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Trial record 2 of 12 for:    AURUM 8

TB Host Directed Therapy (TBHDT)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2016 by The Aurum Institute NPC
Sponsor:
Information provided by (Responsible Party):
The Aurum Institute NPC
ClinicalTrials.gov Identifier:
NCT02968927
First received: September 8, 2016
Last updated: November 17, 2016
Last verified: November 2016
  Purpose
To examine the safety and preliminary efficacy of multiple adjunctive host directed TB therapies (TB HDT), to assess their potential to shorten TB treatment and/or prevent permanent lung damage.

Condition Intervention Phase
Tuberculosis
Drug: Everolimus 0.5 MG
Drug: Auranofin 6 MG
Drug: Vitamin D3
Drug: CC-11050
Drug: 2HRbZE/4HRb
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Ph2 Randomized Trial to Evaluate the Safety Preliminary Efficacy and Biomarker Response of Host Directed Therapies Added to Rifabutin-modified Standard Therapy in Adults With Drug-Sensitive Smear-Positive Pulmonary TB

Resource links provided by NLM:


Further study details as provided by The Aurum Institute NPC:

Primary Outcome Measures:
  • SAEs and SUSARs [ Time Frame: through day 180 ] [ Designated as safety issue: Yes ]

    For auranofin, everolimus, and vitamin D: the proportions of patients experiencing suspected unexpected serious adverse reactions (SUSARs).

    For CC-11050: the proportion of patients experiencing treatment emergent serious adverse events (SAEs).



Secondary Outcome Measures:
  • TEAEs other than SAEs and SUSARs [ Time Frame: through day 180 ] [ Designated as safety issue: Yes ]
    TEAEs other than SAEs, categorized according to severity, drug relatedness, and leading to early withdrawal.

  • Sputum culture status on day 56 [ Time Frame: day 56 ] [ Designated as safety issue: Yes ]
    Proportion of patients with positive sputum cultures on solid culture medium after 8 weeks of treatment


Other Outcome Measures:
  • Change in FEV1 from baseline to 2 and 6 months [ Time Frame: days 56 and 180 ] [ Designated as safety issue: No ]
    FEV1 (% of expected value)

  • 18F-FDG PET/CT imaging (change from baseline to 2 months): [ Time Frame: day 56 ] [ Designated as safety issue: No ]
    Maximum and mean standardized uptake values (SUV)

  • Serum neopterin [ Time Frame: day 56 ] [ Designated as safety issue: No ]
    change from baseline b. CRP

  • Quantiferon gold in tube [ Time Frame: day 56 ] [ Designated as safety issue: No ]
    change from baseline

  • Gene expression profiles (exploratory) [ Time Frame: days 56 and 180 ] [ Designated as safety issue: No ]
    Change from baseline to 2 and 6 months in gene expression profiles

  • PD-1 expression (exploratory) [ Time Frame: days 56 and 180 ] [ Designated as safety issue: No ]
    PD-1 expression on CD4 and CD8 lymphocytes


Estimated Enrollment: 200
Study Start Date: November 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 2HRbEZ/4HRb
2HRbZE
Drug: 2HRbZE/4HRb
Other Name: rifabutin-modified TB therapy
Experimental: Everolimus
Everolimus 0.5 MG
Drug: Everolimus 0.5 MG Drug: 2HRbZE/4HRb
Other Name: rifabutin-modified TB therapy
Experimental: Auranofin
Auranofin 6 MG
Drug: Auranofin 6 MG Drug: 2HRbZE/4HRb
Other Name: rifabutin-modified TB therapy
Experimental: Vitamin D
Vitamin D3
Drug: Vitamin D3 Drug: 2HRbZE/4HRb
Other Name: rifabutin-modified TB therapy
Experimental: CC-11050
CC-11050
Drug: CC-11050 Drug: 2HRbZE/4HRb
Other Name: rifabutin-modified TB therapy

Detailed Description:

OBJECTIVES:

To determine the safety and preliminary efficacy of 4 TB HDT candidates:

  1. Safety (treatment emergent serious adverse events and SUSARs)
  2. Microbiologic effects in sputum (culture conversion, change in MGIT TTP) and blood (WBA)
  3. PET/CT imaging
  4. Serum markers of inflammation
  5. Effects on Mtb-specific and general immune function
  6. Pulmonary effects (spirometry, 6MWT, O2 saturation, and St. George Respiratory Symptom Questionnaire) In each case, TB HDT effects will be determined by comparison to patients treated with standard TB therapy alone with regard to a common set of primary and secondary endpoints.

PRIMARY ENDPOINTS

  1. For auranofin, everolimus, and vitamin D: the proportions of patients experiencing suspected unexpected serious adverse reactions (SUSARs).
  2. For CC-11050: the proportion of patients experiencing treatment emergent serious adverse events (SAEs).
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Willing and able to provide signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.
  2. Aged 18 to 65 years, male, or if female, either not of reproductive potential (post-menopause, or status-post surgical sterilization) or with an intrauterine contraceptive device in place.
  3. Body weight (in light clothing without shoes) between 40 and 90 kg.
  4. First episode of pulmonary tuberculosis diagnosed by positive sputum AFB smear with subsequent culture confirmation OR positive Xpert TB/RIF with Ct <20 [4].
  5. RIF susceptibility diagnosed by Xpert TB/RIF OR Hain test
  6. Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis [5]
  7. HIV-1 seronegative
  8. HBsAg negative

Exclusion Criteria:

  1. Any condition for which participation in the trial, as judged by the investigator, could compromise the well-being of the subject or prevent, limit or confound protocol specified assessments
  2. Current or imminent treatment for malaria.
  3. Is critically ill, and in the judgment of the investigator has a diagnosis likely to result in death during the trial or the follow-up period.
  4. TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
  5. History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin or rifabutin.
  6. Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
  7. Subjects with any of the following at screening:

    1. Cardiac arrhythmia requiring medication;
    2. Prolongation of QT/QTc interval with QTcF (Fridericia correction) >450 ms;
    3. History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
    4. Any clinically significant ECG abnormality, in the opinion of the investigator.
    5. Patients requiring concomitant medications that prolong the QT inter-val.
  8. Random blood glucose >140 mg/dL, or history of unstable Diabetes Mellitus which required hospitalization for hyper- or hypoglycaemia within the past year prior to start of screening.
  9. Use of systemic corticosteroids within the past 28 days.
  10. Subjects with any of the following abnormal laboratory values:

    1. creatinine >2 mg/dL
    2. haemoglobin <8 g/dL
    3. platelets <100x109 cells/L
    4. serum potassium <3.5
    5. aspartate aminotransferase (AST) ≥2.0 x ULN
    6. alkaline phosphatase (AP) >5.0 x ULN
    7. total bilirubin >1.5 mg/dL
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02968927

Contacts
Contact: Trevor Ryan Beattie, BSc, BSc(Hons) +27 10 590 1319 tbeattie@auruminstitute.org
Contact: René Wills +27 10 590 1399 rwills@auruminstitute.org

Sponsors and Collaborators
The Aurum Institute NPC
Investigators
Principal Investigator: Robert S Wallis, MD,FIDSA The Aurum Instityute, NPC
  More Information

Responsible Party: The Aurum Institute NPC
ClinicalTrials.gov Identifier: NCT02968927     History of Changes
Other Study ID Numbers: TBHDT-AUR1-8-178 
Study First Received: September 8, 2016
Last Updated: November 17, 2016
Health Authority: South Africa: Medicines Control Council
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Everolimus
Sirolimus
Rifabutin
Auranofin
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antirheumatic Agents
Antibiotics, Antitubercular
Antitubercular Agents

ClinicalTrials.gov processed this record on December 07, 2016