CLARITY Extension Study

Primary outcomes

1. Safety Population: Percentage of Participants With at Least 1 Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE) Grade 4 Hematologic and Hepatic Toxicity

   Time frame: Baseline up to Week 120

   Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events v 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death.

2. Safety Population: Mean Change From Baseline in Absolute Lymphocyte Count, Platelet, Neutrophils and Leukocytes at Week 120

   Time frame: Baseline, Week 120

   Mean change from baseline in absolute lymphocyte count, platelet, neutrophils and leukocytes at week 120 were reported.

3. Safety Population: Mean Change From Baseline in Hemoglobin at Week 120

   Time frame: Baseline, Week 120

   Mean change from baseline in hemoglobin at Week 120 was reported.

4. Safety Population: Mean Change From Baseline in Aspartate Aminotransferase and Alanine Aminotransferase at Week 120

   Time frame: Baseline, Week 120

   Mean change from baseline in aspartate aminotransferase and alanine aminotransferase at week 120 were reported.

5. Safety Population: Mean Change From Baseline in Bilirubin at Week 120

   Time frame: Baseline, Week 120

   Mean Change From Baseline in Bilirubin at week 120 was reported.

6. Safety Population: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

   Time frame: Baseline up to Week 120

   An adverse event (AE) was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. Serious AE (SAE): Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.

7. SAFUP Analysis Set: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

   Time frame: Baseline up to Week 120

   An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. Number of participants with TEAEs included participants with both non-serious TEAEs and serious TEAEs.

8. Safety Population: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies

   Time frame: Baseline up to Week 120

   Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection are reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.

9. SAFUP Analysis Set: Number of Participants Who Developed Infections (Herpes Viral Infection, Viral Infectious Disorder and Opportunistic Infection), Infection-related Adverse Events and Malignancies

   Time frame: Baseline up to Week 120

   Number of participants who developed Herpes viral infection, Viral infectious disorder and Opportunistic infection were reported. Number of participants with infection related adverse events are the number of participants who had at least one adverse event coded to medical dictionary for regulatory activities (MedDRA) preferred terms under infection and infestation system organ class. Malignancy is defined as having at least one adverse event coded to MedDRA preferred terms under the pre-specified grouping Malignant and unspecified tumors.

10. Safety Population: Time to First Grade 3 or 4 Hematological Toxicity and Liver Toxicity

    Time frame: Baseline up to Week 120

    Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. Time to first CTCAE Grade 3 or 4 hematological or liver toxicity was analyzed by treatment group using Kaplan-Meier plots of probability of surviving toxicity-free and point estimates of percentiles. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. 10th, 20th, 25th, 50th and 75th percentiles were estimated from Kaplan-Meier survival curve.

11. Safety Population: Median Time to Recovery From Grade 3 or 4 Hematological and Hepatic Toxicity

    Time frame: Baseline up to Week 120

    Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST), Platelets and Bilirubin. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.

12. Safety Population: Mean Time to Recovery From Grade 3 or 4 Hematological and Liver Toxicity

    Time frame: Baseline up to Week 120

    Hematologic and hepatic toxicity was assessed using Common Terminology Criteria for Adverse Events (CTCAE). Hematologic and hepatic function included absolute lymphocyte count (ALC), hemoglobin level, white blood cell (WBC) count, absolute neutrophil count (ANC), platelets, alanine transaminase (ALT), aspartate transaminase (AST) and bilirubin. According to CTCAE v3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life threatening or disabling and Grade 5=Death. Time to recovery from grade 3 or 4 hematological or liver toxicity were reported: lymphocytes, platelets, neutrophils, white blood cells, hemoglobin, Alanine transaminase (ALT), Aspartate transaminase (AST) and Platelets. Recovery from a Grade 3 or 4 toxicity is defined as a return to a Grade 0 or 1.

13. Safety Population: Median Time to Nadir of Absolute Lymphocyte Count

    Time frame: Baseline up to Week 120

    Median time to nadir of absolute lymphocyte count was reported.

14. Safety Population: Mean Time to Nadir of Absolute Lymphocyte Count

    Time frame: Baseline up to Week 120

    Mean time to nadir of absolute lymphocyte count was reported.

15. Safety Population: Mean Time to Recovery From Nadir of Absolute Lymphocyte Count to Normal Value

    Time frame: Baseline up to Week 120

    Mean time to recovery from nadir of absolute lymphocyte count to normal was reported. Recovery from Nadir is defined as a return to baseline value. Normal absolute lymphocyte count is 1.02 x 10^3 cells/microliter.

16. Safety Population: Mean Change in Corrected QT (QTc) Interval From Baseline

    Time frame: Baseline, Week 5, 48, 52 and 96

    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Corrected QT (QTc) is the QT interval corrected for heart rate and RR, which is the interval between two R waves. Mean change in corrected QT (QTc) interval from baseline was reported.