Candidate Clinical Correlate of Prognostic Outcome for TB Study

NCT07018076 | Recruiting FDA Device

• 1 other identifier: U01AI152087-05S1
• Study Type: observational
• Target: 750
• Locations: 2 countries
• Sites: 3

Brief Summary

As part of the ongoing efforts within the Rapid Research in Diagnostics Development for TB Network (R2D2 TB Network) study, the Candidate Clinical Correlate as Prognostic Outcome for TB (C3PO) study serves as a supplement aimed at evaluating predictors and novel biomarkers of recurrent TB among TB survivors. Current tools for predicting TB recurrence risk are suboptimal, limiting the ability to assess new TB treatment regimens effectively. Identifying accurate sputum- or blood-based biomarkers for recurrence risk could significantly improve the efficiency and informativeness of Phase 2 and 3 clinical trials.

Conditions

Tuberculosis

Keywords

Tuberculosis; Global Health; Diagnostics

Outcome Measures

Primary Outcomes (2)

• Recurrent tuberculosis (TB)

  Recurrent tuberculosis (TB), defined as a new episode of microbiologically confirmed TB occurring after completion of treatment for a prior drug-sensitive TB episode. Recurrence will be identified through routine study visits during the one year follow-up, with microbiological confirmation based on sputum mycobacterial culture.

  1 year

• Prognostic accuracy of novel biomarkers in predicting recurrent TB

  We will evaluate the ability of selected novel biomarkers to predict recurrent TB using the following metrics: Area Under the Curve (AUC): Measures the overall discriminatory ability of the biomarkers to distinguish between individuals who will and will not experience recurrent TB. Sensitivity and Specificity: Sensitivity indicates how accurately the biomarkers identify individuals who will develop recurrent TB, while specificity reflects how well they identify those who will not. Positive Predictive Value (PPV) and Negative Predictive Value (NPV): PPV represents the proportion of individuals with a positive biomarker result who actually develop recurrent TB, while NPV reflects the proportion with a negative result who remain recurrence-free. Kappa Statistic: Assesses the agreement between predicted outcomes based on the biomarkers and the actual observed outcomes, accounting for agreement occurring by chance.

  1 year

Interventions

RS ratio DIAGNOSTIC_TEST

We will evaluate the non-culture, sputum-based assay RS ratio, which measures ongoing Mycobacterium tuberculosis activity by quantifying the abundance of precursor rRNA relative to mature rRNA (an indicator of active rRNA synthesis).

Blood-based host immune response assays DIAGNOSTIC_TEST

We will evaluate blood-based assays measuring host immune response parameters for predicting mycobacterial activity.

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of individuals receiving programmatic treatment for drug-sensitive tuberculosis (TB) at participating outpatient TB clinics in Uganda and Vietnam. Eligible participants will be selected from among TB patients actively receiving care at these clinical sites.

You may qualify if:

• individuals age ≥ 12 years;
• have completed treatment for drug-susceptible tuberculosis with the standard 6-month regimen of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE).

You may not qualify if:

• completed treatment for drug-susceptible tuberculosis \>14 days prior to screening/enrollment;
• routinely taking any medication with anti-mycobacterial activity (including fluoroquinolones) for any reason not related to tuberculosis treatment within the last 14 days;
• unwilling to provide informed consent or return for study follow-up visits.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of California, Irvine: collaborator
• University of Colorado, Denver: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (3)

Kisenyi Health Center

Kampala, Uganda

RECRUITING

Mulago Outpatient Department

Kampala, Uganda

RECRUITING

Hanoi Lung Hospital, Outpatient departments

Hanoi, Vietnam

NOT YET RECRUITING

Related Publications (23)

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• Kurbatova EV, Phillips PPJ, Dorman SE, Sizemore EE, Bryant KE, Purfield AE, Ricaldi J, Brown NE, Johnson JL, Wallis CL, Akol JP, Ocheretina O, Van Hung N, Mayanja-Kizza H, Lourens M, Dawson R, Nhung NV, Pierre S, Musodza Y, Shenje J, Badal-Faesen S, Vilbrun SC, Waja Z, Peddareddy L, Scott NA, Yuan Y, Goldberg SV, Swindells S, Chaisson RE, Nahid P. A Standardized Approach for Collection of Objective Data to Support Outcome Determination for Late-Phase Tuberculosis Clinical Trials. Am J Respir Crit Care Med. 2023 May 15;207(10):1376-1382. doi: 10.1164/rccm.202206-1118OC.

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  PMID: 20510279 BACKGROUND

• Imperial MZ, Phillips PPJ, Nahid P, Savic RM. Precision-Enhancing Risk Stratification Tools for Selecting Optimal Treatment Durations in Tuberculosis Clinical Trials. Am J Respir Crit Care Med. 2021 Nov 1;204(9):1086-1096. doi: 10.1164/rccm.202101-0117OC.

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• Gupta-Wright A, den Boon S, MacLean EL, Cirillo D, Cobelens F, Gillespie SH, Kohli M, Ruhwald M, Savic R, Brigden G, Gidado M, Goletti D, Hanna D, Hasan R, Hewison C, Koura KG, Lienhardt C, Lungu P, McHugh TD, McKenna L, Scott C, Scriba T, Sekaggya-Wiltshire C, Kasaeva T, Zignol M, Denkinger CM, Falzon D. Target product profiles: tests for tuberculosis treatment monitoring and optimization. Bull World Health Organ. 2023 Nov 1;101(11):730-737. doi: 10.2471/BLT.23.290901. Epub 2023 Oct 4.

  PMID: 37961060 BACKGROUND

• FDA-NIH Biomarker Working Group. BEST (Biomarkers, EndpointS, and other Tools) Resource [Internet]. Silver Spring (MD): Food and Drug Administration (US); 2016-. Available from http://www.ncbi.nlm.nih.gov/books/NBK326791/

  PMID: 27010052 BACKGROUND

• MacLean EL, Zimmer AJ, den Boon S, Gupta-Wright A, Cirillo DM, Cobelens F, Gillespie SH, Nahid P, Phillips PP, Ruhwald M, Denkinger CM. Tuberculosis treatment monitoring tests during routine practice: study design guidance. Clin Microbiol Infect. 2024 Apr;30(4):481-488. doi: 10.1016/j.cmi.2023.12.027. Epub 2024 Jan 3.

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• Dorman SE, Nahid P, Kurbatova EV, Phillips PPJ, Bryant K, Dooley KE, Engle M, Goldberg SV, Phan HTT, Hakim J, Johnson JL, Lourens M, Martinson NA, Muzanyi G, Narunsky K, Nerette S, Nguyen NV, Pham TH, Pierre S, Purfield AE, Samaneka W, Savic RM, Sanne I, Scott NA, Shenje J, Sizemore E, Vernon A, Waja Z, Weiner M, Swindells S, Chaisson RE; AIDS Clinical Trials Group; Tuberculosis Trials Consortium. Four-Month Rifapentine Regimens with or without Moxifloxacin for Tuberculosis. N Engl J Med. 2021 May 6;384(18):1705-1718. doi: 10.1056/NEJMoa2033400.

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• Gillespie SH, Crook AM, McHugh TD, Mendel CM, Meredith SK, Murray SR, Pappas F, Phillips PP, Nunn AJ; REMoxTB Consortium. Four-month moxifloxacin-based regimens for drug-sensitive tuberculosis. N Engl J Med. 2014 Oct 23;371(17):1577-87. doi: 10.1056/NEJMoa1407426. Epub 2014 Sep 7.

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• Nahid P, Dorman SE, Alipanah N, Barry PM, Brozek JL, Cattamanchi A, Chaisson LH, Chaisson RE, Daley CL, Grzemska M, Higashi JM, Ho CS, Hopewell PC, Keshavjee SA, Lienhardt C, Menzies R, Merrifield C, Narita M, O'Brien R, Peloquin CA, Raftery A, Saukkonen J, Schaaf HS, Sotgiu G, Starke JR, Migliori GB, Vernon A. Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016 Oct 1;63(7):e147-e195. doi: 10.1093/cid/ciw376. Epub 2016 Aug 10.

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• Dooley KE, Phillips PP, Nahid P, Hoelscher M. Challenges in the clinical assessment of novel tuberculosis drugs. Adv Drug Deliv Rev. 2016 Jul 1;102:116-22. doi: 10.1016/j.addr.2016.01.014. Epub 2016 Jan 28.

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• Dide-Agossou C, Bauman AA, Ramey ME, Rossmassler K, Al Mubarak R, Pauly S, Voskuil MI, Garcia-Cremades M, Savic RM, Nahid P, Moore CM, Tasneen R, Nuermberger EL, Robertson GT, Walter ND. Combination of Mycobacterium tuberculosis RS Ratio and CFU Improves the Ability of Murine Efficacy Experiments to Distinguish between Drug Treatments. Antimicrob Agents Chemother. 2022 Apr 19;66(4):e0231021. doi: 10.1128/aac.02310-21. Epub 2022 Mar 21.

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Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

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

Study Officials

• Adithya Cattamanchi, MD

  University of California San Francisco; University of California Irvine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adithya Cattamanchi, MD

CONTACT

415-206-5489; adithya.cattamanchi@ucsf.edu

Sophie Huddart, PhD

CONTACT

Sophie.Huddart@ucsf.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2025
• First Posted: June 12, 2025
• Study Start: November 25, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

UG (2); VN (1)