter flow cytometry based multi-dimensional immune profiling (MDIP); and 3) epigenetic assays



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age 18 years or older
  2. Microbiologically confirmed pulmonary Tuberculosis.
  3. Asymptomatic by the end of intense phase ATT (2 months) and remains asymptomatic until AZA dosing.
  4. AFB-smear negative at the end of intensive phase.
  5. 1-month culture with >28 days TTP (time to positivity).
  6. HIV-negative.
  7. Adequate hepatic function (direct bilirubin < 2 x upper limit of normal (ULN), ALT and/or AST 2x ULN or less) at the end of ATT intensive phase.
  8. Adequate renal function (creatinine 2 mg/dl or less).
  9. Written informed consent obtained
  10. Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months after the last treatment.

Exclusion Criteria:

  1. HIV-infection
  2. Smear-positive at 2 months
  3. 1-month sputum culture positive with less than 28 days TTP.
  4. Participants with extrapulmonary TB.
  5. h drug-resistant tuberculosis
  6. After consent and within two weeks before Investigational Product (IP), a study CBC will be performed and individuals with cytopenias (Hemoglobin less than 12 g/dL, WBC less than 3 cells/ mL^3 or less than 110. Platelets per μL) will be excluded.
  7. Any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.
  8. Pregnant or breast feeding females. (Lactating females must agree not to breast feed while taking azacytidine).
  9. Uncontrolled systemic fungal, bacterial or viral infection (defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment)
  10. History of inflammatory bowel disease (eg, Crohn¿s disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect that would interfere with the absorption, distribution, metabolism or excretion of the study drug and/or predispose the subject to an increased risk of gastrointestinal toxicity
  11. Abnormal coagulation parameters (PT >15 seconds, PTT >40 seconds, and/or INR >1.5)
  12. Significant active cardiac disease within the previous 6 months including:

    1. NYHA class 4 CHF
    2. Unstable angina
    3. Myocardial infarction
  13. Active viral infection with HIV or hepatitis type B or C
  14. Known or suspected hypersensitivity to azacytidine or mannitol
  15. Inability to give informed consent.

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): NCT03941496


Contacts
Layout table for location contacts
Contact: Andrew DiNardo 832.822-1331 dinardo@bcm.edu

Locations
Layout table for location information
United States, Texas
Harris Health System - Ben Taub Hospital Not yet recruiting
Houston, Texas, United States, 77030
Contact: Andrew DiNardo, MD         
Sub-Investigator: Elizabeth Guy, MD         
Sub-Investigator: Elizabeth Chiao, MD         
Sub-Investigator: Cristian Coarfa, PhD         
Sub-Investigator: Kimal Rajapakshe, PhD         
Sponsors and Collaborators
Andrew Dinardo
Celgene Corporation
Investigators
Layout table for investigator information
Principal Investigator: Andrew DiNardo Baylor College of Medicine

Layout table for additonal information
Responsible Party: Andrew Dinardo, Principal Investigator / Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT03941496     History of Changes
Other Study ID Numbers: H-45051
First Posted: May 8, 2019    Key Record Dates
Last Update Posted: May 9, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Andrew Dinardo, Baylor College of Medicine:
Tuberculosis
TB
Mycobacterium tuberculosis
Mtb
anti-TB therapy
ATT
rifampin (R), isoniazid (H) pyrazinamide (Z) ethambutol (E)
RHZE
rifampin (R), isoniazid (H)
RH

Additional relevant MeSH terms:
Layout table for MeSH terms
Tuberculosis
Tuberculosis, Pulmonary
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Azacitidine
Rifampin
Isoniazid
Antitubercular Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors
Antibiotics, Antitubercular
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers
Fatty Acid Synthesis Inhibitors