3.11 Study assessments
3.11.2.9 Laboratory assessments
At all scheduled visits, except Visit E1 (Day 1), blood chemistry, hematology and urinalysis tests will be performed. The analysis of the blood samples will be carried out at the central laboratory. The contact details of the central laboratory as well as sampling, storage, and shipment procedures for completion of laboratory tests are described in the central laboratory manual. During TP1 and TP2, the central laboratory will provide all
laboratory results to the site with the exception of the results of the total white blood cell (WBC) count and total lymphocyte count. During TP3, the central laboratory will provide all laboratory results to the site, including the total WBC count and total lymphocyte count.
In the event of a clinically significant abnormality of total WBC count and/or total lymphocyte count, an alert will be communicated to the primary investigator.
Whenever a total lymphocyte count 200 cells/μL is recorded by the central laboratory, an alert will be sent to the primary investigator and the sponsor [see Appendix 1]. The primary investigator will immediately contact the patient and ask her/him to return to the site preferably within 48 hours but no later than within 1 week to repeat the test at trough level (pre-dose) by the central laboratory (unless the clinical situation mandates immediate local testing). If a local laboratory test was performed, the test results have to be captured in the CRF.
If the repeat test confirms a lymphocyte count 200 cells/μL, the study drug must be discontinued and lymphocyte count needs to be monitored at least once a week by the central laboratory (unless the clinical situation mandates immediate local testing) until the lymphocyte count has returned to ≥ 1000 cells/L or ≥ 80% of the baseline value. If a local laboratory test was performed, the follow-up test results have to be captured in the CRF.
Whenever AST or ALT ≥ 3 × the upper limit of normal range (ULN) are recorded by the central laboratory, an alert will be sent to the principal investigator and the sponsor. The sponsor will contact the principal investigator to ensure that she/he will immediately contact the patient, and ask the patient about any potential symptoms. The patient will be closely observed and will be asked to return to the site as soon as possible after the time of receipt of the alert to repeat the liver enzyme and bilirubin tests by the central laboratory (unless the clinical situation mandates immediate local testing) according to the scheme illustrated in Table 8[see Appendix 1].
Patients receiving non-live vaccination while on study treatment will have 5 mL of blood drawn prior to and at least 3 weeks after vaccination to explore changes in vaccine -specific antibody titers from pre- to post vaccination. Samples will be analyzed at the end of the study at the latest.
For WOCBP, urine pregnancy tests will be performed at the site at all visits from Visit E4 (Week 4) until EOT2 or EOT3 and at Follow-up visit E2 or FU2 using the kits provided by the central laboratory. All laboratory reports (central and local) must be signed and dated by the primary investigator or other qualified study personnel at the study site within 5 calendar days of receipt and filed with the source documentation. Any clinically significant marked laboratory abnormality must be reported as an AE and/or SAE as appropriate and must be followed until it returns to within the normal range or stabilization, or until the change is no longer clinically relevant.
If a blood sample is lost or deteriorated and could not be analyzed, the sample may need to be repeated at the investigator’s discretion.
3.11.2.9.2 Laboratory parameters
Hematology
- Red blood cell count
- Total and differential WBC counts (basophils, eosinophils, lymphocytes, monocytes, neutrophils, band forms)
- Platelet count - Hemoglobin - Hematocrit
- Mean corpuscular hemoglobin - Mean corpuscular volume
Blood chemistry
- Glucose (preferably under fasting conditions)
- ALT, AST, alkaline phosphatase, total bilirubin, lactate dehydrogenase, International Normalized Ratio (INR)
- Creatinine - Urea - Cholesterol - Triglycerides
- Sodium, potassium, chloride, calcium - Total Protein, albumin
- C-reactive protein
Urinalysis - pH - Glucose - Proteins - Blood - Leukocytes
- Bilirubin, urobilinogen
Pregnancy test
- Urine pregnancy tests will be performed at all Visits E4 to EOT2 or EOT3 and at Follow-up visit E2 or FU2, as applicable.
Female patients who interrupt the study drug because of planned pregnancy will be exempted from any protocol-mandated pregnancy tests after the first positive pregnancy test and until 30 (±5) days before study drug re-initiation.
Results will not be recorded in the CRF. In the event of pregnancy, the appropriate pregnancy notification form must be completed [see Section4.4.3].
Additional analyses in the event of infections
- The storage period of the serum sample, which was collected at Visit 2 (Baseline) of the core study and stored at the central laboratory for potential retrospective analyses of viral serology titers in the event of infections (e.g., suspected opportunistic infections) during the study, will be extended until completion of the extension study.
Analyses in case of vaccination with non-live vaccine
− Two serum samples will be taken prior to and at least 3 weeks after vaccination to be analyzed by the central laboratory for vaccine-specific antibody titers.
Pharmacokinetic and pharmacodynamic assessments