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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| SAIT101 | Experimental |
| |
| MabThera® | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SAIT101 | Biological | Dose of 375mg/m2 body surface area (BSA) i.v. on Days 1, 8, 15, and 22 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day 0) to Week 28. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline (Day 0) to Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Baseline (Day 0) to dosing on Week 1 and Week 4 |
Inclusion Criteria:
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)
Low tumor burden according to The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria defined as:
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:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research site | Whittier | California | 90603 | United States | ||
| Research Site |
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).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | SAIT101 | SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4, |
| FG001 | MabThera | MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 3, 2017 | Jul 16, 2020 |
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| MabThera® |
| Biological |
Dose of 375mg/m2 body surface area (BSA) i.v. on Days 1, 8, 15, and 22 |
|
|
| 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. | Baseline (Day 0) to Week 12 and Week 28. |
| 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. | Baseline (Day 0) to Week 12 and Week 28. |
| 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. | Baseline (Day 0) to Week 12 and Week 28. |
| 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. | Baseline (Week 0)to Week 12 and Week 28. |
| 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. | Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner |
| 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). |
| Baseline (Day 0) to dosing on Week 1 and Week 4 |
| 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). | Baseline (Day 0) to dosing on Week 1 and Week 4 |
| 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). | Baseline (Day 0) to dosing on Week 1 and Week 4 |
| 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. | Baseline (Day 0) to Days 1, 8, 15, 22 and 29 |
| 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. | Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
| 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. | Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
| 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. | Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28. |
| 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. | Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28. |
| 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. | Pre-dose on Day 1 to Weeks 5, 12, 20 and 28. |
| 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. | Baseline to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
| 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) | Baseline (Day 0) to Week 28 |
| 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. | Baseline (Day 0) to Week 28 |
| Canberra |
| Australian Capital Territory |
| 2605 |
| Australia |
| Research site | Temuco | Araucania | 4810469 | Chile |
| Research site | Hradec Králové | 500 05 | Czechia |
| Research site | Prague | 128 08 | Czechia |
| Reasearch site | Prague | 15000 | Czechia |
| Research site | Libourne | Gironde | 33505 | France |
| Research site | Poitiers | Vienne | 86021 | France |
| Research site | Hamburg | 22081 | Germany |
| Research site | Budapest | 1083 | Hungary |
| Research site | San Giovanni Rotondo | Foggia | 71013 | Italy |
| Research site | Terni | 05100 | Italy |
| Research site | Mexico City | Mexico City | 03720 | Mexico |
| Research site | Pretoria | Gauteng | 0181 | South Africa |
| Research site | Busan | 49241 | South Korea |
| Research site | Seoul | 01757 | South Korea |
| Research site | Seoul | 03080 | South Korea |
| Research site | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Research site | Cadiz | 11009 | Spain |
| Research site | Madrid | 28040 | Spain |
| Research site | Ankara | 06340 | Turkey (Türkiye) |
| Research site | Istanbul | 34098 | Turkey (Türkiye) |
| Research site | Mersin | 33343 | Turkey (Türkiye) |
| Research site | Samsun | 55139 | Turkey (Türkiye) |
| Research site | Norwich | Norfolk | NR4 7UY | United Kingdom |
| Completed Treatment | Received at least one infusion of study drug. |
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| COMPLETED | Completed Week 28 (Primary Analysis cut-off) |
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| NOT COMPLETED |
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Full Analysis Set (FAS)
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| ID | Title | Description |
|---|---|---|
| BG000 | SAIT101 | SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4. |
| BG001 | MabThera | MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3 and 4. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height (cm) | Mean | Standard Deviation | cm |
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| Weight at baseline (kg) | Mean | Standard Deviation | kg |
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| Body Mass Index (kg/m^2) | Mean | Standard Deviation | kg/m^2 |
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| Body Surface Area (m^2) | Mean | Standard Deviation | m^2 |
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| Disease Duration (Years) | Disease duration was derived from initial disease diagnosis date to the date of informed consent. Note that initial disease diagnosis can be confirmed by biopsy after informed consent. | Mean | Standard Deviation | years |
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| Females of childbearing potential | Count of Participants | Participants |
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| Eastern Co-operative Oncology Group (ECOG) performance status | The ECOG score is used in the evaluation of cancer patients and can help with prognosis and management of the malignant condition because performance status is highly correlated with survival. A higher ECOG rating score generally equates to a worst outcome. ECOG scores 0 and 1 are defined as: ECOG Score 0: Asymptomatic (Fully active, able to carry on all pre-disease activities without restriction); ECOG Score 1: Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature. | Count of Participants | Participants |
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| Antidrug Antibody (ADA) Status at Baseline | Count of Participants | Participants |
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| Ann Arbor Staging | Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma and non-Hodgkin lymphoma. Stage I indicates that the cancer is located in a single region. Stage II indicates that the cancer is located in two separate regions, an affected lymph node or lymphatic organ and a second affected area. Stage III indicates that the cancer has spread to both sides of the diaphragm. Stage IV indicates diffuse or disseminated involvement of one or more extralymphatic organs. | Count of Participants | Participants |
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| Type of Ann Arbor Staging | Ann Arbor staging is the staging system for lymphomas, both in Hodgkin's lymphoma (formerly designated Hodgkin's disease) and non-Hodgkin lymphoma (abbreviated NHL). It was initially developed for Hodgkin's, but has some use in NHL. It has roughly the same function as TNM staging in solid tumors Ann Arbor Clinical Stage (CS) as obtained by doctor's examination and tests, An Arbor Pathological Stage (PS) as obtained by exploratory laparotomy with splenectomy. | Count of Participants | Participants |
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| Risk Groups According to Follicular Lymphoma International Prognostic Index (FLIP-2) Score | Follicular Lymphoma International Prognostic Index (FLIPI) score of 0 to 1 is considered "low risk" with a 10 year overall survival of 70%. A score of 2 is considered "intermediate risk" with a 10 year overall survival of 50%. Finally, a score of ≥ 3 is considered "high risk" with a 10 year overall survival of 35%. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline (Day 0) to Week 28. |
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline (Day 0) to Week 12 |
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| 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline (Day 0) to Week 12 and Week 28. |
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| 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline (Day 0) to Week 12 and Week 28. |
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| 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. | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline (Day 0) to Week 12 and Week 28. |
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| 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. | Full Analysis Dataset (FAS) | Posted | Count of Participants | Participants | Baseline (Week 0)to Week 12 and Week 28. |
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| 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. | Full Analysis Set (FAS) | Posted | Mean | Standard Deviation | Weeks | Baseline (Day 0) to time of event or up to a maximum of 32 weeks, whichever is sooner |
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| 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). | Pharmacokinetic Analysis Set (PAS) | Posted | Geometric Mean | Geometric Coefficient of Variation | H*µg/ml | Baseline (Day 0) to dosing on Week 1 and Week 4 |
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| 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). | Pharmacokinetic Analysis Set (PAS) | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/ml | Baseline (Day 0) to dosing on Week 1 and Week 4 |
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| 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). | Pharmacokinetic Analysis Set (PAS) | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Baseline (Day 0) to dosing on Week 1 and Week 4 |
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| 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). | Pharmacokinetic Analysis set (PAS) | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | Baseline (Day 0) to dosing on Week 1 and Week 4 |
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| 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. | Pharmacokinetic Analysis Set (PAS) | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/ml | Baseline (Day 0) to Days 1, 8, 15, 22 and 29 |
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| 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. | Pharmacodynamic Analysis Set (PDS) | Posted | Mean | Standard Deviation | cells/μL | Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
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| 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. | Pharmacodynamic Analysis Set (PDS) | Posted | Mean | Standard Deviation | Percent change | Baseline (Day 1) to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
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| 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. | Pharmacodynamic Analysis Set | Posted | Mean | Standard Deviation | cells*day/µL) | Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28. |
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| 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. | Pharmacodynamic Analysis Set | Posted | Mean | Standard Deviation | cells/µL | Baseline (Day 0) to Week 1, 2, 3, 4 12 and 28. |
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| 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. | Safety Analysis Set (SAS | Posted | Count of Participants | Participants | Pre-dose on Day 1 to Weeks 5, 12, 20 and 28. |
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| 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. | Safety Analysis Set (SAS) | Posted | Mean | Standard Deviation | Mg/dL | Baseline to Weeks 1, 2, 3, 4, 5, 12, 20 and 28. |
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| 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) | Full Analysis Set (FAS) | Posted | Count of Participants | Participants | Baseline (Day 0) to Week 28 |
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| 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. | Full Analysis Set (FAS) | Posted | Number | 95% Confidence Interval | percentage of participants | Baseline (Day 0) to Week 28 |
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After the participant signed the Informed Consent Form (ICF), but prior to the initiation of study drug, only Serious Adverse Events (SAEs) caused by a protocol mandated procedure should be reported (e.g. SAEs related to invasive procedures such as biopsies). All adverse events were collected for each patient from the start of the first infusion of study drug on Day 1 until the Week 28 Data-cut off.
All AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) v22.1. If an AE changed from non-SAE to be an SAE, it was treated as a new event and was counted as 2 events in the AE summary. A treatment-emergent AE (TEAE) was defined as any AE with an onset date on or after the date of the first dose of study treatment until Week 28, or the End of Study (EOS) visit, if earlier.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | SAIT101 | SAIT101: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4. | 0 | 157 | 3 | 157 | 85 | 157 |
| EG001 | MabThera | MabThera: Dose of 375 mg/m2 body surface area (BSA) intravenous on Weeks 1, 2, 3, and 4. | 1 | 158 | 4 | 158 | 70 | 158 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Sudden cardiac death | General disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Cystitis klebsiella | Infections and infestations | MedDRA v22.1 | Systematic Assessment |
| |
| Vestibular neuronitis | Infections and infestations | MedDRA v22.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v22.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA v22.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutrpopenia | Blood and lymphatic system disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA v22.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v22.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v22.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v22.1 | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Archigen Biotech Ltd | +44 (0)20 3749 5000 | info@archigenbio.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 10, 2019 | Jul 16, 2020 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069283 | Rituximab |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Czechia |
|
| United States |
|
| United Kingdom |
|
| Spain |
|
| South Korea |
|
| Turkey |
|
| Italy |
|
| Mexico |
|
| South Africa |
|
| Australia |
|
| Chile |
|
| France |
|
| Germany |
|
| Ukraine |
|
| Thailand |
|
| Serbia |
|
| Panama |
|
| India |
|
| Georgia |
|
| Guatemala |
|
| Belarus |
|
| Croatia |
|
| Egypt |
|
| Philippines |
|
| ECOG Score 1 |
|
| Negative |
|
| Not available |
|
| Stage II |
|
| Stage III |
|
| Stage IV |
|
| Pathological Stage (PS) |
|
| Intermediate Risk (2 risk factors) |
|
| High Risk (Greater than or equal to 3 risk factor |
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| Units |
|---|
| Counts |
|---|
| Participants |
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| Units | Counts |
|---|---|
| Participants |
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|
|
|
|
|
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|
| Positive |
|