Lymphoma, Follicular
Conditions
Keywords
low tumor burden follicular lymphoma (LTBFL)
Brief summary
This is a Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the statistical equivalence of efficacy, safety and immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in asymptomatic patients with Low Tumor Burden Follicular Lymphoma.
Detailed description
This is a Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the statistical equivalence of efficacy, safety and immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in asymptomatic patients with Low Tumor Burden Follicular Lymphoma. Patients will be randomized in a 1:1 ratio to receive study drug once a week for 4 weeks, and will then be followed up for up to 52 weeks after the first dose. Randomization will be stratified by inclusion in the PK/PD sub-population and Follicular lymphoma international prognostic index 2 (FLIPI-2) score. Visits are scheduled at Weeks 1, 2, 3, and 4 (study drug infusion visits), and then at Weeks 5, 12, 20, 28, 36, and 52 (i.e., End of Study \[EOS\]). Efficacy response assessments will be performed at Weeks 12 and 28, while safety assessments will continue until end of Study (EOS). The primary objectives is to compare the efficacy of SAIT101 with rituximab licensed in the European Union (hereafter designated MabThera®, brand name in EU) when administered as a first-line immunotherapy in patients with low tumor burden follicular lymphoma (LTBFL) and the secondary objectives is to evaluate SAIT101 versus MabThera® with respect to safety and tolerability, immunogenicity and Pharmacokinetics (PK)/Pharmacodynamics (PD) in a sub-population of patients.
Interventions
Sponsors
Archigen Biotech Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with histologically-confirmed Low Tumor Burden Follicular Lymphoma, without B symptoms, Ann Arbor stage II to Non-Hodgkin's Lymphoma (NHL) (CD20+ Follicular Lymphoma of Grades 1, 2, or 3a) 2. Low tumor burden according to The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria defined as: * Normal serum lactate dehydrogenase (LDH) * No mass ≥7 cm. * Less than 3 nodal sites, each with diameter \>3 cm * No systemic or B symptoms (fever \>38°C for 3 consecutive days; recurrent, drenching night sweats; unintentional weight loss exceeding 10% body weight in the last 6 months. * No splenomegaly ≥16 cm by CT scan. * No risk of vital organ compression. * No pleural or peritoneal serous effusion. * No leukemic phase \>5,000/µL circulating tumor cells. * No cytopenias (defined as platelets \<100,000/mm3, hemoglobin \<10 g/dL, or absolute neutrophil count \<1,500/mm3). 3. Patients not previously treated for their FL, including any previous treatment for FL under clinical trials except localized radiation therapy for previous limited stage disease.
Exclusion criteria
1. Previous treatment with any chemotherapy and/or rituximab or other monoclonal antibody. 2. Prior radiotherapy completed \<28 days before study enrollment. 3. Anticipated need for concomitant administration of any other experimental drug, or a concomitant chemotherapy, anticancer hormonal therapy, radiotherapy, or immunotherapy during study participation. 4. Concomitant disease which requires continuous therapy with corticosteroids at doses equivalent to prednisolone \>20 mg/day. 5. Transformation to high-grade lymphoma secondary to previously untreated low-grade lymphoma. 6. Prior or concomitant malignancies within 5 years prior to screening, with the exceptions of non-melanoma skin cancer, adequately treated carcinoma in situ of the cervix, adequately treated breast cancer in situ, and localized prostate cancer stage T1c, provided that the patient underwent curative treatment and remains relapse free. 7. Patients with a body surface area \>3.0 m2. 8. Major surgery (excluding lymph node biopsy) within 28 days prior to randomization. 9. Primary or secondary immunodeficiency (history of, or currently active), including known history of human immunodeficiency virus (HIV) infection or positive test at screening. 10. Acute, severe infection (e.g., sepsis and opportunistic infections), or active, chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., herpes zoster). 11. Positive serological test for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb) or hepatitis C serology. 12. Confirmed current active tuberculosis (TB) 13. Central nervous system (CNS) or meningeal involvement, or cord compression by the lymphoma; history of CNS lymphoma 14. History of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the trial drug (e.g., hypersensitivity or allergy to murine products). 15. Patients who have significant cardiac disease, including but not limited to history of congestive heart failure (New York Heart Association Class III/IV; see Appendix 7), unstable angina, or uncontrolled cardiac arrhythmia. 16. Uncontrolled or severe hypertension, or cerebrovascular disease. 17. Serious underlying medical conditions that, per the Investigator's discretion, could impair the ability of the patient to participate in the trial 18. Any other co-existing medical or psychological condition(s) that will preclude participation in the study or compromise ability to give informed consent and/or comply with study procedures. 19. Treatment with any investigational medicinal product (IMP) within 4 weeks prior to initiation of 1st infusion of study drug, or treatment with a drug that has not received regulatory approval for any indication within 4 weeks or a minimum of 5 half-lives, whichever is longer, of the 1st infusion of study drug. 20. Receipt of a live/attenuated vaccine within 6 weeks prior to the screening visit. 21. Females who are pregnant, breastfeeding, or planning a pregnancy during the treatment period or within 12 months after the last infusion of study drug. 22. Patients who are investigational site staff members directly involved in the conduct of the trial, and their family members, site staff members otherwise supervised by the investigator, or patients who are Archigen employees directly involved in the conduct of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) at Week 28 | Baseline (Day 0) to Week 28. | Overall Response Rate (ORR) (Complete Response \[CR\] + Partial Response \[PR\]) at Week 28, as defined by International Working Group (IWG) criteria 2007. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) at Weeks 12 and 28 | Baseline (Day 0) to Week 12 and Week 28. | Efficacy Endpoint: Complete Response (CR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. |
| Partial Response (PR) at Weeks 12 and 28 | Baseline (Day 0) to Week 12 and Week 28. | Efficacy Endpoint: Partial Response (PR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. |
| Overall Response Rate (ORR) at Week 12 | Baseline (Day 0) to Week 12 | Overall Response Rate (ORR) = Complete Response (CR) + Partial Response (PR). Tumour assessments were assessed by central imaging review per the International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable. |
| Progressive Disease (PD) at 12 and 28 Weeks | Baseline (Week 0)to Week 12 and Week 28. | Efficacy endpoint: number of participants with Progressive Disease (PD) at 12 and 28 Weeks. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. |
| Time to Event (TTE) | Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner | Time to Event (TTE) is defined as the time of randomisation to the date when an event occurred for a maximum follow-up period of 32 weeks from baseline; an event is disease progression, death due to any cause, or the start of new treatment for follicular lymphoma, whichever comes first. |
| Stable Disease (SD) at Weeks 12 and 28 | Baseline (Day 0) to Week 12 and Week 28. | Efficacy endpoint: number of participants with Stable Disease (SD) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28. | Pharmacodynamic Endpoint: Area under the change from baseline CD19+ B-cell count time curve (AUEC) over the first dosing interval on week 1 from time 0 to the time prior to the second dose (AUEC0 168,w1), AUEC over the second dosing interval on week 2 from time 0 to the time prior to the third dose (AUEC0-168,w2), AUEC over the third dosing interval on week 3 from time 0 to the time prior to the fourth dose (AUEC0-168,w3), AUEC over the fourth dosing interval on week 4 from time 0 to 168 hours post dose (AUEC0-168,w4), AUEC from time 0 on week 1 to the time point on week 12 (AUEC0-w12), AUEC from time 0 on week 1 to the time point on week 28 (AUEC0 w28) for the change from baseline CD19+ B-cell count data. |
| Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28. | Pharmacodynamic Endpoint: Area under the change from baseline CD19+ B-cell count time curve (AUEC) over the first dosing interval on week 1 from time 0 to the time prior to the second dose (AUEC0 168,w1), AUEC over the second dosing interval on week 2 from time 0 to the time prior to the third dose (AUEC0-168,w2), AUEC over the third dosing interval on week 3 from time 0 to the time prior to the fourth dose (AUEC0-168,w3), AUEC over the fourth dosing interval on week 4 from time 0 to 168 hours post dose (AUEC0-168,w4), AUEC from time 0 on week 1 to the time point on week 12 (AUEC0-w12), AUEC from time 0 on week 1 to the time point on week 28 (AUEC0 w28) for the change from baseline CD19+ B-cell count data. The time-normalized AUEC parameters presented were calculated by dividing the respective AUEC by the time interval used to calculate the AUEC. |
| Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Pre-dose on Day 1 to Weeks 5, 12, 20 and 28. | Immunogenicity endpoint: incidence of antidrug antibodies (ADA) and Neutralising Antibody (NAb). Immunogenicity sampling was performed pre-dose at Day 1, weeks 2, 3 and 4 and at any time during the visits at weeks 5, 12, 20 and 28. |
| Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4). | Baseline (Day 0) to dosing on Week 1 and Week 4 | Pharmacokinetic endpoint: truncated area under the concentration-time curve (AUC) over the first (Day 1) and fourth (Day 22) dosing intervals (AUC0 168,w1, AUC0-168,w4). |
| Exploratory Analyses of Tumor Response and Time to Event | Baseline (Day 0) to Week 28 | Exploratory Efficacy Endpoint: Analyses of Tumor Response and Time to Event, as Determined by the Combined International Working Group (IWG) Criteria 2014, Lugano Classification and IWG Criteria 2007 (Central Assessment) (Full Analysis Set) |
| Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | Baseline (Day 0) to Week 28 | Exploratory Efficacy Endpoint: Overall Response Rate (ORR) at Week 28 by Region, Age, Gender and Anti-Drug antibody (ADA) status. ADA status through Week 28 is 'Positive' if 'Positive' at any time point, and 'Negative' if 'Negative' at all time points. The 95% CI (confidence interval) for overall response rate (ORR) was calculated using the Exact method. The results presented in this table are based on the non-responder imputed data. |
| Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | Baseline to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. | Exploratory pharmacodynamic endpoint: Mean (SD) Change from Baseline of Immunoglobulin (IgG) and immunoglobulin M (IgM) (mg/dL) by Scheduled Time for Each Treatment (Safety Analysis Set). Samples for IgG and IgM assessment were collected at Baseline and Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
| Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4). | Baseline (Day 0) to dosing on Week 1 and Week 4 | Pharmacokinetic endpoint: maximum plasma concentration (Cmax, µg/ml ) after the first dose (Week 1) and the fourth dose (week 4) (Cmax,w1, Cmax,w4). |
| Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC). | Baseline (Day 0) to dosing on Week 1 and Week 4 | Pharmacokinetic endpoint: accumulation ratio for the Area Under the Concentration Time Cure 0 to 168 hours (AUC0-168) obtained from the fourth dose (Week 4) versus the first dose (Week 1) (RAUC). Accumulation ratio, calculated for AUC0-168 as (AUC0 168,w4/AUC0 168,w1). |
| Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax). | Baseline (Day 0) to dosing on Week 1 and Week 4 | Pharmacokinetic endpoint: accumulation ratio for maximum plasma (Cmax) ratio from the fourth dose on Week 4 versus the first dose of treatment on Week 1 (RCmax). Accumulation ratio, calculated for Cmax as (Cmax,w4/Cmax,w1). |
| Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Baseline (Day 0) to Days 1, 8, 15, 22 and 29 | Pharmacokinetic endpoint: trough plasma concentration (Ctrough) during the dosing phase on Days 1, 8, 15, 22, and 29. Concentrations at predose on Days 8, 15, and 22 (µg/mL) and the time equivalent to the predose on Day 29, obtained directly from the observed concentration versus time data. |
| Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. | Pharmacodynamic Endpoint: Arithmetic mean observed change from baseline of B-lymphocyte antigen cluster of differentiation 19 (CD-19+ B-cell) counts (cells/μL) up to Week 28 by treatment. |
| Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. | Pharmacodynamic Endpoint: percent change from baseline of B-lymphocyte antigen cluster of differentiation 19 (CD-19+ B-cell) counts (cells/μL) up to Week 28 by treatment. |
Countries
Australia, Chile, Czechia, France, Germany, Hungary, Italy, Mexico, South Africa, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
One hundred and one study centres in 29 countries participated in the study. The first participant was enrolled into the study on the 18 January 2017 and the last participant completed week 28 (primary analysis cut-off) on the 17 July 2019.
Pre-assignment details
A total of 455 participants were consented for the study and 315 participants were randomized in a 1:1 ration to receive SAIT101 (n=157) versus MabThera (n=158).
Participants by arm
| Arm | Count |
|---|---|
| SAIT101 SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4. | 157 |
| MabThera MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4. | 158 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Disease Progression | 2 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | SAIT101 | Total | MabThera |
|---|---|---|---|
| Age, Continuous | 57.8 years STANDARD_DEVIATION 12.38 | 58.1 years STANDARD_DEVIATION 12.57 | 58.4 years STANDARD_DEVIATION 12.78 |
| Ann Arbor Staging Stage I | 1 Participants | 1 Participants | 0 Participants |
| Ann Arbor Staging Stage II | 39 Participants | 76 Participants | 37 Participants |
| Ann Arbor Staging Stage III | 72 Participants | 141 Participants | 69 Participants |
| Ann Arbor Staging Stage IV | 45 Participants | 97 Participants | 52 Participants |
| Antidrug Antibody (ADA) Status at Baseline Negative | 138 Participants | 286 Participants | 148 Participants |
| Antidrug Antibody (ADA) Status at Baseline Not available | 16 Participants | 24 Participants | 8 Participants |
| Antidrug Antibody (ADA) Status at Baseline Positive | 3 Participants | 5 Participants | 2 Participants |
| Body Mass Index (kg/m^2) | 26.76 kg/m^2 STANDARD_DEVIATION 4.857 | 26.71 kg/m^2 STANDARD_DEVIATION 4.905 | 26.66 kg/m^2 STANDARD_DEVIATION 4.967 |
| Body Surface Area (m^2) | 1.812 m^2 STANDARD_DEVIATION 0.2032 | 1.810 m^2 STANDARD_DEVIATION 0.2184 | 1.807 m^2 STANDARD_DEVIATION 0.2332 |
| Disease Duration (Years) | 0.937 years STANDARD_DEVIATION 2.1528 | 0.935 years STANDARD_DEVIATION 2.3726 | 0.934 years STANDARD_DEVIATION 2.5793 |
| Eastern Co-operative Oncology Group (ECOG) performance status ECOG Score 0 | 132 Participants | 250 Participants | 118 Participants |
| Eastern Co-operative Oncology Group (ECOG) performance status ECOG Score 1 | 25 Participants | 65 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants | 18 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 136 Participants | 275 Participants | 139 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 10 Participants | 22 Participants | 12 Participants |
| Females of childbearing potential | 24 Participants | 44 Participants | 20 Participants |
| Height (cm) | 165.96 cm STANDARD_DEVIATION 9.436 | 165.84 cm STANDARD_DEVIATION 10.048 | 165.71 cm STANDARD_DEVIATION 10.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 31 Participants | 61 Participants | 30 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 8 Participants | 21 Participants | 13 Participants |
| Race (NIH/OMB) White | 115 Participants | 226 Participants | 111 Participants |
| Region of Enrollment Australia | 3 participants | 8 participants | 5 participants |
| Region of Enrollment Belarus | 10 participants | 15 participants | 5 participants |
| Region of Enrollment Chile | 2 participants | 3 participants | 1 participants |
| Region of Enrollment Croatia | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Czechia | 26 participants | 50 participants | 24 participants |
| Region of Enrollment Egypt | 7 participants | 15 participants | 8 participants |
| Region of Enrollment France | 7 participants | 15 participants | 8 participants |
| Region of Enrollment Georgia | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Germany | 5 participants | 9 participants | 4 participants |
| Region of Enrollment Guatemala | 2 participants | 5 participants | 3 participants |
| Region of Enrollment Hungary | 4 participants | 13 participants | 9 participants |
| Region of Enrollment India | 16 participants | 32 participants | 16 participants |
| Region of Enrollment Italy | 13 participants | 21 participants | 8 participants |
| Region of Enrollment Mexico | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Panama | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Philippines | 1 participants | 2 participants | 1 participants |
| Region of Enrollment Serbia | 1 participants | 4 participants | 3 participants |
| Region of Enrollment South Africa | 6 participants | 8 participants | 2 participants |
| Region of Enrollment South Korea | 10 participants | 22 participants | 12 participants |
| Region of Enrollment Spain | 18 participants | 40 participants | 22 participants |
| Region of Enrollment Thailand | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Turkey | 9 participants | 18 participants | 9 participants |
| Region of Enrollment Ukraine | 5 participants | 13 participants | 8 participants |
| Region of Enrollment United Kingdom | 3 participants | 4 participants | 1 participants |
| Region of Enrollment United States | 2 participants | 5 participants | 3 participants |
| Risk Groups According to Follicular Lymphoma International Prognostic Index (FLIP-2) Score High Risk (Greater than or equal to 3 risk factor | 15 Participants | 29 Participants | 14 Participants |
| Risk Groups According to Follicular Lymphoma International Prognostic Index (FLIP-2) Score Intermediate Risk (2 risk factors) | 40 Participants | 81 Participants | 41 Participants |
| Risk Groups According to Follicular Lymphoma International Prognostic Index (FLIP-2) Score Low Risk (0 to 1 risk factors) | 102 Participants | 205 Participants | 103 Participants |
| Sex: Female, Male Female | 86 Participants | 174 Participants | 88 Participants |
| Sex: Female, Male Male | 71 Participants | 141 Participants | 70 Participants |
| Type of Ann Arbor Staging Clinical Stage (CS) | 144 Participants | 284 Participants | 140 Participants |
| Type of Ann Arbor Staging Pathological Stage (PS) | 13 Participants | 31 Participants | 18 Participants |
| Weight at baseline (kg) | 73.80 kg STANDARD_DEVIATION 15.107 | 73.67 kg STANDARD_DEVIATION 15.85 | 73.54 kg STANDARD_DEVIATION 16.602 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 157 | 1 / 158 |
| other Total, other adverse events | 85 / 157 | 70 / 158 |
| serious Total, serious adverse events | 3 / 157 | 4 / 158 |
Outcome results
Primary
Overall Response Rate (ORR) at Week 28
Overall Response Rate (ORR) (Complete Response \[CR\] + Partial Response \[PR\]) at Week 28, as defined by International Working Group (IWG) criteria 2007. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable.
Time frame: Baseline (Day 0) to Week 28.
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAIT101 | Overall Response Rate (ORR) at Week 28 | 66.3 percentage of participants |
| MabThera | Overall Response Rate (ORR) at Week 28 | 70.6 percentage of participants |
Comparison: Adjusted Difference Rate (%) in Overall Response Rate (ORR) of SAIT101 versus MabThera at Week 28.95% CI: [-14.8, 6.35]
Secondary
Complete Response (CR) at Weeks 12 and 28
Efficacy Endpoint: Complete Response (CR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
Time frame: Baseline (Day 0) to Week 12 and Week 28.
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAIT101 | Complete Response (CR) at Weeks 12 and 28 | CR at Week 12 | 39 Participants |
| SAIT101 | Complete Response (CR) at Weeks 12 and 28 | CR at Week 28 | 51 Participants |
| MabThera | Complete Response (CR) at Weeks 12 and 28 | CR at Week 28 | 50 Participants |
| MabThera | Complete Response (CR) at Weeks 12 and 28 | CR at Week 12 | 37 Participants |
Secondary
Overall Response Rate (ORR) at Week 12
Overall Response Rate (ORR) = Complete Response (CR) + Partial Response (PR). Tumour assessments were assessed by central imaging review per the International Working Group (IWG) Criteria 2007. The 95% CI for overall response rate (ORR) was calculated using the Exact method and combined using the Rubin's rule when multiple imputation was applicable.
Time frame: Baseline (Day 0) to Week 12
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SAIT101 | Overall Response Rate (ORR) at Week 12 | 59.6 percentage of participants |
| MabThera | Overall Response Rate (ORR) at Week 12 | 70.0 percentage of participants |
Comparison: Adjusted Difference Rate of Overall Response Rate (ORR) of SAIT101 versus MabThera at Week 12.95% CI: [-20.92, 0.61]
Secondary
Partial Response (PR) at Weeks 12 and 28
Efficacy Endpoint: Partial Response (PR) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
Time frame: Baseline (Day 0) to Week 12 and Week 28.
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAIT101 | Partial Response (PR) at Weeks 12 and 28 | PR at Week 12 | 48 Participants |
| SAIT101 | Partial Response (PR) at Weeks 12 and 28 | PR at Week 28 | 47 Participants |
| MabThera | Partial Response (PR) at Weeks 12 and 28 | PR at Week 12 | 68 Participants |
| MabThera | Partial Response (PR) at Weeks 12 and 28 | PR at Week 28 | 53 Participants |
Secondary
Progressive Disease (PD) at 12 and 28 Weeks
Efficacy endpoint: number of participants with Progressive Disease (PD) at 12 and 28 Weeks. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
Time frame: Baseline (Week 0)to Week 12 and Week 28.
Population: Full Analysis Dataset (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAIT101 | Progressive Disease (PD) at 12 and 28 Weeks | PD at Week 12 | 4 Participants |
| SAIT101 | Progressive Disease (PD) at 12 and 28 Weeks | PD at Week 28 | 20 Participants |
| MabThera | Progressive Disease (PD) at 12 and 28 Weeks | PD at Week 12 | 1 Participants |
| MabThera | Progressive Disease (PD) at 12 and 28 Weeks | PD at Week 28 | 11 Participants |
Secondary
Stable Disease (SD) at Weeks 12 and 28
Efficacy endpoint: number of participants with Stable Disease (SD) at Weeks 12 and 28. Tumour assessments were assessed by central imaging review per International Working Group (IWG) Criteria 2007.
Time frame: Baseline (Day 0) to Week 12 and Week 28.
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAIT101 | Stable Disease (SD) at Weeks 12 and 28 | SD at Week 12 | 50 Participants |
| SAIT101 | Stable Disease (SD) at Weeks 12 and 28 | SD at Week 28 | 22 Participants |
| MabThera | Stable Disease (SD) at Weeks 12 and 28 | SD at Week 12 | 39 Participants |
| MabThera | Stable Disease (SD) at Weeks 12 and 28 | SD at Week 28 | 27 Participants |
Secondary
Time to Event (TTE)
Time to Event (TTE) is defined as the time of randomisation to the date when an event occurred for a maximum follow-up period of 32 weeks from baseline; an event is disease progression, death due to any cause, or the start of new treatment for follicular lymphoma, whichever comes first.
Time frame: Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner
Population: Full Analysis Set (FAS)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Time to Event (TTE) | 23.50 Weeks | Standard Deviation 7.5 |
| MabThera | Time to Event (TTE) | 24.08 Weeks | Standard Deviation 6.767 |
Comparison: Time to Event (TTE) Hazard Ratio (HR) of SAIT101:MabThera. The TTE is defined as the time from the date of randomization to the date when an event occurs; an event is disease progression as assessed by Investigator, death due to any cause, or the start of new treatment, whichever comes first.95% CI: [0.853, 3.482]
Other Pre-specified
Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC).
Pharmacokinetic endpoint: accumulation ratio for the Area Under the Concentration Time Cure 0 to 168 hours (AUC0-168) obtained from the fourth dose (Week 4) versus the first dose (Week 1) (RAUC). Accumulation ratio, calculated for AUC0-168 as (AUC0 168,w4/AUC0 168,w1).
Time frame: Baseline (Day 0) to dosing on Week 1 and Week 4
Population: Pharmacokinetic Analysis Set (PAS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC). | 2.075 Ratio | Geometric Coefficient of Variation 17.2 |
| MabThera | Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC). | 2.137 Ratio | Geometric Coefficient of Variation 21 |
Other Pre-specified
Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax).
Pharmacokinetic endpoint: accumulation ratio for maximum plasma (Cmax) ratio from the fourth dose on Week 4 versus the first dose of treatment on Week 1 (RCmax). Accumulation ratio, calculated for Cmax as (Cmax,w4/Cmax,w1).
Time frame: Baseline (Day 0) to dosing on Week 1 and Week 4
Population: Pharmacokinetic Analysis set (PAS)
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| SAIT101 | Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax). | 1.706 Ratio | Geometric Coefficient of Variation 23.2 |
| MabThera | Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax). | 1.671 Ratio | Geometric Coefficient of Variation 21 |
Other Pre-specified
Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
Pharmacodynamic Endpoint: Area under the change from baseline CD19+ B-cell count time curve (AUEC) over the first dosing interval on week 1 from time 0 to the time prior to the second dose (AUEC0 168,w1), AUEC over the second dosing interval on week 2 from time 0 to the time prior to the third dose (AUEC0-168,w2), AUEC over the third dosing interval on week 3 from time 0 to the time prior to the fourth dose (AUEC0-168,w3), AUEC over the fourth dosing interval on week 4 from time 0 to 168 hours post dose (AUEC0-168,w4), AUEC from time 0 on week 1 to the time point on week 12 (AUEC0-w12), AUEC from time 0 on week 1 to the time point on week 28 (AUEC0 w28) for the change from baseline CD19+ B-cell count data.
Time frame: Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28.
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w1 (cells*day/µL) | -946.0 cells*day/µL) | Standard Deviation 830.29 |
| SAIT101 | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w2 (cells*day/µL) | -987.2 cells*day/µL) | Standard Deviation 997.57 |
| SAIT101 | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w3 (cells*day/µL) | -944.8 cells*day/µL) | Standard Deviation 910.79 |
| SAIT101 | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w4 (cells*day/µL) | -956.3 cells*day/µL) | Standard Deviation 728.52 |
| SAIT101 | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-w12 (cells*day/µL) | 11330 cells*day/µL) | Standard Deviation 9854.1 |
| SAIT101 | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-w28 (cells*day/µL) | -26370 cells*day/µL) | Standard Deviation 22794 |
| MabThera | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-w12 (cells*day/µL) | -12280 cells*day/µL) | Standard Deviation 10185 |
| MabThera | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w1 (cells*day/µL) | -1000 cells*day/µL) | Standard Deviation 891.82 |
| MabThera | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w4 (cells*day/µL) | -1196 cells*day/µL) | Standard Deviation 1153.7 |
| MabThera | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w2 (cells*day/µL) | -1104 cells*day/µL) | Standard Deviation 947.68 |
| MabThera | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-w28 (cells*day/µL) | -28860 cells*day/µL) | Standard Deviation 25439 |
| MabThera | Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w3 (cells*day/µL) | -1073 cells*day/µL) | Standard Deviation 930.95 |
Other Pre-specified
Exploratory Analyses of Tumor Response and Time to Event
Exploratory Efficacy Endpoint: Analyses of Tumor Response and Time to Event, as Determined by the Combined International Working Group (IWG) Criteria 2014, Lugano Classification and IWG Criteria 2007 (Central Assessment) (Full Analysis Set)
Time frame: Baseline (Day 0) to Week 28
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SAIT101 | Exploratory Analyses of Tumor Response and Time to Event | Complete Response (CR) | 53 Participants |
| SAIT101 | Exploratory Analyses of Tumor Response and Time to Event | Partial Response (PR) | 47 Participants |
| SAIT101 | Exploratory Analyses of Tumor Response and Time to Event | Stable Disease (SD) | 21 Participants |
| SAIT101 | Exploratory Analyses of Tumor Response and Time to Event | Progressive Disease (PD) | 19 Participants |
| SAIT101 | Exploratory Analyses of Tumor Response and Time to Event | Unknown (UKN) | 1 Participants |
| SAIT101 | Exploratory Analyses of Tumor Response and Time to Event | No Evidence of Disease (NED) | 4 Participants |
| MabThera | Exploratory Analyses of Tumor Response and Time to Event | Unknown (UKN) | 2 Participants |
| MabThera | Exploratory Analyses of Tumor Response and Time to Event | Complete Response (CR) | 50 Participants |
| MabThera | Exploratory Analyses of Tumor Response and Time to Event | Progressive Disease (PD) | 11 Participants |
| MabThera | Exploratory Analyses of Tumor Response and Time to Event | Partial Response (PR) | 55 Participants |
| MabThera | Exploratory Analyses of Tumor Response and Time to Event | No Evidence of Disease (NED) | 1 Participants |
| MabThera | Exploratory Analyses of Tumor Response and Time to Event | Stable Disease (SD) | 25 Participants |
Other Pre-specified
Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit
Immunogenicity endpoint: incidence of antidrug antibodies (ADA) and Neutralising Antibody (NAb). Immunogenicity sampling was performed pre-dose at Day 1, weeks 2, 3 and 4 and at any time during the visits at weeks 5, 12, 20 and 28.
Time frame: Pre-dose on Day 1 to Weeks 5, 12, 20 and 28.
Population: Safety Analysis Set (SAS
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 NAb | Negative | 3 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) ADA | Negative | 138 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) ADA | Positive | 3 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) NAb | Negative | 3 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 ADA | Negative | 143 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 ADA | Positive | 1 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 NAb | Negative | 1 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 ADA | Negative | 138 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 ADA | Positive | 5 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 NAb | Negative | 5 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 ADA | Negative | 145 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 ADA | Positive | 2 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 NAb | Negative | 2 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 ADA | Negative | 139 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 ADA | Positive | 2 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 NAb | Negative | 2 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 ADA | Negative | 137 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 ADA | Positive | 3 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 ADA | Negative | 131 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 ADA | Positive | 7 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 NAb | Negative | 7 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 NAb | Positive | 0 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 28 ADA | Negative | 126 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 28 ADA | Positive | 10 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 29 NAb | Negative | 9 Participants |
| SAIT101 | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 29 NAb | Positive | 1 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 29 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 ADA | Negative | 144 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) ADA | Negative | 148 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 ADA | Negative | 145 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) ADA | Positive | 2 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 28 ADA | Negative | 129 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) NAb | Negative | 2 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 ADA | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 1 (Baseline) NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 ADA | Positive | 4 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 ADA | Negative | 152 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 NAb | Negative | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 ADA | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 29 NAb | Negative | 16 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 NAb | Negative | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 ADA | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 2 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 5 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 ADA | Negative | 148 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 NAb | Negative | 4 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 ADA | Positive | 2 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 ADA | Negative | 144 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 NAb | Negative | 2 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 28 ADA | Positive | 16 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 3 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 NAb | Negative | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 ADA | Negative | 149 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 20 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 ADA | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 12 NAb | Positive | 0 Participants |
| MabThera | Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit | Week 4 NAb | Negative | 0 Participants |
Other Pre-specified
Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4).
Pharmacokinetic endpoint: maximum plasma concentration (Cmax, µg/ml ) after the first dose (Week 1) and the fourth dose (week 4) (Cmax,w1, Cmax,w4).
Time frame: Baseline (Day 0) to dosing on Week 1 and Week 4
Population: Pharmacokinetic Analysis Set (PAS)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4). | Cmax, week 1 | 199.3 µg/ml | Geometric Coefficient of Variation 22.1 |
| SAIT101 | Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4). | Cmax, week 4 | 333.6 µg/ml | Geometric Coefficient of Variation 22.8 |
| MabThera | Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4). | Cmax, week 1 | 200.6 µg/ml | Geometric Coefficient of Variation 27.5 |
| MabThera | Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4). | Cmax, week 4 | 336.2 µg/ml | Geometric Coefficient of Variation 20.2 |
Comparison: Statistical Comparison: geometric least square (GLS) Mean Ratio (90% CI) (%) of SAIT101 versus MabThera maximum plasma concentration at Week 1 (Cmax,w1) (h×µg/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment.90% CI: [90.85, 103.4]
Comparison: Statistical Comparison: geometric least square (GLS) Mean Ratio (90% CI) (%) of SAIT101 versus MabThera maximum plasma concentration at Week 4 (Cmax,w1) (h×µg/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment90% CI: [92.96, 105.92]
Other Pre-specified
Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
Pharmacodynamic Endpoint: Area under the change from baseline CD19+ B-cell count time curve (AUEC) over the first dosing interval on week 1 from time 0 to the time prior to the second dose (AUEC0 168,w1), AUEC over the second dosing interval on week 2 from time 0 to the time prior to the third dose (AUEC0-168,w2), AUEC over the third dosing interval on week 3 from time 0 to the time prior to the fourth dose (AUEC0-168,w3), AUEC over the fourth dosing interval on week 4 from time 0 to 168 hours post dose (AUEC0-168,w4), AUEC from time 0 on week 1 to the time point on week 12 (AUEC0-w12), AUEC from time 0 on week 1 to the time point on week 28 (AUEC0 w28) for the change from baseline CD19+ B-cell count data. The time-normalized AUEC parameters presented were calculated by dividing the respective AUEC by the time interval used to calculate the AUEC.
Time frame: Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28.
Population: Pharmacodynamic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w2, normalized (cells/µL) | -137.1 cells/µL | Standard Deviation 123.43 |
| SAIT101 | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w4, normalized (cells/µL) | -138.7 cells/µL | Standard Deviation 121.62 |
| SAIT101 | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w3, normalized (cells/µL) | -134.3 cells/µL | Standard Deviation 121.75 |
| SAIT101 | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-w12, normalized (cells/µL) | -143.0 cells/µL | Standard Deviation 121.38 |
| SAIT101 | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w1, normalized (cells/µL) | -135.0 cells/µL | Standard Deviation 118.88 |
| MabThera | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-w12, normalized (cells/µL) | -158.7 cells/µL | Standard Deviation 133.02 |
| MabThera | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w1, normalized (cells/µL) | -142.1 cells/µL | Standard Deviation 125.23 |
| MabThera | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w2, normalized (cells/µL) | -155.1 cells/µL | Standard Deviation 133.38 |
| MabThera | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w3, normalized (cells/µL) | -155.7 cells/µL | Standard Deviation 135.47 |
| MabThera | Normalized Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval | AUEC0-168,w4, normalized (cells/µL) | -159.2 cells/µL | Standard Deviation 136.55 |
Comparison: Statistical Comparison of CD19+ B-cell Pharmacodynamic Parameters (Pharmacodynamic Analysis Set). Area under the pharmacodynamic time effect curve from baseline (Time 0) to Week 1 (AUEC0-168,w1), normalized (cells/µL). The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-31, 45.4]
Comparison: Statistical Comparison of CD19+ B-cell Pharmacodynamic Parameters (Pharmacodynamic Analysis Set). Area under the pharmacodynamic time effect curve from baseline (Time 0) to Week 2 (AUEC0-168,w2), normalized (cells/µL). The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-21.6, 57.6]
Comparison: Statistical Comparison of CD19+ B-cell Pharmacodynamic Parameters (Pharmacodynamic Analysis Set). Area under the pharmacodynamic time effect curve from baseline (Time 0) to Week 3 (AUEC0-168,w3), normalized (cells/µL). The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-18.3, 61]
Comparison: Statistical Comparison of CD19+ B-cell Pharmacodynamic Parameters (Pharmacodynamic Analysis Set). Area under the pharmacodynamic time effect curve from baseline (Time 0) to Week 4 (AUEC0-168,w4), normalized (cells/µL). The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-19.3, 60.2]
Comparison: Statistical Comparison of CD19+ B-cell Pharmacodynamic Parameters (Pharmacodynamic Analysis Set). Area under the pharmacodynamic time effect curve from baseline (Time 0) to Week 12 (AUEC0-168,w12), normalized (cells/µL). The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-23.1, 54.6]
Comparison: Statistical Comparison of CD19+ B-cell Pharmacodynamic Parameters (Pharmacodynamic Analysis Set). Area under the pharmacodynamic time effect curve from baseline (Time 0) to Week 28 (AUEC0-168,w28), normalized (cells/µL). The statistical comparison of the between treatments is based on an analysis of covariance (ANOVA) model with fixed effect for treatment and a covariate for baseline value.90% CI: [-26, 51.8]
Other Pre-specified
Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
Pharmacodynamic Endpoint: Arithmetic mean observed change from baseline of B-lymphocyte antigen cluster of differentiation 19 (CD-19+ B-cell) counts (cells/μL) up to Week 28 by treatment.
Time frame: Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
Population: Pharmacodynamic Analysis Set (PDS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 1 Mean Change from Baseline | -128.0 cells/μL | Standard Deviation 115.71 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 2 Mean Change from Baseline | -144.1 cells/μL | Standard Deviation 123.34 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 3 Mean Change from Baseline | -142.8 cells/μL | Standard Deviation 122.63 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 4 Mean Change from Baseline | -141.5 cells/μL | Standard Deviation 122.92 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 5 Mean Change from Baseline | -140.0 cells/μL | Standard Deviation 120.74 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 12 Mean Change from Baseline | -144.2 cells/μL | Standard Deviation 122.09 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 20 Mean Change from Baseline | -140.8 cells/μL | Standard Deviation 117.98 |
| SAIT101 | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 28 Mean Change from Baseline | -136.6 cells/μL | Standard Deviation 122.8 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 28 Mean Change from Baseline | -148.2 cells/μL | Standard Deviation 134.79 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 1 Mean Change from Baseline | -141.6 cells/μL | Standard Deviation 120.9 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 5 Mean Change from Baseline | -158.5 cells/μL | Standard Deviation 134.27 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 2 Mean Change from Baseline | -146.8 cells/μL | Standard Deviation 138.76 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 20 Mean Change from Baseline | -159.5 cells/μL | Standard Deviation 135.63 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 3 Mean Change from Baseline | -157.4 cells/μL | Standard Deviation 102.03 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 12 Mean Change from Baseline | -160.1 cells/μL | Standard Deviation 134.09 |
| MabThera | Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 4 Mean Change from Baseline | -141.2 cells/μL | Standard Deviation 102.03 |
Other Pre-specified
Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time
Exploratory pharmacodynamic endpoint: Mean (SD) Change from Baseline of Immunoglobulin (IgG) and immunoglobulin M (IgM) (mg/dL) by Scheduled Time for Each Treatment (Safety Analysis Set). Samples for IgG and IgM assessment were collected at Baseline and Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
Time frame: Baseline to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
Population: Safety Analysis Set (SAS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 2 | -0.21 Mg/dL | Standard Deviation 132.687 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 3 | -17.08 Mg/dL | Standard Deviation 157.848 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 4 | -36.31 Mg/dL | Standard Deviation 132.326 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 5 | -34.62 Mg/dL | Standard Deviation 162.748 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 12 | -28.15 Mg/dL | Standard Deviation 159.898 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 20 | -26.86 Mg/dL | Standard Deviation 189.937 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 28 | -19.33 Mg/dL | Standard Deviation 200.69 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 2 | 0.34 Mg/dL | Standard Deviation 18.018 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 3 | 0.87 Mg/dL | Standard Deviation 25.092 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 4 | 0.64 Mg/dL | Standard Deviation 31.836 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 5 | -1.91 Mg/dL | Standard Deviation 29.521 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 12 | 8.02 Mg/dL | Standard Deviation 37.876 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 20 | -12.94 Mg/dL | Standard Deviation 46.966 |
| SAIT101 | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 28 | -22.08 Mg/dL | Standard Deviation 29.2 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 5 | -2.02 Mg/dL | Standard Deviation 21.651 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 2 | -14.79 Mg/dL | Standard Deviation 132.64 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 2 | 4.60 Mg/dL | Standard Deviation 28.273 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 3 | -30.04 Mg/dL | Standard Deviation 124.814 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 20 | -14.35 Mg/dL | Standard Deviation 26.012 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 4 | -34.64 Mg/dL | Standard Deviation 156.79 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 3 | 2.12 Mg/dL | Standard Deviation 32.569 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 5 | -38.21 Mg/dL | Standard Deviation 170.758 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 12 | 9.12 Mg/dL | Standard Deviation 21.671 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 12 | -2.30 Mg/dL | Standard Deviation 202.017 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 4 | 0.03 Mg/dL | Standard Deviation 30.009 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 20 | -22.40 Mg/dL | Standard Deviation 173.42 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgM Week 28 | -20.85 Mg/dL | Standard Deviation 37.475 |
| MabThera | Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time | IgG Week 28 | 8.70 Mg/dL | Standard Deviation 238.309 |
Other Pre-specified
Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
Pharmacodynamic Endpoint: percent change from baseline of B-lymphocyte antigen cluster of differentiation 19 (CD-19+ B-cell) counts (cells/μL) up to Week 28 by treatment.
Time frame: Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28.
Population: Pharmacodynamic Analysis Set (PDS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 2 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 1 % Change from Baseline | -89.02 Percent change | Standard Deviation 26.324 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 3 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 4 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 5 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 12 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 20 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| SAIT101 | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 28 % Change from Baseline | -97.42 Percent change | Standard Deviation 12.749 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 28 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 5 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 1 % Change from Baseline | -95.58 Percent change | Standard Deviation 8.294 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 2 % Change from Baseline | -94.62 Percent change | Standard Deviation 1.23 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 20 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 3 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 12 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
| MabThera | Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28 | Week 4 % Change from Baseline | -100.00 Percent change | Standard Deviation 0 |
Other Pre-specified
Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28.
Exploratory Efficacy Endpoint: Overall Response Rate (ORR) at Week 28 by Region, Age, Gender and Anti-Drug antibody (ADA) status. ADA status through Week 28 is 'Positive' if 'Positive' at any time point, and 'Negative' if 'Negative' at all time points. The 95% CI (confidence interval) for overall response rate (ORR) was calculated using the Exact method. The results presented in this table are based on the non-responder imputed data.
Time frame: Baseline (Day 0) to Week 28
Population: Full Analysis Set (FAS)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR European Union (%) | 68.5 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Other Region (%) | 54.8 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Age 10-60 years (%) | 58.6 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Age >60 years (%) | 67.1 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Gender Female (%) | 72.1 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Gender Male (%) | 50.7 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR ADA Positive (%) | 42.1 percentage of participants |
| SAIT101 | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR ADA Negative (%) | 65.4 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR ADA Negative (%) | 66.7 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR European Union (%) | 70.2 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Gender Female (%) | 67.0 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Other Region (%) | 57.8 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR ADA Positive (%) | 57.1 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Age 10-60 years (%) | 70.6 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Gender Male (%) | 62.9 percentage of participants |
| MabThera | Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28. | ORR Age >60 years (%) | 58.9 percentage of participants |
Comparison: Exploratory statistical analysis: Comparison of Overall Response Rate (ORR) by Region (European Union / Other). The interaction p-value for the Region subgroup was calculated based upon the full set of data, and based on a Cochran Mantel Haenszel (CMH) model including treatment, and applicable stratification covariate.p-value: 0.587Gail-Simon
Comparison: Exploratory statistical analysis. Overall Response Rate by Age Group (18-60 years and \>60 years). The interaction p-value for the Age subgroup was calculated based upon the full set of data, and based on a Cochran Mantel Haenszel (CMH) model including treatment, and applicable stratification covariate.p-value: 0.421Gail-Simon
Comparison: Exploratory statistical analysis. Comparison of Overall Response Rate (ORR) by Gender (Male / Female). The interaction p-value for the Gender subgroup was calculated based upon the full set of data, and based on a Cochran Mantel Haenszel (CMH) model including treatment, and applicable stratification covariate. The p-value was calculated using Gail-Simon Test for Qualitative Interactions.p-value: 0.288Gail-Simon
Comparison: Exploratory statistical analysis. Comparison of Overall Response Rate (ORR) by Anti-drug Antibody (ADA) status (Positive / Negative). The interaction p-value for the ADA subgroup was calculated based upon the full set of data, and based on a Cochran Mantel Haenszel (CMH) model including treatment, and applicable stratification covariate.p-value: 0.588Gail-Wilson
Other Pre-specified
Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough).
Pharmacokinetic endpoint: trough plasma concentration (Ctrough) during the dosing phase on Days 1, 8, 15, 22, and 29. Concentrations at predose on Days 8, 15, and 22 (µg/mL) and the time equivalent to the predose on Day 29, obtained directly from the observed concentration versus time data.
Time frame: Baseline (Day 0) to Days 1, 8, 15, 22 and 29
Population: Pharmacokinetic Analysis Set (PAS)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 8 | 60.60 µg/ml | Geometric Coefficient of Variation 45.5 |
| SAIT101 | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 15 | 108.1 µg/ml | Geometric Coefficient of Variation 26 |
| SAIT101 | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 22 | 143 µg/ml | Geometric Coefficient of Variation 23.8 |
| SAIT101 | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 29 | 181.7 µg/ml | Geometric Coefficient of Variation 22.1 |
| MabThera | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 29 | 190.4 µg/ml | Geometric Coefficient of Variation 26.1 |
| MabThera | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 8 | 61.00 µg/ml | Geometric Coefficient of Variation 43.4 |
| MabThera | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 22 | 143.3 µg/ml | Geometric Coefficient of Variation 30 |
| MabThera | Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough). | Ctrough Day 15 | 107.3 µg/ml | Geometric Coefficient of Variation 32 |
Comparison: Statistical Comparison: geometric least square (GLS) Mean Ratio (90% CI) (%) of SAIT101 versus MabThera trough plasma concentration at the end of the dosing period (Day 29) (Ctrough,d29) (µg/mL) . The statistical comparison of the log-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment90% CI: [88.85, 102.55]
Other Pre-specified
Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4).
Pharmacokinetic endpoint: truncated area under the concentration-time curve (AUC) over the first (Day 1) and fourth (Day 22) dosing intervals (AUC0 168,w1, AUC0-168,w4).
Time frame: Baseline (Day 0) to dosing on Week 1 and Week 4
Population: Pharmacokinetic Analysis Set (PAS)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| SAIT101 | Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4). | AUC0-168, week 1 | 20140 H*µg/ml | Geometric Coefficient of Variation 18.7 |
| SAIT101 | Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4). | AUC0-168, week 4 | 41290 H*µg/ml | Geometric Coefficient of Variation 19 |
| MabThera | Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4). | AUC0-168, week 1 | 19860 H*µg/ml | Geometric Coefficient of Variation 18.3 |
| MabThera | Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4). | AUC0-168, week 4 | 42600 H*µg/ml | Geometric Coefficient of Variation 19.4 |
Comparison: Statistical Comparison: geometric least square (GLS) Mean Ratio (90% Confidence Interval (CI)) (%) of SAIT101 versus MabThera Area Under the Concentration time Curve Day 0 to Week 1 (AUC0-168,w1) (h×µg/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment.90% CI: [95.86, 107.24]
Comparison: Statistical Comparison: geometric least square (GLS) Mean Ratio (90% Confidence Interval (CI)) %) of SAIT101 versus MabThera Area Under the Concentration time Cure Day 0 to Week 4 (AUC0-168,w4) (h×µg/mL). The statistical comparison of the loge-transformed primary parameters between treatments is based on an analysis of variance model with fixed effect for treatment.90% CI: [90.85, 103.4]