TB Host Directed Therapy

NCT02968927 | Unknown Phase 2 DMC

• 1 other identifier: TBHDT-AUR1-8-178
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (1)

• SAEs and SUSARs

  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).

  through day 180

Secondary Outcomes (2)

• TEAEs other than SAEs and SUSARs

  through day 180

• Sputum culture status on day 56

  day 56

Other Outcomes (6)

• Change in FEV1 from baseline to 2 and 6 months

  days 56 and 180

• 18F-FDG PET/CT imaging (change from baseline to 2 months):

  day 56

• Serum neopterin

  day 56

Study Arms (5)

2HRbEZ/4HRb

ACTIVE COMPARATOR

2HRbZE

Drug: 2HRbZE/4HRb

Everolimus

EXPERIMENTAL

Everolimus 0.5 MG

Drug: Everolimus 0.5 MG; Drug: 2HRbZE/4HRb

Auranofin

EXPERIMENTAL

Auranofin 6 MG

Drug: Auranofin 6 MG; Drug: 2HRbZE/4HRb

Vitamin D

EXPERIMENTAL

Vitamin D3

Drug: Vitamin D3; Drug: 2HRbZE/4HRb

CC-11050

EXPERIMENTAL

CC-11050

Drug: CC-11050; Drug: 2HRbZE/4HRb

Interventions

Everolimus 0.5 MG DRUG

Everolimus

Auranofin 6 MG DRUG

Auranofin

Vitamin D3 DRUG

Vitamin D

CC-11050 DRUG

CC-11050

2HRbZE/4HRb DRUG

Also known as: rifabutin-modified TB therapy

2HRbEZ/4HRb; Auranofin; CC-11050; Everolimus; Vitamin D

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide signed written consent or witnessed oral consent in the case of illiteracy, prior to undertaking any trial-related procedures.
• 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.
• Body weight (in light clothing without shoes) between 40 and 90 kg.
• First episode of pulmonary tuberculosis diagnosed by positive sputum AFB smear with subsequent culture confirmation OR positive Xpert TB/RIF with Ct \<20 \[4\].
• RIF susceptibility diagnosed by Xpert TB/RIF OR Hain test
• Chest radiograph meeting criteria for moderate or far advanced pulmonary tuberculosis \[5\]
• HIV-1 seronegative
• HBsAg negative

You may not qualify if:

• 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
• Current or imminent treatment for malaria.
• 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.
• TB meningitis or other forms of severe tuberculosis with high risk of a poor outcome as judged by the investigator.
• History of allergy or hypersensitivity to any of the trial therapies or related substances, including known allergy or suspected hypersensitivity to rifampin or rifabutin.
• Having participated in other clinical trials with investigational agents within 8 weeks prior to trial start or currently enrolled in an investigational trial.
• Subjects with any of the following at screening:
• Cardiac arrhythmia requiring medication;
• Prolongation of QT/QTc interval with QTcF (Fridericia correction) \>450 ms;
• History of additional risk factors for Torsade de Pointes, (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
• Any clinically significant ECG abnormality, in the opinion of the investigator.
• Patients requiring concomitant medications that prolong the QT inter-val.
• 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.
• Use of systemic corticosteroids within the past 28 days.
• Subjects with any of the following abnormal laboratory values:

Sponsors & Collaborators

• The Aurum Institute NPC: lead

Study Sites (1)

The Aurum Institute: Tembisa Clinical Research Centre

Tembisa, Gauteng, 1736, South Africa

Location

Related Publications (1)

• Wallis RS, Ginindza S, Beattie T, Arjun N, Likoti M, Edward VA, Rassool M, Ahmed K, Fielding K, Ahidjo BA, Vangu MDT, Churchyard G. Adjunctive host-directed therapies for pulmonary tuberculosis: a prospective, open-label, phase 2, randomised controlled trial. Lancet Respir Med. 2021 Aug;9(8):897-908. doi: 10.1016/S2213-2600(20)30448-3. Epub 2021 Mar 16.

  PMID: 33740465 DERIVED

MeSH Terms

Conditions

Tuberculosis

Interventions

Everolimus; Auranofin; Cholecalciferol; CC-11050

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Aurothioglucose; Organogold Compounds; Organometallic Compounds; Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Robert S Wallis, MD,FIDSA

  The Aurum Institute NPC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: November 21, 2016
• Study Start: November 1, 2016
• Primary Completion: September 1, 2018
• Study Completion: December 1, 2020
• Last Updated: January 10, 2019

Record last verified: 2019-01

Locations

ZA (1)