IMPAACT 2014 Laboratory Considerations
This document outlines laboratory considerations, processing, storage, and shipping requirements for the IMPAACT 2014 Protocol. It includes blood volume requirements, necessary supplies, and specific instructions to ensure sample integrity and accurate results. Sections cover non-standard reagents, safety evaluations, specimen processing, and more. Cohort-specific information for required supplies and materials is also provided.
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IMPAACT 2014 Laboratory Considerations LPC v 1.2 dated 09 October 2018 Protocol v 1.0 -07 Sept 2017 LoA#1 07 May 2018; LOA#2 26 April 2019 Vandana Kulkarni Laboratory Technologist Frances Whalen IMPAACT Lab Center Representative Rebecca LeBlanc Laboratory Data Manager
Laboratory Processing Chart Laboratory Processing Chart (LPC) Supplement to the IMPAACT 2014 Protocol. Details collection, processing, storage and shipping. Blood volume requirements based on typical assay requirements. EQA approved labs can use lower blood. Larger volumes are not permitted if it exceeds total defined. Some special collection materials and processing procedures may be required. Are defined and must be obtained prior to the activation. 2
Preparing for Study Evaluations Sites must ensure Availability of required tube types and volumes prior to activation. It is essential to use the correct tube volume and tube type so as not to compromise sample integrity and laboratory results. Supply for each of the PK sampling days: CRUSHED ICE/ICE BATH for whole blood; do not freeze 3
LPC Sections Protocol Required Non-Standard Reagents and Supplies Section 1: Schedule of Lab Evaluations Section 2: Safety/Clinical Laboratory Evaluations Section 3: Specimen processing Section 4: Evaluation by visit Section 5: Links and Shipping Addresses Section 6: Revision History Section 7: Appendices 4
Cohort 2 For activation there are required supplies and materials: Collections Intensive and Sparse PK - 3.5 mL K2 EDTA Na ve participant Intensive PK 2 mL K2 EDTA PK Plasma Storage 1.0 mL externally threaded cryotube Questions? Contact IMPAACT Laboratory Center Representative (fwhalen@milabcentral.org) 5
Section 1: Schedule of Laboratory Evaluations for Cohort 2 (Appendix I-B) Cohort 2: Schedule of Laboratory Evaluations d wk +2 wk LABORATORY EVALUATIONS Confirmatory HIV testing [if needed] mL] CBC with differential and platelets Weeks on Study 8 12 2 wk Screen Entry Confirm Virologi c Failure Study Visit 11 2 4 16 2 wk 242 2 wk 362 2 wk 482 2 wk Q163 4 wk Early D/C 8-13 1 -1 wk- Day 0 2 wk Visit Window [0-6 1 1 1 mL 1 mL 1 mL 1 mL 1 mL 1 mL 1 mL 1 mL 1 mL 1 mL mL 3 mL mL 3 mL 3 mL 3 mL 3 mL 3 mL 3 mL 3 mL 3 mL 3 mL 3 mL 3 mL Chemistries 2 mL (Wk 96 only) Wks 64 & 96 2 2 mL 2 mL 2 mL Lipid profiles mL X X X X X Urinalysis 4 mL Hepatitis B and C Pregnancy test4 X X X X X X 6 mL 2 mL X 6 mL X X X X 6 mL 6 mL 6 mL 6 mL 6 mL 6 mL 6 mL 6 mL 6 mL 6 mL 6 mL HIV-1 RNA 2 mL 2 mL 2 mL 2 mL 2 mL 2 mL CD4 cell counts Genotypic resistance test5 Store for resistance testing Pharmacology 2 mL5 4 mL5 6 mL6 6 mL6 21.5 mL Intensive PK sampling1 3.5 mL 22.5 mL 3.5 mL 14.5 mL 3.5 mL 18.5 mL 7 3.5 mL 7 mL Sparse PK sampling7 mL 22 mL 21.5 mL 10 mL 16.5 mL 11 mL 11 mL 22 mL 15 mL Total maximum blood volume 22 mL 13 mL 66
Footnotes Review all footnotes Can be found in SOE by each visit type Pay close attention to Details given on who is tested. Collection times. Other references. Review the visit-specific procedures in Section 6. 7
Blood Volume Considerations Cohort 1 and 2 Attempt to maximize the blood collection to meet target volumes, per the SoE. For insufficient blood draws, prioritize according to protocol specifications See Section 6.11.1. 8
Safety/Clinical Laboratory Evaluations Evaluation Tube Type Tests Hematology EDTA Complete blood count with cell differential and platelet count Electrolytes (sodium, potassium and HCO3), glucose, creatinine, lipase, phosphorus, total bilirubin, indirect bilirubin, direct bilirubin, AST, ALT, alkaline phosphatase and albumin Chemistry SST or NON Total cholesterol, HDL, LDL (calculated or measured), Triglycerides Lipid profile SST or NON Urine Dipstick urinalysis, including specific gravity, pH, blood, ketones, glucose, protein, and nitrite Urinalysis collection cup HBsAg Testing SST or NON Hepatitis B surface antigen Hepatitis C antibody SST or NON If Hepatitis C antibody is positive, perform HCV RNA PCR Confirmatory HIV Testing SST or NON or EDTA If needed perform as per Section 4.1.4 of protocol 9
Safety/Clinical Laboratory Evaluations Evaluation Tube Type Tests Urine Pregnancy Testing Note: females who have reached menarche or who are engaging in sexual activity that could lead to pregnancy only. Urine: Collection cup HCG (pregnancy test). Test must have a sensitivity of 25mIU/mL or less HCG (pregnancy test). Test must have a sensitivity of 25mIU/mL or less The total blood volume listed in the SoE at the Screening Visit accommodates collection of 1mL of blood if needed for serum pregnancy testing Serum Pregnancy Testing Note: females who have reached menarche or who are engaging in sexual activity that could lead to pregnancy only. SST or NON Lymphocyte subset (CD4+) percentages and absolute counts. Send to CLIA (US) or IQA-certified (non-US) laboratory. CD4 cell count and percentage EDTA HIV-1 RNA PCR (Abbott RealTime HIV-1 Viral Load Assay) Perform HIV-1 RNA in real time using the Abbott platform in a CLIA-certified (for US) or VQA-approved (for non-US)- lab EDTA 10
Specimen Processing Refer to Section 4 for tube types and collection volumes resistance testing. Genotyping resistance testing. Collected at Screening - ART na ve participants only. Results must be available prior to entry. Double spin blood to collect plasma. Send real-time to regional CLIA or VQA approved laboratory. 11
Specimen Processing (cont.) Storage for resistance testing: Blood collected and stored at Entry for ART na ve participants only. Double spin blood to collect plasma. Prepare plasma aliquots. Store at -70oC until shipped. May also be required at the Confirmation of Virologic Failure or Early D/C visits 12
Cohort 2 Pharmacokinetics COHORT 2 Week 2 ENTRY DAY 0 Week 1 First 10 only Week 8 Week 24 Week 36 Week 48 For DOR/3TC/TDF (Sparse PK sampling) 3.5 mL K2 EDTA Intensive PK sampling Pre dose, 1 hr, 2 hrs, 4 hrs, 12 hrs, 24hrs post dose 3.5mL K2 EDTA For DOR/3TC/TDF (Sparse PK sampling) Note: All Cohort 2 participants at Pre-dose (if possible; see protocol Section 6.3.8) 3.5 mL K2 EDTA For DOR/3TC/TDF (Sparse PK sampling) Note: All Cohort 2 participants, random collection, at Week 8 and Week 12 only 3.5 mL K2 EDTA For DOR/3TC/TDF (Sparse PK sampling) 3.5 mL K2 EDTA (Pre- dose and 0.5- 2hrs Post dose) Note: All Cohort 2 participants at Pre- dose Note: All Cohort 2 participants at Pre dose* (if possible; see protocol Section 6.3.8) and 0.5 2 hours post- dose at Week 24 and Week 48 only Store plasma for phenotypic resistance ART- Na ve only 4 mL EDTA Intensive PK sampling 1 hr, 8 hrs post dose 2.0mL K2 EDTA 13
Intensive PK Collection MK-1439, 3TC and TDF Intensive PK sample processing Immediately after collection gently and completely invert the tube 6-8 times. Place in ice bath. Process within 30 minutes of collection. Record actual time to process. NOTE: If processing will be delayed (e.g. due to home collection) tubes must remain in an ice bath and processed within 2 hours of collection. 14
Intensive PK processing For each of the time points ship: 1 x 0.5 mL plasma aliquot for MK-1439 to inVentiv Health Clinique. 2 x 0.5 mL plasma aliquots for 3TC and TDF to PMRI Analytical Laboratory. Once team requests specimens, batch ship aliquots for MK-1439 testing on dry ice to inVentiv Health Clinique. Batch ship aliquots for 3TC and TDF on dry ice to PMRI Analytical Laboratory. 15
Intensive PK Sample Labeling Note for PK plasma sample LDMS labels: Label the NUNC vials with preprinted LDMS barcoded labels. Nominal times should be added in LDMS in the time and time unit field found in primary grid. Place labels on NUNC tubes toward the top 30% of the tube so level of plasma in the tube is visible. Only one layer of label should be placed on the tube. 16
Shipping for DOR inVentiv Health Clinique Shipping procedure for Doravirine (MK-1439) Include sample inventory Completion of Commercial Invoice template is mandatory prior to shipment. Contact Bridgette Pellerin (brigitte.pellerin@inventivhealth.com) for questions on completing the Commercial Invoice form. 17
Shipping for 3TC and TDF PK SAMPLES for Lamivudine (3TC) and Tenofovir (TDF) assays - Merck Contract Lab Ship to Pharma Medica Research, Inc (PMRI) Address contained in LPC Appendix 1 Email(s): mmartell@pharmamedica.com PM@pharmamedica.com SA@pharmamedica.com Merck Contact: Robert Valesky Email: robert_valesky@merck.com Important Note: Always include Robert Valesky on all communications with the PK testing laboratory 18
Appendices 1 and 2 Samples packed and shipped Must follow appropriate IATA and local regulations. Recommend STP 320 shipper Use sufficient dry ice and UN1845 label Ship via World Courier World Courier Account #18658 Account holder: Johns Hopkins University/IMPAACT 19
Appendices (cont.) Shipments must contain: Reference line on international waybill must state IMPAACT 2014 samples Include your lab address and recipient address. Include a sample inventory list and copy of commercial invoice within each shipment. Include THREE copies of completed commercial invoice (one signed original and two copies). Email manifest to those listed previously. Follow specimen shipping days 20
Laboratory Activation Requirements All laboratories must confirm: HIV testing algorithm Access to Abbott Real-Time HIV-1 RNA PCR assay at approved laboratory Current IATA training certificates for two staff Current pediatric and adult reference ranges Obtained any required permits and S/MTAs for shipping of PK specimens 21
Laboratory Activation Requirements (cont.) US site laboratories Submit current CAP/CLIA certificates Non-US site laboratories confirm: DCLOT approval of laboratory readiness Completion of relevant IMPAACT items from DAIDS Audit Action Plan, if applicable Approval of protocol analyte list (PAL) Acceptable EQA status (pSMILE, VQA, IQA) 22
CPQA Tutorial Who will be processing the specimens? Who will be capturing on LDMS? Has the team completed the PK tutorial? Dosing time Sampling time ACTUAL time 24
Material Transfer Agreements (S/MTA) S/MTAs - institution-specific agreements Are the responsibility of the shipping laboratory Provide necessary paperwork and sign an agreement. Check with your institution if this is required. If required with inVentiv Health Clinique, contact the laboratory as soon as possible to initiate this process. Provide copy of executed MTA(s) to ILC Rep requirement for study activation 24
Upcoming LPC Change Pending final Team approval, labs may use either LDL method Section 2: Safety/Clinical Laboratory Evaluations Defer to local clinical specimen collection guidelines for tube types and collection volumes as needed. On study visits Tests eCRFs LBW10023: Chemistry/Hematology Test Results Log Evaluation Tube Type Complete blood count with cell differential and platelet count Hematology EDTA Electrolytes (sodium, potassium and HCO3), glucose, creatinine, lipase, phosphorus, total bilirubin, indirect bilirubin, direct bilirubin, AST, ALT, alkaline phosphatase and albumin LBW10023: Chemistry/Hematology Test Results Log Chemistry SST or NON LBW10023: Chemistry/Hematology Test Results Log Total cholesterol, HDL, LDL (calculated or measured), Triglycerides Lipid profile SST or NON 25
REMEMBER Protocol specific website: http://www.impaactnetwork.org/studies/IMPAACT2 014.asp 26
