A Trial of Stratified Patient-Centered Treatment Regimens for Active TB (SPECTRA-TB)

NCT07595042 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: A541438987
• Study Type: interventional
• Target: 900
• Locations: 16 countries
• Sites: 29

Brief Summary

The A5414 study will evaluate whether treatment for drug-susceptible pulmonary tuberculosis (TB) can be tailored according to a participant's risk of an unfavorable outcome. Participants will be assigned to lower-risk or higher-risk groups using baseline characteristics and then randomized within each group to receive either standard TB treatment or an investigational rifapentine- and moxifloxacin-containing regimen. The study will evaluate whether shorter treatment durations may be used in lower-risk participants and whether the investigational regimen may improve outcomes in higher-risk participants. Safety and tolerability will also be evaluated.

Conditions

Tuberculosis

Keywords

Tuberculosis; Pulmonary tuberculosis; Drug-susceptible tuberculosis; Rifampin-susceptible tuberculosis; Rifapentine; Moxifloxacin; HIV coinfection; Treatment shortening; Risk-stratified treatment

Outcome Measures

Primary Outcomes (2)

• Lower-risk group: Proportion of participants with sustained cure at 52 weeks after randomization

  Sustained cure is defined as: participant known to be alive at or after 52 weeks after randomization; sustained culture negativity at 52 weeks after randomization, defined as the last 2 liquid cultures collected at different visits being Mtb-negative without an intervening Mtb-positive result, with the last collected no earlier than 48 weeks after randomization; no treatment failure or relapse through 52 weeks after randomization; and no retreatment or additional TB treatment beyond assigned study treatment through 52 weeks after randomization. Participants will be classified as having presence of sustained cure, absence of sustained cure, or not assessable.

  52 weeks after randomization

• Lower-risk group: Proportion of participants with at least 1 new Grade 3 to 5 adverse event through 28 weeks after randomization

  Occurrence of at least 1 new Grade 3 to 5 adverse event during the 28 weeks following randomization among participants in the lower-risk group, where 28 weeks is 2 weeks beyond the longest scheduled treatment duration of 26 weeks.

  Baseline through 28 weeks after randomization

Secondary Outcomes (6)

• Higher-risk group: Proportion of participants with sustained cure at 52 week after randomization

  52 weeks after randomization

• Higher-risk group: Proportion of participants with at least 1 new Grade 3 to 5 adverse event through 28 weeks after randomization

  Baseline through 28 weeks after randomization

• Proportion of participants with sustained cure at 72 weeks after randomization

  72 weeks after randomization

• Cumulative proportion of stable liquid mycobacterial culture conversion by 26 weeks after randomization

  Baseline through 26 weeks after randomization

• Mean liquid mycobacterial culture log10 days to positivity slope during the first 10 weeks after randomization

  During the first 10 weeks after randomization

Study Arms (8)

Arm 1A: Higher-risk control group

ACTIVE COMPARATOR

Participants at higher risk of unfavorable outcome will receive 26 weeks of standard-of-care treatment consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by isoniazid and rifampin for 18 weeks.

Drug: Isoniazid; Drug: Rifampin; Drug: Pyrazinamide; Drug: Ethambutol

Arm 1B: Higher-risk experimental group

EXPERIMENTAL

Participants at higher risk of unfavorable outcome will receive 26 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin

Arm 2A: Lower-risk control group

ACTIVE COMPARATOR

Participants at lower risk of unfavorable outcome will receive 26 weeks of standard-of-care treatment consisting of isoniazid, rifampin, pyrazinamide, and ethambutol for 8 weeks, followed by isoniazid and rifampin for 18 weeks.

Drug: Isoniazid; Drug: Rifampin; Drug: Pyrazinamide; Drug: Ethambutol

Arm 2B: Lower-risk experimental group (10 week duration)

EXPERIMENTAL

Participants at lower risk of unfavorable outcome will receive 10 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin

Arm 2C: Lower-risk experimental group (12 week duration)

EXPERIMENTAL

Participants at lower risk of unfavorable outcome will receive 12 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin

Arm 2D: Lower-risk experimental group (14 week duration)

EXPERIMENTAL

Participants at lower risk of unfavorable outcome will receive 14 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin

Arm 2E: Lower-risk experimental group (16 week duration)

EXPERIMENTAL

Participants at lower risk of unfavorable outcome will receive 16 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin

Arm 2F: Lower-risk experimental group (18 week duration)

EXPERIMENTAL

Participants at lower risk of unfavorable outcome will receive 18 weeks of the HP1500ZM regimen consisting of rifapentine 1500 mg once daily, moxifloxacin 400 mg once daily, and isoniazid 300 mg once daily, with weight-based pyrazinamide during the first 8 weeks.

Drug: Isoniazid; Drug: Pyrazinamide; Drug: Rifapentine; Drug: Moxifloxacin

Interventions

Isoniazid DRUG

Administered orally once daily

Arm 1A: Higher-risk control group; Arm 1B: Higher-risk experimental group; Arm 2A: Lower-risk control group; Arm 2B: Lower-risk experimental group (10 week duration); Arm 2C: Lower-risk experimental group (12 week duration); Arm 2D: Lower-risk experimental group (14 week duration); Arm 2E: Lower-risk experimental group (16 week duration); Arm 2F: Lower-risk experimental group (18 week duration)

Rifampin DRUG

Administered orally once daily

Arm 1A: Higher-risk control group; Arm 2A: Lower-risk control group

Pyrazinamide DRUG

Administered orally once daily

Arm 1A: Higher-risk control group; Arm 1B: Higher-risk experimental group; Arm 2A: Lower-risk control group; Arm 2B: Lower-risk experimental group (10 week duration); Arm 2C: Lower-risk experimental group (12 week duration); Arm 2D: Lower-risk experimental group (14 week duration); Arm 2E: Lower-risk experimental group (16 week duration); Arm 2F: Lower-risk experimental group (18 week duration)

Ethambutol DRUG

Administered orally once daily

Arm 1A: Higher-risk control group; Arm 2A: Lower-risk control group

Rifapentine DRUG

Administered orally once daily

Arm 1B: Higher-risk experimental group; Arm 2B: Lower-risk experimental group (10 week duration); Arm 2C: Lower-risk experimental group (12 week duration); Arm 2D: Lower-risk experimental group (14 week duration); Arm 2E: Lower-risk experimental group (16 week duration); Arm 2F: Lower-risk experimental group (18 week duration)

Moxifloxacin DRUG

Administered orally once daily

Arm 1B: Higher-risk experimental group; Arm 2B: Lower-risk experimental group (10 week duration); Arm 2C: Lower-risk experimental group (12 week duration); Arm 2D: Lower-risk experimental group (14 week duration); Arm 2E: Lower-risk experimental group (16 week duration); Arm 2F: Lower-risk experimental group (18 week duration)

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Has pulmonary tuberculosis (TB) that is likely to respond to standard TB medicines (drug-susceptible TB), based on sputum testing done within 7 days before entering the study. The test must show Mycobacterium tuberculosis is present, with no rifamycin resistance detected and no known resistance to isoniazid or fluoroquinolones.
• Has a SPECTRA-TB risk score and risk group assigned during screening using the study-specific calculator.
• Has a Karnofsky performance score of 50 or higher within 30 days before entering the study.
• Has documented HIV-1 status (either with HIV or without HIV) based on acceptable testing.
• If living with HIV, has a CD4+ cell count of at least 50 cells/mm3 within 60 days before study entry.
• If living with HIV, is currently receiving or plans to start an efavirenz-based or dolutegravir-based antiretroviral therapy regimen by study week 8.
• Has laboratory test results within 7 days before study entry that meet all of the following:
• alanine aminotransferase (ALT) no more than 3 times the upper limit of normal
• total bilirubin no more than 2.5 times the upper limit of normal
• creatinine no more than 2 times the upper limit of normal
• potassium between 3.5 and 5.5 mEq/L
• absolute neutrophil count at least 1000/mm3
• hemoglobin at least 7.0 g/dL
• platelet count at least 100,000/mm3
• If able to become pregnant, has a negative blood or urine pregnancy test within 7 days before study entry.

You may not qualify if:

• TB bacteria are known to be resistant to 1 or more of the following medicines: rifampin, isoniazid, pyrazinamide, ethambutol, or fluoroquinolones.
• Received more than 5 days of treatment for active TB within the 24 weeks before study entry.
• Received more than 5 days of treatment within the 30 days before study entry with certain TB medicines or related antibiotics, including isoniazid, rifampin, rifapentine, ethambutol, moxifloxacin, pyrazinamide, aminoglycosides, fluoroquinolones, linezolid, bedaquiline, pretomanid, and other specified anti-TB drugs.
• Has suspected or confirmed TB involving the brain or central nervous system, bones, joints, heart lining (pericardium), or miliary TB.
• Has a past history of suspected or confirmed drug-resistant TB of any type.
• Is currently pregnant or breastfeeding.
• Cannot take medicines by mouth.
• Has an HIV/AIDS-related opportunistic infection at study entry.
• Has acute or chronic hepatitis B, unless the hepatitis B infection has cleared.
• Has acute or chronic hepatitis C, unless the hepatitis C infection has cleared or has been successfully treated.
• Has alcohol-related liver disease.
• Has liver cirrhosis.
• Has a history of aortic aneurysm or aortic dissection.
• Has a known history of long QT syndrome, a first-degree relative with long QT syndrome, or a screening ECG showing QTcF greater than 470 ms that does not correct with treatment of contributing factors.
• Is taking other medicines that can prolong the QT interval and cannot safely switch to an alternative medicine.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• ViiV Healthcare: collaborator

Study Sites (29)

Fundacion Huesped CRS (Site # 31957)

Buenos Aires, Argentina

Location

Vietnam-University of Sydney CRS (Site # 32495)

Sydney, Australia

Location

Gaborone CRS (Site #: 12701)

Gaborone, Botswana

Location

Molepolole CRS (Site # 12702)

Gaborone, Botswana

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS (Site #: 12101)

Rio de Janeiro, 21040-360, Brazil

Location

Instituto de Pesquisas em AIDS do Rio Grande do Sul - IPARGS CRS (Site # 12201)

Rio Grande, Brazil

Location

GHESKIO Institute of Infectious Diseases and Reproductive Health (GHESKIO - IMIS) CRS (Site #: 31730)

Port-au-Prince, HT-6110, Haiti

Location

Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS (Site #: 30022)

Port-au-Prince, HT-6110, Haiti

Location

Byramjee Jeejeebhoy Government Medical College (BJGMC) CRS (Site #: 31441)

Pune, Maharashtra, 411001, India

Location

YRG CARE CRS (Site # 32075)

Chennai, India

Location

Moi University Clinical Research Center (MUCRC) CRS (Site #: 12601)

Eldoret, Rift Valley, 30100, Kenya

Location

Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP) CRS (Site #: 12501)

Kericho, Rift Valley, 20200, Kenya

Location

Malawi CRS (Site #: 12001)

Lilongwe, Central Region, Malawi

Location

Blantyre CRS (Site #: 30301)

Blantyre, Malawi

Location

Nutrición-Mexico CRS (Site #: 32078)

Mexico City, 14000, Mexico

Location

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC) (Site # 31970)

Callao, Peru

Location

Barranco CRS (Site #: 11301)

Lima, Peru

Location

San Miguel CRS (Site # 11302)

Lima, Peru

Location

Socios en Salud Sucursal Peru CRS (Site # 31985)

Lima, Peru

Location

TB HIV Innovations and Clinical Research Foundation Corp. (Site #: 31981)

Dasmariñas, Cavite, 4114, Philippines

Location

Kilimanjaro Christian Medical Centre (KCMC) (Site # 5118)

Moshi, Tanzania

Location

Thai Red Cross AIDS Research Centre (TRC-ARC) CRS (Site #: 31802)

Pathum Wan, Bangkok, 10330, Thailand

Location

Siriraj Hospital, Mahidol University NICHD CRS (Site # 5115)

Bangkok, Thailand

Location

Chiang Mai University HIV Treatment (CMU HIV Treatment) CRS (Site #: 31784)

Chiang Mai, 50200, Thailand

Location

Chiangrai Prachanukroh Hospital NICHD CRS (Site # 5116)

Chiang Rai, Thailand

Location

Joint Clinical Research Centre (JCRC)/Kampala Clinical Research Site (Site #: 12401)

Kampala, 10005, Uganda

Location

MU-JHU Research Collaboration (MUJHU CARE LTD) CRS (Site # 30293)

Kampala, Uganda

Location

National Lung Hospital (Site #: 32483)

Hanoi, 100000, Vietnam

Location

Milton Park CRS (Site #: 30313)

Harare, 263663, Zimbabwe

Location

MeSH Terms

Conditions

Tuberculosis; Tuberculosis, Pulmonary; HIV Infections

Interventions

Isoniazid; Rifampin; Pyrazinamide; Ethambutol; rifapentine; Moxifloxacin

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydrazines; Organic Chemicals; Isonicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Pyrazines; Ethylenediamines; Diamines; Polyamines; Amines; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring

Study Officials

• Gustavo Velásquez, MD, MPH

  University of California, San Francisco

  STUDY CHAIR

• Patrick Phillips, PhD

  San Francisco General Hospital

  STUDY CHAIR

• Susan Dorman, MD

  Medical University of South Carolina

  STUDY CHAIR

Central Study Contacts

Gustavo Velásquez, MD, MPH

CONTACT

628-206-2400; gustavo.velasquez@ucsf.edu

Study Design

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

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 19, 2026
• Study Start (Estimated): June 5, 2026
• Primary Completion (Estimated): June 5, 2029
• Study Completion (Estimated): October 22, 2029
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the ACTG (Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections) by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the ACTG. * For what types of analyses? To achieve aims in the proposal approved by the ACTG. * By what mechanism will data be made available? Researchers may submit a request for access to data using the ACTG "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

Locations

ME (1); HA (2); PH (1); VN (1); BO (2); TH (4); AR (1); IN (2); KE (2); PE (4); TA (1); UG (2); AU (1); MA (2); ZI (1); BR (2)