Phase I/II Dose-Finding, Safety, Tolerance, and Pharmacokinetics Study of a Raltegravir-Containing Antiretroviral Therapy (ART) Regimen in HIV-Infected and TB Co-Infected Infants and Children
Phase: PHASE1
Conditions: HIV Infections, Tuberculosis
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Letter of Amendment #2 for: 
 
IMPAACT P1101 
 
Phase I/II Dose-finding, Safety, Tolerance and Pharmacokinetics Study of a Raltegravir-
Containing Antiretroviral Therapy (ART) Regimen in HIV-infected and TB Co-infected 
Infants and Children 
 
A Multicenter, International Trial of the 
International Maternal Pediatric Adolescent AIDS 
Clinical Trials Network (IMPAACT) 
 
Protocol: Version 3.0, dated 24 April 2017 
 
Letter of Amendment Date: 21 June 2018 
 
 
 
NCT 01751568 
 

Letter of Amendment #2       
Page 1 of 3 
21 June 2018 
IMPAACT P1101 Protocol Version 3.0 
Letter of Amendment #2 for: 
IMPAACT P1101 
Phase I/II Dose-finding, Safety, Tolerance and Pharmacokinetics Study of a Raltegravir-
Containing Antiretroviral Therapy (ART) Regimen in HIV-infected and TB Co-infected 
Infants and Children 
Version 3.0, dated 24 April 2017 
 DAIDS Document ID #11831 
IND #77,787 Held By DAIDS 
Letter of Amendment Date: 21 June 2018 
Information/Instructions to Study Sites from the Division of AIDS 
The information contained in this Letter of Amendment (LoA) impacts the IMPAACT P1101 study, and 
must be submitted to site Institutional Review Boards and/or Ethics Committees (IRBs/ECs) as soon as 
possible for their review and approval. Approval must also be obtained from site regulatory entities if 
applicable per the policies and procedures of the regulatory entities. All IRB/EC and regulatory entity 
requirements must be followed. 
Upon receiving IRB/EC approval and any other applicable regulatory entity approvals, all sites should 
immediately begin implementing this LoA. Sites are required to submit a LoA registration packet to the 
DAIDS Protocol Registration Office (DAIDS PRO) at the Regulatory Support Center (RSC). Sites will 
receive a registration notification for the LoA after the DAIDS PRO verifies that all required registration 
documents have been received and are complete. Sites should not await this notification before 
implementing this LoA.  
Please file this LoA, all associated IRB/EC and regulatory entity correspondence, and all correspondence 
with the DAIDS PRO in your essential documents files for P1101. If the P1101 protocol is amended in 
the future, the contents of this LoA will be incorporated into the next version of the protocol. 

Letter of Amendment #2       
Page 2 of 3 
21 June 2018 
IMPAACT P1101 Protocol Version 3.0 
IMPAACT P1101 
Phase I/II Dose-finding, Safety, Tolerance and Pharmacokinetics Study of a Raltegravir-Containing 
Antiretroviral Therapy (ART) Regimen in HIV-infected and TB Co-infected Infants and Children 
 
Version 3.0, dated 24 April 2017 
DAIDS Document ID #11831 
 
Version 3.0, Letter of Amendment #2 
Dated 21 June 2018 
 
Letter of Amendment Signature Page 
 
I will conduct this study in accordance with the provisions of this protocol and all applicable protocol-
related documents. I agree to conduct this study in compliance with United States (US) Health and 
Human Service regulations (45 CFR 46); applicable US Food and Drug Administration regulations; 
standards of the International Conference on Harmonization Guideline for Good Clinical Practice (E6); 
Institutional Review Board/Ethics Committee determinations; all applicable in-country, state, and local 
laws and regulations; and other applicable requirements (e.g., US National Institutes of Health, Division 
of AIDS) and institutional policies. 
 
 
 
 
 
 
 
Signature of Investigator of Record 
 
Date 
 
 
 
 
 
Name of Investigator of Record 
 
 
(printed) 
 

Letter of Amendment #2       
Page 3 of 3 
21 June 2018 
IMPAACT P1101 Protocol Version 3.0 
Summary of Modifications and Rationale 
 
The following modifications are included in this LoA: 
 
1. Sections 6.5, 6.7, and 9.2 are modified to clarify the pharmacokinetic (PK) criteria for early study 
drug discontinuation for participants with AUC0-12hr ≥ 63 µMxhr.  
2. Section 7.2 is updated to clarify that confirmed Grade 3 and 4 adverse events are required to be 
reported as expedited adverse events. 
 
Implementation 
 
Detailed modifications of the protocol text included in this LoA are listed below.  Additions to the text are 
indicated in bold; deletions are indicated by strikethrough.  
 
1. Pharmacokinetic criteria for early study drug discontinuation 
 
a. Section 6.5, Pharmacokinetic Endpoint, second paragraph: 
 
RAL will be stopped in any individual that has an AUC0-12hr ≥ 63 µMxhr, per Section 9.0. Per 
Section 9.0, if any individual has an AUC0-12hr ≥ 63 µMxhr, the Protocol Team will review all 
available clinical, safety, PK, immunologic, and virologic data for the participant and 
determine if discontinuation of RAL is indicated.  For participants that permanently 
discontinue RAL, evaluable PK and safety data will be used in the assessment of the dose 
for that cohort. 
 
b. Section 6.7, Criteria for Early Treatment Discontinuation, fifth bullet: 
 
• Participant has an AUC0-12hr ≥ 63 µMxhr, and the protocol team determines that RAL 
should be permanently discontinued, per Section 9.0. 
 
c. Section 9.2, Study Design, Modeling and Data Analysis, Pharmacokinetic Guidelines, sixth 
paragraph: 
 
If any individual has an AUC0-12hr ≥ 63 µMxhr **, the Protocol Team will review all available 
clinical, safety, PK, immunologic, and virologic data for the participant and determine if 
discontinuation of RAL is indicated participant will stop taking RAL.  However, their For 
participants that permanently discontinue RAL, evaluable PK and safety data will be used in 
the assessment of the dose for that cohort. 
 
2. Expedited Adverse Event Reporting Requirements 
 
Section 7.2, Reporting Requirements for this Study, second bullet: 
 
• 
Other medically significant events for which expedited reporting is required include all cancers 
and pregnancies, fetal losses, IRIS events that qualify as serious adverse events, Hy’s Law liver 
toxicities, and all confirmed Grade 3 and 4 toxicities.