A randomized controlled trial of two adjunctive host-directed therapies in rifampin-resistant tuberculosis (DRTB-HDT).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

The Aurum Institute, Quality Regulatory Clinical Ireland Limited, Quality Regulatory Clinical Ireland Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

completed 30 Nov 2025

Decision date (initial)

2025-01-30

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Horizon 2020 Programme European Commission

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Therapy, Pharmacodynamic, Efficacy

To investigate the safety, tolerability and preliminary efficacy of two therapies adjuvants (one anti-inflammatory and one antimicrobial) in patients with pulmonary tuberculosis resistant to Rifampicin. Efficacy objectives will include treatment and pulmonary function recovery measures, as well as eradication of M tuberculosis infection.
Co-Primary Objectives:
1. VEMS la luna 6
2. Probability of stable crop conversion by month 6
Both co-primary objectives must be met for a treatment to be considered successful. The CC11050 and metforminium arms will each be compared to the control arm

Secondary objectives 1

1. 1. FEVs and FVC at additional times (2, 6 and 18 months) 2. FEVs and FVC evolution over time 3. Proportion of patients with negative sputum cultures after 2 and 6 months of treatment 4. Proportion of patients with new TB drug resistance The proportion of patients whose treatment is considered unsuccessful due to failure, relapse or death, individually and totally

Conditions and MedDRA coding

Multidrug rezistant pulmonary tuberculosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Between the ages of 16 and 65 2. Able and willing to provide signed written consent, or verbal consent of witnesses in case of illiteracy, before undertaking any process-related procedures. In the case of children aged 16 or 17 years, consent of at least one parent or guardian plus consent of the child will be required. 3. Body weight (in light clothing without shoes) between 30 and 90 kg. 4. Positive sputum Xpert (TB/RIF or Ultra) with Ct ≤22, with subsequent culture confirmation. 5. RIF resistance diagnosed by Xpert OR Hain test OR phenotypic drug susceptibility testing 6. Chest radiograph meeting National TB Association criteria for moderate or very advanced pulmonary tuberculosis 7. If sexually active, willing to use an effective contraceptive method during TB treatment 8. HIV-1 seronegative, OR if HIV-1 seropositive, presenting to an African study site with a CD4 T-cell count > 100/μl and either currently receiving ART or willing to start ART during study participation, as specified NB: HIV+ patients will only be enrolled in African sites

Exclusion criteria 1

1. 1. Any condition for which participation in the trial, as judged by the investigator, could compromise the subject's well-being or prevent, limit, or confound protocol-specified assessments 2. Current or imminent treatment (within 24 hours) for malaria. 3. Pregnancy or breastfeeding 4. Severely ill, such that, in the opinion of the investigator, death is likely during the trial. 5. TB meningitis or other forms of severe TB with increased risk of poor outcome as judged by the investigator. 6. History of allergy or hypersensitivity to any of the study therapies or related substances. 7. Have participated in other clinical trials with investigational agents within 8 weeks prior to study initiation or currently enrolled in an investigational trial. 8. Previous RIF‐R‐TB treatment within the past 12 months 9. Cardiac arrhythmia requiring medication or any clinically significant ECG abnormality, in the opinion of the investigator 10. Requires treatment with drugs that are strong inducers or inhibitors of CYP3A4 (e.g., ketoconazole, lopinavir, or cobicistat), carbonic anhydrase inhibitors (e.g., acetazolamide), or OCT2 or MATE inhibitors (e.g., cimetidine, pyrimethamine). 11. Use of systemic corticosteroids within the past 28 days. 12. History of unstable diabetes mellitus requiring hospitalization for hyper‐ or hypoglycemia within the past year prior to screening or requiring treatment with metformin. 13. Subjects with any of the following abnormal laboratory values: A. creatinine >2 mg/dl b. hemoglobin <8 g/dL/ . c. platelets <100x109 cells/L d. serum potassium <3.5 e. alanine aminotransferase (ALT) ≥2.0 x ULN f. alkaline phosphatase (AP) >5.0 x ULN g. total bilirubin >1.5 mg/dL h. Hepatitis B surface antigen positive i. random blood glucose >140 mg/dL (7.8 mmol/L) j. SARS-CoV-2 PCR or antigen test positive NB: All inclusion criteria and none of the exclusion criteria must be met. NB: Enrolled patients whose initial sputum cultures subsequently fail to demonstrate RIF-R-TB growth will be excluded from the mITT and PP populations. They may be excluded from further study participation based on the individual benefit-risk ratio, as assessed by the study site, PI and DMC.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To examine the safety, tolerability, and preliminary efficacy of two adjuvant TB-HDT therapies (one anti-inflammatory and one antimicrobial) in patients with rifampicin-resistant pulmonary tuberculosis. Efficacy endpoints will include measures of lung function recovery and eradication of M tuberculosis infection. Time point of assessment for this primary endpoint: month 6 (nominal months of 4 weeks)

Secondary endpoints 1

1. 1. FEV1 at month 6 2. Probability of stable culture conversion by month 6 Both co-primary endpoints must be met for a treatment to be considered successful. The CC-11050 and Metformin arms will each be compared to the control arm. Time of assessment of this secondary endpoint: Up to 18 months after study entry.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

The Aurum Institute

Sponsor organisation

The Aurum Institute

Address

29 Queens Road, Parktown Parktown

City

Johannesburg

Postcode

2193

Country

South Africa

Scientific contact point

Organisation

Quality Regulatory Clinical Ireland Limited

Contact name

Sarah Fryer

Public contact point

Organisation

Quality Regulatory Clinical Ireland Limited

Contact name

Sarah Fryer

Third parties 1

Quality Regulatory Clinical Ireland Limited

Sponsor organisation

Quality Regulatory Clinical Ireland Limited

Address

21 Priory Office Park, Stillorgan Road Stillorgan Road

City

Blackrock

Postcode

A94 F660

Country

Ireland

Scientific contact point

Organisation

Quality Regulatory Clinical Ireland Limited

Contact name

Sarah Fryer

Quality Regulatory Clinical Ireland Limited

Sponsor organisation

Quality Regulatory Clinical Ireland Limited

Address

21 Priory Office Park, Stillorgan Road Stillorgan Road

City

Blackrock

Postcode

A94 F660

Country

Ireland

Scientific contact point

Organisation

Quality Regulatory Clinical Ireland Limited

Contact name

Sarah Fryer

Sponsor responsibilities

Article 77 implementation

The Aurum Institute

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications