Clofazimine- and Rifapentine-Containing Treatment Shorten... | NCT04311502

NCT04311502

ID	Type	Description	Link
30148	Registry Identifier	DAIDS-ES Registry Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

This study compared a 3-month rifapentine (RPT)/clofazimine (CFZ)-containing regimen with a CFZ loading dose with the 6-month standard of care (SOC) for drug-susceptible (DS) tuberculosis (TB).

Randomization was stratified based on HIV status and the presence of advanced disease as determined by chest X-ray.

Participants were randomized to one of three arms:

Arm 1 (Experimental): rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + CFZ 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks
Arm 2 (SOC): rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks
Arm C (PK-only subgroup): PHZE + CFZ 100 mg once daily for 4 weeks; then remain on study, off study medications and treated according to SOC (RHZE for 4 weeks; then RH for 18 weeks)

All participants received pyridoxine (vitamin B6) with each dose of isoniazid (INH) based on current local, national or international dosing guidelines.

Arm 1 participants were treated for 13 weeks (including a 2-week CFZ loading dose of 300 mg daily). Arm 2 participants were treated for 26 weeks, and Arm C participants were treated for 4 weeks.

All participants in Arms 1, 2, and C were followed from randomization to Week 65.

On June 1, 2023, the Data and Safety Monitoring Board (DSMB) recommended that the study permanently close to accrual because of the high rate of treatment failure and TB recurrence. The A5362 team, NIAID and DAIDS leadership, and ACTG leadership concurred with the DSMB's recommendation and the study was closed to accrual on June 2, 2023. A letter of amendment was created that extended follow-up to 117 weeks for some participants in Arm 1.

Due to the early close to accrual, a primary analysis report forming the basis of the primary trial manuscript used data collected at study visits up to and including the date when the last enrolled participant completed the week 26 study visit (September 25. 2023). Another final analysis was performed using data collected at study visits up to the date when the last enrolled participant completed the week 65 assessment.

Study visits included physical examinations; blood, urine, and/or sputum collection; chest X-rays; and electrocardiograms (ECG).

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm 1: Experimental	Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks.	Drug: Rifapentine Drug: Isoniazid Drug: Pyrazinamide Drug: Ethambutol Drug: Clofazimine loading dose
Arm 2: Standard of care	Active Comparator	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks.	Drug: Rifampicin Drug: Isoniazid Drug: Pyrazinamide Drug: Ethambutol
Arm C: PK only subgroup	Experimental	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks).	Drug: Rifapentine Drug: Isoniazid Drug: Pyrazinamide Drug: Ethambutol Drug: Clofazimine 100 MG

Name	Type	Description	Arm Group Labels	Other Names
Rifapentine	Drug	1200 mg once daily	Arm 1: Experimental Arm C: PK only subgroup

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Time to 12 Weeks Stable Culture Conversion in Liquid Media	The time of stable culture conversion was the visit corresponding to the first of two consecutive negative cultures without an intervening positive, and/or visits wherein the participant was unable to produce sputum and had no signs of active TB. If a participant did not culture convert, they were censored at their last culture result (regardless of result). If a participant died before conversion they were censored at 12 weeks. Participants who were lost to follow-up prior to 12 weeks with their last culture being positive were censored at 12 weeks (i.e. assumed they did not have a culture conversion by week 12), and participants who were lost to follow-up prior to 12 weeks with their last culture being negative were censored at the last sampling visit for which they had a valid culture result.	From Entry through Week 12
Participants Experiencing Any Grade 3 or Higher Adverse Event (AE) That is at Least a One Grade Increase From Baseline Over 65 Weeks	An adverse event is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution. Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1, Corrected Version 2.1, July 2017) The primary manuscript outcome measure includes data through week 65 up to September 25, 2023	From entry through Week 65

Secondary Outcomes

Measure	Description	Time Frame
Proportion of Participants With Favorable Clinical/Bacteriologic Outcome (Definition A) at 65 Weeks Post-randomization	Favorable Outcome are: liquid culture negative at week 65 without signs or symptoms of ongoing active TB and unable to produce sputum at 65 weeks who at the end of the follow-up period are clinically without signs/symptoms of ongoing active TB and produce a sputum specimen that is contaminated in two liquid cultures without evidence of TB Unfavorable: Absence of cure: Having a sputum sample at or after EOT that is culture-positive (any medium) with a second positive sample obtained 4 hours following the first sample. Death from any cause except for violent or accidental cause Had a positive culture for Mtb when last seen Had a treatment extension beyond nominal level due to clinically inadequate response Unevaluable are: lost to follow-up during treatment or post-treatment with their last culture being negative for Mtb violent or accidental death becoming pregnant during their assigned active treatment and stop their assigned treatment.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Pulmonary TB (among participants with or without history of prior TB treatment) identified within 5 days prior to entry by:
- At least one sputum specimen positive for M. tuberculosis by molecular TB assay (Xpert) or line probe assay [LPA]) OR
- At least one sputum specimen positive (1+ or greater) for acid-fast bacilli (AFB) on smear microscopy
- Note: TB diagnosis for purposes of meeting inclusion criterion can be from a study testing laboratory or from an outside laboratory, as long as it is from a sputum sample collected within 5 days prior to entry.
Pulmonary TB diagnosed without known INH resistance (e.g., by LPA or Xpert) and without known RIF resistance (e.g., by either LPA or Xpert).
Absence of HIV-1 infection, as documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit, within 30 days prior to entry OR HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 E/CIA test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV-1 infection.
For participants living with HIV, CD4+ cell count ≥100 cells/mm^3, obtained within 30 days prior to study entry at any network-approved non-US laboratory that is Immunology Quality Assessment (IQA) certified.
For participants living with HIV must be currently receiving or planning to initiate antiretroviral therapy (ART) at or before study week 8.
A verifiable address or residence readily accessible to facilitate directly observed therapy (DOT), and willingness to inform the study team of any change of address during the treatment and follow-up period.
The following laboratory values obtained at or within 5 days prior to entry by any US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practice (GCLP) and participates in appropriate external quality assurance programs.
- Serum or plasma alanine aminotransferase (ALT) ≤3 times the upper limit of normal (ULN)
- Serum or plasma total bilirubin ≤2.5 times ULN
- Serum or plasma creatinine ≤2 times ULN
- Serum or plasma potassium ≥3.5 mEq/L and ≤5.5 mEq/L
- Absolute neutrophil count (ANC) ≥650/mm^3
- Hemoglobin ≥7.0 g/dL
- Platelet count ≥50,000/mm^3
For females of reproductive potential, negative serum or urine pregnancy test within 5 days prior to entry by any US clinic or laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or is using a point of care (POC)/CLIA-waived test, or at any network-approved non-US laboratory or clinic that operates in accordance with Good Clinical Laboratory Practice (GCLP) and participates in appropriate external quality assurance programs.
Female participants of reproductive potential must agree not to participate in the conception process (i.e., active attempt to become pregnant, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable nonhormonal method of contraception, as listed below, while on study treatment and for 30 days after stopping study medications.
- Acceptable forms of contraception include:
- Condoms
- Intrauterine device or intrauterine system
- Cervical cap with spermicide
- Diaphragm with spermicide
- Note: Hormonal birth control alone is not acceptable, as it may not be sufficiently reliable in combination with RPT or RIF.
Female participants who are not of reproductive potential must have documentation of menopause (i.e., at least 1 year amenorrheic), hysterectomy, or bilateral oophorectomy or bilateral tubal ligation.
Documentation of Karnofsky performance score ≥50 within 30 days prior to entry.
Documentation of either the presence or absence of advanced disease as determined by chest X-ray within 5 days prior to entry.
Ability and willingness of participant to provide informed consent.

Exclusion Criteria:

More than 5 days of treatment directed against active TB for the current TB episode preceding study entry.
Pregnant or breast-feeding.
Unable to take oral medications.
Current receipt of clofazimine or bedaquiline or known receipt of clofazamine or bedaquiline at any time in the past.
Corrected QT based on the Fridericia correction method (QTcF) interval >450 ms for men or >470 ms for women within 30 days prior to entry.
Weight <30 kg.
Current or planned use within 6 months following enrollment of one or more of the following medications: HIV protease inhibitors, HIV entry and fusion inhibitors, HIV non-nucleoside reverse transcriptase inhibitors (other than EFV), elvitegravir/cobicistat, bictegravir, quinidine, procainamide, amiodarone, sotalol, disopyramide, ziprasidone, or terfenadine.
Current extrapulmonary TB, in the opinion of the site investigator.
Current or history of known personal or family long QT syndrome.
Known allergy/sensitivity or any hypersensitivity to components of study TB drugs or their formulation.
Active drug, alcohol use or dependence; or mental illness (e.g., major depression) that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Known history of acute intermittent porphyria.
Other medical conditions (e.g., severe uncontrolled diabetes, liver or kidney disease, blood disorders, peripheral neuritis, chronic diarrhea) in which the current clinical condition of the participant is likely to prejudice the response to, or assessment of, treatment.

Contacts/Locations Module

Name	Affiliation	Role
John Metcalfe, MD, PhD, MPH	University of California, San Francisco	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS		Port-au-Prince		HT-6110	Haiti
Byramjee Jeejeebhoy Medical College (BJMC) CRS

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41510291	Derived	Mugodhi F, Kanyama C, Makiya F, Metcalfe J, Potani C, Scarsi KK, Weir I, Furin J. "Six months is a lot of time to lie": Anticipated stigma, disclosure and treatment preferences among participants in a tuberculosis therapeutic trial. Res Sq [Preprint]. 2025 Dec 22:rs.3.rs-8277920. doi: 10.21203/rs.3.rs-8277920/v1.
40915311	Derived

Label	URL
DAIDS AE Grading Table	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_ICF	Yes	No	Yes	Study Protocol and Informed Consent Form: Protocol Version 2.0	Jul 8, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

Masking Info

FG00058 subjects
FG00131 subjects
FG00215 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
BG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg
BG002	Arm C: PK Only Subgroup	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks). Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine: (CFZ) 100 mg once daily
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Inter-Quartile Range

years

Title

Denominators

Categories

Title	Measurements
	BG00033(27 to 39) BG00130(24 to 38) BG00235(31 to 43) BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00011 BG0019 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

ASIAN

Title	Measurements
	BG0009 BG0016 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

Haiti

Title	Measurements
	BG0002 BG0012 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Time to 12 Weeks Stable Culture Conversion in Liquid Media

The time of stable culture conversion was the visit corresponding to the first of two consecutive negative cultures without an intervening positive, and/or visits wherein the participant was unable to produce sputum and had no signs of active TB.

If a participant did not culture convert, they were censored at their last culture result (regardless of result). If a participant died before conversion they were censored at 12 weeks. Participants who were lost to follow-up prior to 12 weeks with their last culture being positive were censored at 12 weeks (i.e. assumed they did not have a culture conversion by week 12), and participants who were lost to follow-up prior to 12 weeks with their last culture being negative were censored at the last sampling visit for which they had a valid culture result.

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Median

Inter-Quartile Range

weeks

From Entry through Week 12

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Units	Counts
Participants	OG00055 OG00131

Title

Denominators

Categories

Title	Measurements
	OG0006(4 to 8) OG0018(6 to 10)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	This comparison is adjusting for HIV-1 status (positive/negative) and TB Disease at Screening (Advanced/Not Advanced).	Regression, Cox	Adjusted for HIV-1 status (positive/negative) and TB Disease at Screening (Advanced/Not Advanced).	0.21		Hazard Ratio (HR)	1.21			2-Sided	90	0.82	1.79			Arm 1 vs Arm 2		Superiority

Primary

Participants Experiencing Any Grade 3 or Higher Adverse Event (AE) That is at Least a One Grade Increase From Baseline Over 65 Weeks

An adverse event is any unfavorable and unintended sign, symptom, or diagnosis that occurs in a study participant during the conduct of the study REGARDLESS of the attribution.

Adverse events are graded on a scale from 1-5: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death. AE grading was per Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table V2.1, Corrected Version 2.1, July 2017)

The primary manuscript outcome measure includes data through week 65 up to September 25, 2023

Safety set: All participants who started assigned study treatment.

Posted

Count of Participants

Participants

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001

Secondary

Proportion of Participants With Favorable Clinical/Bacteriologic Outcome (Definition A) at 65 Weeks Post-randomization

Favorable Outcome are:

liquid culture negative at week 65
without signs or symptoms of ongoing active TB and unable to produce sputum at 65 weeks
who at the end of the follow-up period are clinically without signs/symptoms of ongoing active TB and produce a sputum specimen that is contaminated in two liquid cultures without evidence of TB

Unfavorable:

Absence of cure: Having a sputum sample at or after EOT that is culture-positive (any medium) with a second positive sample obtained 4 hours following the first sample.
Death from any cause except for violent or accidental cause
Had a positive culture for Mtb when last seen
Had a treatment extension beyond nominal level due to clinically inadequate response

Unevaluable are:

lost to follow-up during treatment or post-treatment with their last culture being negative for Mtb
violent or accidental death
becoming pregnant during their assigned active treatment and stop their assigned treatment.

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Number

95% Confidence Interval

proportion of participants

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Secondary

Proportion of Participants With Favorable Composite Outcome (Definition B) at 65 Weeks Post-randomization

Favorable Outcome are:

Same as definition A

Unfavorable:

Same as definition A and:

lost to follow-up during treatment phase
failing to complete treatment
receiving any one or more of the following: extension of treatment beyond the nominal level, except to make up missed doses; re-starting treatment following >= 30 consecutive days lost to follow-up; a change in at least one drug in treatment regimen for any reason except re-infection, pregnancy, or temporary drug challenge

Unevaluable are:

lost to follow-up after treatment phase, and not assessable at the end of follow-up, with their last culture being negative for Mtb
Violent death or accidental death
Women who become pregnant during their assigned active treatment and stop their assigned treatment

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Number

95% Confidence Interval

proportion of participants

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Secondary

Number of Participants Who Prematurely Discontinue Their Treatment Regimen Through 65 Weeks

Premature discontinuation is defined as discontinuation other than due to violent death, natural disaster, or administrative censoring

Safety set: All participants who started assigned study treatment.

Posted

Count of Participants

Participants

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Mean QTcF

QT interval measured as the average of three electrocardiogram (ECG) readings taken 5-10 minutes apart, corrected with Fridericia correction

Limited to available data

Posted

Mean

Standard Deviation

Measured at Weeks 2, 8, and 13 (end of investigational treatment)

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

QTcF Interval Mean Change From Baseline

Mean change from baseline in mean QTcF at weeks 2, 8, and end of treatment (EOT)

Limited to participants with available data

Posted

Mean

Standard Deviation

Measured at baseline and Weeks 2, 8, and 13 (end of investigational treatment)

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Categorized QTcF

Absolute QTcF was categorized as:< 480; ≥480 ms and <500 ms; ≥500 ms

Safety set: participants who started Arm 1 and Arm 2 and with data available.

Posted

Count of Participants

Participants

Week 2, 8, and Week 13

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Categorized Change From Baseline

Categorized change from baseline as: change from baseline of <30 ms; change from baseline of ≥30 ms and <60 ms; change from baseline of ≥60 ms

Limited to the safety analysis set, participants who started assigned treatment, in Arm 1 and Arm 2 and with available data.

Posted

Count of Participants

Participants

Measured at Weeks 2, 8, and Week 13

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Time to Stable Culture Conversion in Liquid Media Through Week 65

Defined as the first of two (consecutive or non-consecutive) negative sputum cultures without an intervening positive culture, and/or visits wherein the participant is unable to produce sputum and has no signs of active TB

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Median

Inter-Quartile Range

weeks

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Time to Stable Culture Conversion in Solid Media Through Week 65

If a participant did not culture convert, they were censored at their last culture result (regardless of result). If a participant died before conversion, the death was considered as a competing event. Participants who were lost to follow-up prior to 65 weeks with their last culture being positive were censored at 65 weeks (i.e. assumed they did not have a culture conversion by week 65), and participants who were lost to follow-up prior to 65 weeks with their last culture being negative were censored at the last sampling visit for which they had a valid culture result.

Adjusted model adjusts for HIV-1 status (positive/negative) and TB Disease at Screening (Advanced/Not Advanced).

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Median

Inter-Quartile Range

weeks

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Secondary

Number of Participants Achieving Stable Liquid Culture Conversion by Week 8

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Count of Participants

Participants

From entry through Week 8

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Number of Participants Achieving Stable Solid Culture Conversion by Week 8

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Count of Participants

Participants

From entry through Week 8

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Number of Participants With One or More Serious Adverse Events (SAEs)

Cumulative proportion with at least one Serious Adverse Event (SAE)

A SAE is defined as any untoward medical occurrence that:

Results in death
Is life-threatening
Requires inpatient hospitalization or prolongation of existing hospitalization
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
Is an important medical event that many not be immediately life-threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the other outcomes listed in the definition above.

Safety set: All participants who started assigned study treatment.

Posted

Count of Participants

Participants

From entry through Week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001

Secondary

Number of Participants Achieving Stable Solid Culture Conversion by Week 12

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions.

Posted

Count of Participants

Participants

From entry through Week 12

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Median Time (Days) to Positivity in Liquid Culture (MGIT)

Time (days) to positivity in liquid culture (MGIT) is defined as the number of days it takes for the culture to produce results up to a max of 42 days. For negative culture results, time to positivity is imputed as 42 days.

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions with data available.

Posted

Median

Inter-Quartile Range

days

From screening, entry, weeks 1, 2, 3, 4, 6, 8, 10, 12

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Change in Chest X-ray Score From Baseline to End of Treatment in Each Arm

The chest X-ray was posterior-anterior. Extent of disease (limited to one lobe or region, unilateral, bilateral, or diffuse) and cavitation status (cavities present [location] or absent) was documented by validated numerical score (percent of total lung affected by any pathology + 40 if cavitation is present; 0 = No percent affected, 140 = entire lung is affected + cavitation is present) for grading chest X-ray in adult smear-positive pulmonary TB (Thorax 2010; 65(10):863-9).

Analysis was conducted based on site readings of CXR

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions and had data available at both time points.

Posted

Mean

95% Confidence Interval

score on a scale

Entry, End of Treatment (Week 13 for Arm 1 and Week 26 for Arm 2)

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Secondary

Proportion of Participants Who Have a TB Relapse, From End of Treatment Until Week 65

The time of relapse is defined as the time from end of treatment until the first sputum sample that is culture positive in liquid or solid media for an Mtb strain that has matching genotype with the baseline isolate (as determined by whole genome sequencing). A second positive sputum sample obtained at least 4 hours following the first sputum collection is required to confirm a relapse. If the second sputum sample was negative, this was not counted as a relapse. If a participant was lost to follow-up without a second sputum sample confirmation of relapse (including contaminated or missing), it was counted as a relapse.

Whole genome sequencing of samples, which is necessary to assess TB relapse, was not performed due to lack of funding. There is no plan to test these samples in the future.

No participants have results as results for whole genome sequencing, which is necessary to assess TB relapse, was not performed due to lack of funding. There is no plan to test these samples in the future.

Posted

From end of treatment (week 13 for Arm 1; week 26 for Arm 2) to week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Secondary

Cumulative Proportion of Participants Who Have a TB Recurrence, From End of Treatment Until Week 65

The time of recurrence is defined as the time from end of treatment until the first sputum sample that is culture positive in liquid or solid media. A second positive sputum sample obtained at least 4 hours following the first sputum collection is required to confirm a recurrence. If the second sputum sample was negative, this will not be counted as a recurrence. If a participant was lost to follow-up without a second sputum sample confirmation of recurrence (including contaminated or missing), it was counted as a recurrence.

Participants at risk for recurrence where those who were stable culture conversions by end of treatment.

Efficacy set: All participants who were randomized to study treatment Arm 1 or Arm 2 and were not late exclusions and at risk for TB Recurrence

Posted

Number

95% Confidence Interval

proportion of participants

From end of treatment (week 13 for Arm 1; week 26 for Arm 2) to week 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily

Secondary

Pharmacokinetic Parameter for CFZ: Minimum Concentration (Cmin)

Estimated using noncompartmental methods applied to concentrations from intensive PK sampling visits at weeks 2 and 13.

Intensive PK tests were performed at weeks 2 and 13 on Arm 1 participants who consent and were registered to the Intensive PK subgroup and at week 2 on Arm C participants.

Posted

Mean

Standard Deviation

mg/L

Measured at Weeks 2 and 13

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm C: PK Only Subgroup	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks). Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine: (CFZ) 100 mg once daily

Secondary

Pharmacokinetic Parameter for CFZ: Maximum Concentration (Cmax)

Estimated using noncompartmental methods applied to concentrations from intensive PK sampling visits at weeks 2 and 13.

Intensive PK tests were performed at weeks 2 and 13 on Arm 1 participants who consent and were registered to the Intensive PK subgroup and at week 2 on Arm C participants.

Posted

Mean

Standard Deviation

mg/L

Measured at Weeks 2 and 13

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm C: PK Only Subgroup	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks). Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine: (CFZ) 100 mg once daily

Secondary

Pharmacokinetic Parameter for CFZ: Time of Cmax (Tmax)

Estimated using noncompartmental methods applied to concentrations from intensive PK sampling visits at weeks 2 and 13.

Intensive PK tests were performed at weeks 2 and 13 on Arm 1 participants who consent and were registered to the Intensive PK subgroup and at week 2 on Arm C participants.

Posted

Mean

Standard Deviation

hours

Measured at Weeks 2 and 13

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm C: PK Only Subgroup	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks). Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine: (CFZ) 100 mg once daily

Secondary

Pharmacokinetic Parameter for CFZ: Area Under the Concentration Curve (AUC0-24h)

Estimated using noncompartmental methods applied to concentrations from intensive PK sampling visits at weeks 2 and 13.

Intensive PK tests were performed at weeks 2 and 13 on Arm 1 participants who consent and were registered to the Intensive PK subgroup and at week 2 on Arm C participants.

Posted

Mean

Standard Deviation

mg/L*h

Measured at Weeks 2 and 13

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm C: PK Only Subgroup	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks). Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine: (CFZ) 100 mg once daily

Secondary

Mean Change From Baseline in Skin Pigmentation (Colorimetric L*)

The median of triplicate measurements of Inner Arm, and Face (median of all measurements from the Chin, Forehead, Left Cheek, and Right Cheek). L represents lightness (0 = black, 100 = white).

Further data processing removed values if one of the triplicates differed more than 5% of the median.

Limited to the safety analysis set, participants who started assigned treatment, and were not premature study discontinuations before week 8 and had data available.

Posted

Mean

Standard Deviation

units on a scale

Entry, Weeks 8, 13, 26, and 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Mean Change From Baseline in Skin Pigmentation (Colorimetric a*)

The median of triplicate measurements of Inner Arm, and Face (median of all measurements from the Chin, Forehead, Left Cheek, and Right Cheek). The a* parameter represents the balance between red and green. Positive values of a* indicate a reddish tone, while negative values indicate a greenish tone. (-128 = Green, 127 = Red).

Further data processing removed values if one of the triplicates differed more than 5% of the median.

Limited to the safety analysis set, participants who started assigned treatment, and were not premature study discontinuations before week 8 and had data available.

Posted

Mean

Standard Deviation

units on a scale

Entry, Weeks 8, 13, 26, and 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care

Secondary

Mean Change From Baseline in Skin Pigmentation (Colorimetric b*)

The median of triplicate measurements of Inner Arm, and Face (median of all measurements from the Chin, Forehead, Left Cheek, and Right Cheek). The b* parameter represents the balance between yellow and blue. Positive values of b* indicate a yellowish tone, while negative values indicate a bluish tone (-128 = Blue, 127 = Yellow).

Further data processing removed values if one of the triplicates differed more than 5% of the median.

Limited to the safety analysis set, participants who started assigned treatment, and were not premature study discontinuations before week 8 and had data available.

Posted

Mean

Standard Deviation

units on a scale

Entry, Weeks 8, 13, 26, and 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care

Secondary

Change From Baseline in Participant-reported Changes in Skin Pigment Related to Perceived Skin Hyperpigmentation

Subjective questionnaire asked the following questions :

1.) On a scale from 0 to 10: (0 being none and 10 being most significant possible) How would you rate any change in the coloration of your skin since you began TB treatment?

Participants in Arm 1 and Arm 2 with follow-up after week 8

Posted

Mean

Standard Deviation

score on a scale

Entry, Weeks 8, 13, 26, and 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Secondary

Change From Baseline in Participant-reported Distress Caused by Change in Skin Pigment Related to Perceived Skin Hyperpigmentation

Subjective questionnaire asked the following questions:

On a scale from 0 to 10: (0 being none and 10 being worst possible) How would you rate your distress to skin coloration changes since you began TB treatment, if any?

Participants in Arm 1 and Arm 2 with follow-up after week 8

Posted

Mean

Standard Deviation

score on a scale

Entry, Weeks 8, 13, 26, and 65

ID	Title	Description
OG000	Arm 1: Experimental	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Rifapentine: (P) 1200 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg Clofazimine loading dose: (CFZ) 300 mg once daily for 2 weeks (loading dose), then 100 mg once daily
OG001	Arm 2: Standard of Care	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Rifampicin: (R) 600 mg once daily Isoniazid: (H) 300 mg once daily Pyrazinamide: (Z) 1000mg once daily if weight is 40 to <55kg; 1500mg once daily if weight is 55to <71kg; 2000mg once if weight is ≥71kg Ethambutol: (E) 800 mg once daily if weight is 40 to <55kg; 1200 mg once daily if weight is 55 to <71kg; 1600mg once if weight is ≥71kg

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1	Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Doses (administered orally once daily): rifapentine, 1200mg; isoniazid, 300mg; pyrazinamide, 40 to <55kg 1000mg, 55to <71kg 1500mg; ≥71kg 2000mg; ethambutol, 40 to <55kg 800mg, 55to <71kg 1200mg; ≥71 kg 1600mg Rifapentine: 1200 mg once daily Isoniazid: 300 mg once daily Pyrazinamide: 1000mg once daily if weight is 40 to <55kg 1500mg once daily if weight is 55to <71kg 2000mg once if weight is ≥71kg Ethambutol: 800 mg once daily if weight is 40 to <55kg 1200 mg once daily if weight is 55 to <71kg 1600mg once if weight is ≥71kg Clofazimine: 300 mg once daily for 2 weeks (loading dose). 100 mg once daily	1	58	8	58	25	58
EG001	Arm 2	Participants received rifampicin/isoniazid/pyrazinamide/ethambutol (RHZE) for 8 weeks; then rifampicin/isoniazid (RH) for 18 weeks. Doses (administered orally once daily): rifampicin, 600mg; isoniazid, 300mg; pyrazinamide, 40 to <55kg 1000mg, 55to <71kg 1500mg; ≥71 kg 2000mg; ethambutol, 40 to <55kg 800mg, 55to <71kg 1200mg; ≥71 kg 1600mg Rifampicin: 600 mg once daily Isoniazid: 300 mg once daily Pyrazinamide: 1000mg once daily if weight is 40 to <55kg 1500mg once daily if weight is 55to <71kg 2000mg once if weight is ≥71kg Ethambutol: 800 mg once daily if weight is 40 to <55kg 1200 mg once daily if weight is 55 to <71kg 1600mg once if weight is ≥71kg	1	31	2	31	7	31
EG002	Arm C	Participants received PHZE + CFZ 100 mg once daily for 4 weeks; then remained on study, and were treated with off study medications according to local SOC (RHZE for 4 weeks; then RH for 18 weeks). Doses (for on study medications; administered orally once daily): rifapentine, 1200mg; isoniazid, 300mg; pyrazinamide, 40 to <55kg 1000mg, 55to <71kg 1500mg; ≥71 kg 2000mg; ethambutol, 40 to <55kg 800mg, 55to <71kg 1200mg; ≥71 kg 1600mg Rifapentine: 1200 mg once daily Isoniazid: 300 mg once daily Pyrazinamide: 1000mg once daily if weight is 40 to <55kg 1500mg once daily if weight is 55to <71kg 2000mg once if weight is ≥71kg Ethambutol: 800 mg once daily if weight is 40 to <55kg 1200 mg once daily if weight is 55 to <71kg 1600mg once if weight is ≥71kg Clofazimine: 300 mg once daily for 2 weeks (loading dose). 100 mg once daily	1	15	2	15	3	15
EG003	Arm 1 (Extension of Follow-up)	DSMB Recommended Extension of follow-up for participants in Arm 1 who were still in follow-up through Week 65. Participants received rifapentine/isoniazid/pyrazinamide/ethambutol (PHZE) + clofazimine (CFZ) 300 mg once daily for 2 weeks; then PHZE + CFZ 100 mg once daily for 6 weeks; then rifapentine/isoniazid/pyrazinamide (PHZ) + CFZ 100 mg once daily for 5 weeks. Doses (administered orally once daily): rifapentine, 1200mg; isoniazid, 300mg; pyrazinamide, 40 to <55kg 1000mg, 55to <71kg 1500mg; ≥71kg 2000mg; ethambutol, 40 to <55kg 800mg, 55to <71kg 1200mg; ≥71 kg 1600mg Rifapentine: 1200 mg once daily Isoniazid: 300 mg once daily Pyrazinamide: 1000mg once daily if weight is 40 to <55kg 1500mg once daily if weight is 55to <71kg 2000mg once if weight is ≥71kg Ethambutol: 800 mg once daily if weight is 40 to <55kg 1200 mg once daily if weight is 55 to <71kg 1600mg once if weight is ≥71kg Clofazimine: 300 mg once daily for 2 weeks (loading dose). 100 mg once daily	0	29	2	29	1	29

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cor pulmonale	Cardiac disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG0030 affected29 at risk
Incarcerated inguinal hernia	Gastrointestinal disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Ocular icterus	Hepatobiliary disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Cerebral toxoplasmosis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Disseminated tuberculosis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Immune reconstitution inflammatory syndrome associated tuberculosis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Pneumonia	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Pulmonary tuberculosis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Gun shot wound	Injury, poisoning and procedural complications	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0002 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 28.0	Systematic Assessment	EG0002 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG0030 affected29 at risk
Chest pain	General disorders	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Pneumonia	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Pulmonary tuberculosis	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Scabies	Infections and infestations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0004 affected58 at risk EG0011 affected31 at risk EG0021 affected15 at risk EG003
Bilirubin conjugated increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Blood albumin decreased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Blood creatinine increased	Investigations	MedDRA 28.0	Systematic Assessment	EG00014 affected58 at risk EG0013 affected31 at risk EG0020 affected15 at risk EG003
Blood glucose increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Lipase increased	Investigations	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Weight decreased	Investigations	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Abnormal loss of weight	Metabolism and nutrition disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Glycosuria	Renal and urinary disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0011 affected31 at risk EG0020 affected15 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	MedDRA 28.0	Systematic Assessment	EG0001 affected58 at risk EG0010 affected31 at risk EG0020 affected15 at risk EG003
Hypertension	Vascular disorders	MedDRA 28.0	Systematic Assessment	EG0000 affected58 at risk EG0010 affected31 at risk EG0021 affected15 at risk EG003

Enrollment to this study was terminated early based on a recommendation from the independent DSMB for the study. This was due to the high rate of unfavorable outcomes and recurrences in Arm 1. As a consequence, the study had reduced precision to evaluate the primary biomarker outcome related to time to stable culture conversion.

Certain Agreements

Point of Contact

Title	Organization	Phone	Extension	Email
ACTG Clinicaltrials.gov Coordinator	ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company	(301) 628-3348		ACTGCT.gov@fstrf.org

First MCP Posted Date

ID	Term
D014376	Tuberculosis

Ancestor Terms

ID	Term
D009164	Mycobacterium Infections
D000193	Actinomycetales Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
C018421	rifapentine
D012293	Rifampin
D007538	Isoniazid
D011718	Pyrazinamide
D004977	Ethambutol
D002991	Clofazimine

Ancestor Terms

ID	Term
D012294	Rifamycins
D006576	Heterocyclic Compounds, 4 or More Rings
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D047029	Lactams, Macrocyclic
D047028	Macrocyclic Compounds
D011083	Polycyclic Compounds
D006834	Hydrazines
D009930	Organic Chemicals
D007539	Isonicotinic Acids
D000147	Acids, Heterocyclic
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D011719	Pyrazines
D005029	Ethylenediamines
D003959	Diamines
D011073	Polyamines
D000588	Amines
D010619	Phenazines
D006575	Heterocyclic Compounds, 3-Ring