Azacytidine During Anti-tuberculosis Therapy

• Status: Not yet recruiting
• Trial end date: 2022-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Tuberculosis has been shown to make immune genes inaccessible and slows immune response The purpose of this research is to see if if azacitidine is safe and can return the ability of the body to resist tuberculosis (TB), a contagious infection that attacks the lungs. Individuals with tuberculosis are being asked to participate. Some will receive a drug to restore a host immunity while others can choose to receive standard of care. All patients will continue to receive standard of care tuberculosis therapy regardless of whether they chose to participate in the study.

This study is a Phase Ib/IIa single-institution, open-label, non-randomized clinical trial of sub-cutaneous azacitidine in pulmonary TB patients during the continuation phase of ATT.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Andrew Dinardo
• Collaborators: Bristol-Myers Squibb; Celgene Corporation
• Treatments: Antitubercular Agents; Azacitidine; Isoniazid; Rifampin

Criteria

Inclusion Criteria:

1. Age 18 years or older

2. Microbiologically confirmed pulmonary Tuberculosis, including cavitary, lymph node or military pulmonary TB

3. Asymptomatic by the end of intense phase ATT (8 weeks) and remains asymptomatic until AZA dosing.

4. Acid-Fast Bacilli (AFB)-smear negative at the end of intensive phase.

5. 1-month sputum culture negative and 2-month sputum with no growth at time of study entry.

6. HIV-negative.

7. Adequate hepatic function (direct bilirubin 1.5 x upper limit of normal (ULN) or less, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) 1.5 x ULN or less) at the end of ATT intensive phase.

8. Adequate renal function (creatinine 2 mg/dl or less and glomular filtration rate (GFR) 60 or greater).

9. Written informed consent obtained

10. Women and men of childbearing potential must agree to use 2 clinically effective methods of contraception (e.g., oral, intrauterine device [IUD], diaphragm plus spermicide, injectable, transdermal or implantable contraception) during the study and at least 3 months after the last treatment.

Exclusion Criteria:

1. HIV-infection

2. Pre-existing liver disease as defined by imaging or pathology consistent with moderate or worse firbrosis or cirrhosis (Metavir scoring system F2)

3. Smear-positive at 2 months

4. 1-month or 2 month sputum culture positive at time of study entry.

5. Participants with extrapulmonary TB.

6. History or current drug-resistant tuberculosis

7. After consent and within two weeks before Investigational Product (IP), a study complete blood count (CBC) will be performed and individuals with cytopenias (Hemoglobin <12 g/dL, WBC < 3 cells/ mm3, Absolute Neutrophil Count (ANC) < 2,000 cells/mm3, or platelets < 110 platelets/mm3) will be excluded.

8. Any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the patient at unacceptable risk of study treatment.

9. Pregnant or breast feeding females.

10. 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)

11. 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

12. Cancer (excluding surgically treated skin cancer) or hematologic malignancy currently active or active in the past three years.

13. Abnormal coagulation parameters (Prothrombin Time (PT) >15 seconds, Partial Thromboplastin (PTT) >40 seconds, and/or international normalized ratio (INR) >1.5)

14. Significant active cardiac disease within the previous 6 months including:

1. New York Heart Association (NYHA) class 4 congestive heart failure (CHF)

2. Unstable angina

3. Myocardial infarction

15. Active viral infection with HIV or hepatitis type B or C

16. Known or suspected hypersensitivity to azacytidine or mannitol

17. Inability to give informed consent.