| CTRI Number |
CTRI/2025/07/091671 [Registered on: 24/07/2025] Trial Registered Prospectively |
| Last Modified On: |
22/07/2025 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Drug |
| Study Design |
Randomized, Parallel Group Trial |
|
Public Title of Study
|
A5409 - A Phase 2 Randomized, Adaptive, Dose- Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (RAD-TB). |
|
Scientific Title of Study
|
A Phase 2 Randomized, Adaptive Dose- Ranging, Open-Label Trial of Novel Regimens for the Treatment of Pulmonary Tuberculosis (RAD-TB). |
| Trial Acronym |
Nill |
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NCT06192160 |
ClinicalTrials.gov |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Sanjay Gaikwad |
| Designation |
Professor and Head |
| Affiliation |
BJ Medical College and Sassoon General Hospital |
| Address |
Department of pulmonary Medicine BJ Medical College and Sassoon General Hospital Jai Prakash Narayan Road Pune
Pune
MAHARASHTRA
411001
India |
| Phone |
02026052419 |
| Fax |
|
| Email |
drsanjaytbres@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Vidya Mave |
| Designation |
CRS Leader |
| Affiliation |
BJ Medical College Clinical Trail Unit |
| Address |
B J Medical Government College and Sassoon General Hospitals 1st Floor Animal House Behind BJGMC Building
Jai Prakash Narayan Road Pune
Pune
MAHARASHTRA
411001
India |
| Phone |
9503646148 |
| Fax |
|
| Email |
vidyamave@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Nishi Suryavanshi |
| Designation |
CRS Coordinator |
| Affiliation |
BJ Medical College Clinical Trail Unit |
| Address |
B J Medical Government College and Sassoon General Hospitals 1st Floor Animal House Behind BJGMC Building
Jai Prakash Narayan Road Pune
Pune
MAHARASHTRA
411001
India |
| Phone |
9823248979 |
| Fax |
|
| Email |
nishisuryavanshi@hotmail.com |
|
|
Source of Monetary or Material Support
|
| National Institutes of Health. 6700 Rockledge Drive, Bethesda, Maryland 20817, USA
|
|
|
Primary Sponsor
|
| Name |
NIH DAIDS |
| Address |
6700 Rockledge Drive Bethesda Maryland 20817 USA
|
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
| Name |
Address |
| B J Govt Medical College Sassoon General Hospitals B J Medical College Clinical trial Unit |
Jai Prakash Narayan Road, Maharashtra (India) 411001 |
|
|
Countries of Recruitment
|
Botswana
Brazil
Haiti
India
Kenya
Malawi
Mexico
Peru
Philippines
South Africa
Thailand
Uganda
Zimbabwe |
|
Sites of Study
|
| No of Sites = 1 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Sandesh patil |
B. J. Medical College - JHU Clinical Trail Unit |
B J Medical College and Sassoon General Hospitals 1st Floor Animal House Behind BJGMC Building
Jai Prakash Narayan Road Pune
Pune
MAHARASHTRA |
9158050099
camsandesh14@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Ethics Committee-B J medical college & Sassoon General Hospitals |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: A150||Tuberculosis of lung, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
Bedaquiline |
BDQ 400 mg will be administered as four 100 mg tablets orally once daily with a meal for the first 2 weeks followed by 200 mg (two 100 mg tablets) orally once daily with a meal for 6 weeks. |
| Comparator Agent |
Ethambutol |
EMB will be administered as 400 mg tablets, based on weight (Table 5.1.1-2), orally once daily. |
| Comparator Agent |
Isoniazid |
INH 300 mg will be administered as one tablet orally once daily. All participants in the SOC arm must receive pyridoxine (vitamin B6) with each study-provided dose of INH based on current local, national, or international dosing guidelines. |
| Intervention |
Linezolid |
LZD 600 mg will be administered as one 600 mg tablet orally once daily. To avoid a sudden and dangerous increase in blood pressure, large quantities of foods or beverages with high tyramine content should be avoided while taking linezolid. See the A5409 Manual of Procedures (MOPS) for a full list of foods with high tyramine content. |
| Intervention |
Pretomanid |
Pa 200 mg will be administered as one 200 mg tablet orally once daily with a meal. |
| Comparator Agent |
Pyrazinamide |
PZA will be administered as 500 mg tablets, based on weight (Table 5.1.1-2), orally once daily. |
| Comparator Agent |
Rifampicin |
RIF 600 mg will be administered as two 300 mg capsules orally once daily on an empty stomach, 1 hour before or 2 hours after eating a meal. |
| Intervention |
Sutezolid |
SZD 800 mg once daily and 1600 mg once daily will be administered as two or four 400 mg tablets orally once daily with a meal. |
| Intervention |
TBI-223 |
TBI-223 1200 mg once daily and 2400 mg once daily will be administered as two or four 600 mg tablets orally once daily with a meal. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
75.00 Year(s) |
| Gender |
Both |
| Details |
pulmonary TB among individuals either without history of prior TB treatment or with history of TB treatment more than 5 years prior to study entry identified within 7 days prior to study entry by at least one sputum specimen positive for Mtb by Xpert Semiquantitative Mtb results of medium or high are required
Pulmonary TB with documented INH susceptibility by Line Probe Assay LPA or Xpert MTB XDR or other validated molecular test and with documented RIF susceptibility by LPA or Xpert MTBRIF or Xpert MTBRIF Ultra or other validated molecular test within 7 days prior to study entry
Documentation of HIV1 infection status as below
Presence or Absence of HIV1 infection as documented by
Any licensed rapid HIV test or HIV1 enzyme or chemiluminescence immunoassay ECIA test kit any time prior to study entry AND
Confirmed by one of the following
A second antibody test from different manufacturers or based on different principles and epitopes combination antigenantibodybased rapid tests may be used or
HIV1 antigen or
Plasma HIV1 RNA viral load or
A licensed Western blot
For individuals with HIV CD4 cell count 100 cellsmm3 based on testing performed within 30 days prior to study entry
For individuals with HIV Currently being treated with dolutegravir-based antiretroviral therapy ART or plan to initiate dolutegravir-based ART at or before study week 8
Individuals age 18 years
The following laboratory values obtained within 7 days prior to study entry at any network-approved nonUS laboratory that operates in accordance with Good Clinical Laboratory Practices GCLP and participates in appropriate external quality assurance programs
Serum or plasma alanine aminotransferase ALT3 times the upper limit of normal ULN
Serum or plasma total bilirubin 2 times ULN
Serum or plasma creatinine 2 times ULN
Serum or plasma potassium 3 5 mEqL
Serum or plasma magnesium 1 0 mEqL 0 500 mmolL
Absolute neutrophil count ANC 1500mm3
Hemoglobin 9 5 gdL for individuals assigned to female sex at birth and 10 g dL for individuals assigned to male sex at birth
Platelet count 100000 mm3
Negative for hepatitis B core antibody HBcAb total hepatitis B surface antigen HBsAg
Negative for hepatitis C virus HCV antibody or if HCV antibody positive must have a negative HCV PCR
For individuals assigned to female sex at birth and who are of reproductive potential negative pregnancy test urine HCG or serum βHCG within 3 days 72 hours prior to entry by any network approved nonUS laboratory or clinic that operates in accordance with GCLP and participates in appropriate external quality assurance programs
Individuals assigned to female sex at birth who are of reproductive potential and who participate in sexual activity that could lead to pregnancy must agree to use at least two of the following forms of birth control while receiving TB study medications and for 12 months after stopping study medications
Male or female condoms
Diaphragm or cervical cap with spermicide if available
Intrauterine device IUD or intrauterine system IUS
Hormone based birth control eg oral contraceptives DepoProvera NuvaRing implants
For individuals who are assigned male sex at birth who engage in sexual activity that may lead to pregnancy in their partner must agree to either remain abstinent or use male contraceptives They are also strongly advised to inform their nonpregnant sexual partners of reproductive potential to use effective contraceptives while the individual is on study and for 90 days after experimental treatment discontinuation
For individuals assigned male sex at birth with pregnant partners willingness to use condoms during vaginal intercourse while on study and for 90 days after experimental treatment discontinuation
For individuals assigned male sex at birth willingness to refrain from sperm donation while on study and for 90 days after experimental treatment discontinuation
Documentation of Karnofsky performance score 60 obtained within 14 days prior to study entry
Chest xray obtained within 14 days prior to study entry
A verifiable address or residence readily accessible for visiting and willingness to inform the study team of any change of address during study treatment and follow-up period
Ability and willingness of individual to provide informed consent
|
|
| ExclusionCriteria |
| Details |
More than cumulative 7 days of treatment directed against active TB for the current TB episode in the 60 days preceding study entry
Current extrapulmonary TB in the opinion of the investigator
QTcF interval 450 ms within 7 days prior to study entry
History of or ongoing heart failure
Personal or family history of congenital QT prolongation
History of known untreated ongoing hypothyroidism
History of or ongoing bradyarrhythmia
History of torsades de pointes
Current Grade 2 or higher peripheral neuropathy
Other medical conditions eg diabetes liver or kidney disease blood disorders chronic diarrhea in the opinion of the site investigator in which the current clinical condition of the participant is likely to prejudice the response to or assessment of treatment
Pregnant or breastfeeding or planning to become pregnant within the next 12 months
Weight 35 kg
Unable to take oral medications
Taking any of prohibited medications
Known allergy sensitivity or any hypersensitivity to components of investigational agents or their formulation
Active drug or alcohol use or dependence or mental illness eg major depression that, in the opinion of the site investigator would interfere with adherence to study requirements
Taking an investigational drug or vaccine within 30 or more days prior to study entry |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Not Applicable |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
Difference in mean log10 (Time to positivity (TTP)) slope from longitudinal mycobacteria growth indicator tube (MGIT) liquid culture measurements over the first 6 weeks of treatment [ Time Frame: Weeks 0, 1, 2, 3, 4 and 6 ]
for each experimental treatment arm compared to the SOC arm
Difference in the cumulative proportion of participants having at least one new Grade 3 or higher adverse event (AE) by week 8 of treatment [ Time Frame: 8 weeks ]
for each experimental treatment arm compared to the SOC arm |
8 weeks |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
Cumulative proportion of participants with stable sputum culture conversion by week 8 as measured by culture-negative status via MGIT liquid culture at two consecutive measurements
Mean log10 TTP slope from longitudinal MGIT liquid culture measurements over the first 8 weeks of treatment
Cumulative proportion of participants with a new Grade 3 or higher AE by week 26 of treatment
Cumulative proportion of participants with permanent discontinuation of study provided antiTB drugs due to any reason prior to Week 8 of treatment
Cumulative proportion of participants with permanent discontinuation or temporary discontinuation for 3 days of at least one antiTB drug due to any reason prior to week 8 of treatment
Cumulative proportion of participants with permanent discontinuation of at least one antiTB drug due to any reason prior to week 26 of treatment
A composite of stable culture conversion at week 6 of treatment and no new Grade 3 or higher AE through week 8 |
52 weeks |
|
|
Target Sample Size
|
Total Sample Size="315"
Sample Size from India="70"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 2 |
|
Date of First Enrollment (India)
|
03/11/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
15/06/2025 |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="1"
Months="0"
Days="13" |
|
Recruitment Status of Trial (Global)
|
Open to Recruitment |
| Recruitment Status of Trial (India) |
Not Yet Recruiting |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
A5409/RAD-TB is an adaptive Phase 2 randomized, controlled, open-label, dose-ranging, platform protocol to evaluate the safety and efficacy of multidrug regimens for the treatment of adults with drug-susceptible pulmonary tuberculosis (TB). A5409 hypothesizes that novel regimens for the treatment of pulmonary tuberculosis will result in superior early efficacy, as determined by longitudinal mycobacteria growth indicator tube (MGIT) liquid culture time to positivity (TTP) measurements over the first 6 weeks of treatment, and will have acceptable safety and tolerability over 8 weeks of treatment relative to standard of care [(SOC) isoniazid/rifampicin/pyrazinamide/ethambutol (HRZE)]. The study will run for 52 weeks, inclusive of 26 weeks of TB treatment comprised of 8 weeks of experimental or SOC treatment (based on treatment arm assignment) followed by 18 weeks of SOC treatment with 45 participants in each experimental treatment arm and at least 90 participants in the SOC arm. |