A Phase IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in Drug-Susceptible Tuberculosis: The CLO-FAST Study
Phase: PHASE2
Conditions: HIV, Tuberculosis
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

 
ACTG NETWORK COORDINATING CENTER 
Social & Scientific Systems, Inc., a DLH Holdings Company 
8757 Georgia Avenue, 12th Floor 
Silver Spring, MD  20910-3714 
Phone: 301-628-3000 
 
 
 
CLARIFICATION MEMO 
 
DATE:  
December 12, 2022 
 
TO: 
 
ACTG CTU Principal Investigators, CRS Leaders, and CTU/CRS Coordinators 
 
FROM: 
A5362 Protocol Team  
 
SUBJECT: 
Clarification Memo #1 for Protocol A5362, Version 2.0 
 
 
This clarification memo (CM) does not result in a change in the protocol informed 
consent document. The Division of AIDS does not require you to forward it to your 
institutional review board (IRB); however, you must follow your IRB’s policies and 
procedures. If IRB review of clarification memos is required at your site, please submit 
this document for review. 
 
Each site should file a copy of this CM with the protocol for reference. 
 
Clarifications are being made to Protocol A5362, Version 2.0, 08Jul2022, titled, “A Phase 
IIc Trial of Clofazimine- and Rifapentine-Containing Treatment Shortening Regimens in 
Drug-Susceptible Tuberculosis: The CLO-FAST Study.” The clarifications are described 
below and should be implemented immediately. These clarifications will be included in 
the next version of the A5362 protocol if it is amended at a future date. 
 
This CM is being issued to: 
• 
Clarify inclusion criterion 4.1.1, for the identification of pulmonary TB within 5 days prior to 
entry by sputum sample. 
• 
Move section 5.3 (Pharmacy: Product Supply, Distribution, and Accountability) to the correct 
location in the protocol.  
• 
Clarify site enrollment capacity for the qualitative interview subgroup in section 6.3.17. 
• 
Remove duplicate secondary outcome 10.2.2.1.B. 
 
1. Inclusion criterion 4.1.1 reads: 
 
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. 
 

 
The team would like to clarify that the sputum sample does not have to be collected within 5 
days of the initial diagnosis, but can be any positive sputum sample collected within 5 days 
prior to study entry.  
 
2. Section 5.3 (Pharmacy: Product Supply, Distribution, and Accountability) was inadvertently 
placed in section 6.0 (Clinical and Laboratory Evaluations); therefore, section 5.3 is being 
moved to its correct location (noted in bold or strikethrough) between section 5.2 
(Formulations and Preparation) and section 5.4 (Concomitant Medications).  
 
• 
Section 5.3 (Pharmacy: Product Supply, Distribution, and Accountability) 
 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability  
 
5.3.1  Study Product Acquisition/Distribution  
 
Clofazimine (Lamprene®) will be manufactured by Novartis.  
 
Rifapentine (Priftin®) will be manufactured by Sanofi.  
 
Isoniazid, pyrazinamide, ethambutol, and rifampicin will be 
manufactured by Macleods Pharmaceuticals. 
 
Study products will be purchased through ACTG Leadership and 
Operations and made available through the NIAID Clinical Research 
Products Management Center (CRPMC). The site pharmacist should 
obtain the study product(s) for this protocol by following the 
instructions in the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks. 
 
Antiretroviral medications are NOT provided through the study and 
must be obtained locally by the site. Selection and dosing of ART in 
combination with RIF or RPT should adhere to local guidelines at 
each site.  
 
Pyridoxine (vitamin B6) will NOT be provided through the study and 
must be obtained locally by the site. 
 
5.3.2 Study Product Accountability 
 
The site pharmacist is required to maintain complete records of all 
study products received from the NIAID CRPMC and subsequently 
dispensed. The site pharmacist at non-US CRSs must follow the 
instructions in the Pharmacy Guidelines and Instructions for DAIDS 
Clinical Trials Networks for the destruction of unused study 
products. 
 
• 
Section 6.0 (Clinical and Laboratory Evaluations) 
 
6.0 
CLINICAL AND LABORATORY EVALUATIONS 
 
5.3 
Pharmacy: Product Supply, Distribution, and Accountability  
 

 
5.3.1  Study Product Acquisition/Distribution  
 
Clofazimine (Lamprene®) will be manufactured by Novartis.  
 
Rifapentine (Priftin®) will be manufactured by Sanofi.  
 
Isonazid, pyrazinamide, ethambutol and rifampicin will be manufactured 
by Macleods Pharmaceuticals. 
 
Study products will be purchased through the ACTG Leadership and 
Operations and made available through the NIAID Clinical Research 
Products Management Center (CRPMC). The site pharmacist should 
obtain the study product(s) for this protocol by following the instructions in 
the Pharmacy Guidelines and Instructions for DAIDS Clinical Trials 
Networks. 
 
Antiretroviral medications are NOT provided through the study and must 
be obtained locally by the site. Selection and dosing of ART in 
combination with RIF or RPT should adhere to local guidelines at each 
site.  
 
Pyridoxine (vitamin B6) will NOT be provided through the study and must 
be obtained locally by the site. 
 
5.3.2 Study Product Accountability 
 
The site pharmacist is required to maintain complete records of all study 
products received from the NIAID CRPMC and subsequently dispensed. 
The site pharmacist at non-US CRSs must follow the instructions in the 
Pharmacy Guidelines and Instructions for DAIDS Clinical Trials Networks 
for the destruction of unused study products. 
 
3. The team added the site enrollment capacity for the qualitative interview subgroup to section 
6.3.17 (Open-Ended Qualitative Interview: Arm 1 and Arm 2 Only). To note, once sites reach 
enrollment capacity of six participants (three per Arm 1 and three per Arm 2), sites are 
responsible for updating their site-specific informed consent, following their local standard 
operating procedures and institutional review board guidelines. 
 
6.3.17 Open-Ended Qualitative Interview: Arm 1 and Arm 2 Only 
 
An open-ended interview will be conducted in 20 consenting participants in each arm 
balanced by site to obtain ethnographic data on the impact of perceived skin color 
changes on their quality of life. Each site has an enrollment capacity of six 
participants (three per Arm 1 and three per Arm 2) to the qualitative interview 
subgroup. The protocol data managers will inform sites when they reach their 
enrollment capacity.  
 
4. The definitions for secondary outcomes 10.2.2.1.B and 10.2.2.1.C are the same; therefore, 
secondary outcome 10.2.2.1.B is being removed and secondary outcome 10.2.2.1.C will 
remain since 10.2.2.1.C includes reference to the corresponding objective. 
 
10.2.2 Secondary Outcomes 

 
 
10.2.2.1   A. 
Efficacy: proportion with favorable clinical/bacteriologic outcome     
(definition 10.2.4.A) at 65 weeks post-randomization. [Objective 
1.3.8] 
 
B.  Efficacy: proportion with favorable composite outcome including 
treatment completion (definition 10.2.4.B) at 65 weeks post-
randomization.  
 
 
B. Efficacy: proportion with favorable composite outcome including 
treatment completion (definition 10.2.4.B) at 65 weeks post-
randomization. [Objective 1.3.1]