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CompletedNCT02809053RAMO-2Updated Oct 8, 2020Results posted

A Randomized, Double-blind, Multi-center, Multi-national Trial to Evaluate the Efficacy, Safety, and Immunogenicity of SAIT101 Versus Rituximab as a First-line Immunotherapy Treatment in Patients With Low Tumor Burden Follicular Lymphoma

A Phase 3 interventional study of SAIT101 and MabThera® in Lymphoma, Follicular, sponsored by Archigen Biotech Limited. Completed at 25 sites in 14 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-10-08.

Sponsored by Archigen Biotech Limited · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
315
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Lymphoma, Follicular

Keywords

  • low tumor burden follicular lymphoma (LTBFL)
03

In context

Lymphoma

5,579 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 315 is above the median of 40 across 4,509 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

Archigen Biotech Limited is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
315 participants (actual)

Study arms

  • Experimental
    SAIT101

    Biological: SAIT101

  • Active comparator
    MabThera®

    Biological: MabThera®

Interventions

  • BiologicalSAIT101

    Dose of 375mg/m2 body surface area (BSA) i.v. on Days 1, 8, 15, and 22

  • BiologicalMabThera®

    Dose of 375mg/m2 body surface area (BSA) i.v. on Days 1, 8, 15, and 22

    Also known as: Rituximab

06

What researchers measure

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

Other outcomes

  1. 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

  2. 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

  3. 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

  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).

    Time frame: Baseline (Day 0) to dosing on Week 1 and Week 4

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

07

Results

Posted Oct 8, 2020

Participant flow

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.

Participant flow — Overall Study
MilestoneSAIT101MabThera
Started157158
Completed treatment156156
Completed150152
Not completed76
Withdrew: Death01
Withdrew: Lost to follow-up31
Withdrew: Withdrawal by subject23
Withdrew: Disease progression21

Outcome measures

PrimaryOverall 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.
Reported as:
Number · percentage of participants
Overall Response Rate (ORR) at Week 28
percentage of participantsSAIT101MabThera
Overall Response Rate (ORR) at Week 2866.3 (58.64 to 73.87)70.6 (63.21 to 77.97)
Statistical analysis
  • SAIT101 vs MabThera · Adjusted difference rate (%): -4.2 · 95% CI -14.80 to 6.35Comparison: SAIT101 versus MabThera.
SecondaryOverall 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
Reported as:
Number · percentage of participants
Overall Response Rate (ORR) at Week 12
percentage of participantsSAIT101MabThera
Overall Response Rate (ORR) at Week 1259.6 (51.16 to 67.62)70.0 (61.99 to 77.20)
Statistical analysis
  • SAIT101 vs MabThera · Adjusted difference rate: -10.3 · 95% CI -20.92 to 0.61Comparison: SAIT101 versus MabThera
SecondaryComplete 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.
Reported as:
Count of participants · Participants
Complete Response (CR) at Weeks 12 and 28
ParticipantsSAIT101MabThera
CR at Week 123937
CR at Week 285150
SecondaryPartial 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.
Reported as:
Count of participants · Participants
Partial Response (PR) at Weeks 12 and 28
ParticipantsSAIT101MabThera
PR at Week 124868
PR at Week 284753
SecondaryStable 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.
Reported as:
Count of participants · Participants
Stable Disease (SD) at Weeks 12 and 28
ParticipantsSAIT101MabThera
SD at Week 125039
SD at Week 282227
SecondaryProgressive 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.
Reported as:
Count of participants · Participants
Progressive Disease (PD) at 12 and 28 Weeks
ParticipantsSAIT101MabThera
PD at Week 1241
PD at Week 282011
SecondaryTime 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
Reported as:
Mean · Weeks
Time to Event (TTE)
WeeksSAIT101MabThera
Time to Event (TTE)23.50 ± 7.50024.08 ± 6.767
Statistical analysis
  • SAIT101 vs MabThera · Hazard ratio (hr): 1.724 · 95% CI 0.853 to 3.482Hazard Ration of TTE SAIT101:MabThera
Other pre-specifiedTruncated 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
Reported as:
Geometric mean · H*µg/ml
Truncated Area Under the Concentration-time Curve (AUC) Over the First and Fourth Dosing Intervals (AUC0 168,w1, AUC0-168,w4).
H*µg/mlSAIT101MabThera
AUC0-168, week 120140 ± 18.719860 ± 18.3
AUC0-168, week 441290 ± 19.042600 ± 19.4
Statistical analysis
  • SAIT101 vs MabThera · Gls mean difference (%): 101.39 · 90% CI 95.86 to 107.24Comparison: SAIT101 versus MabThera. Equivalence was demonstrated for SAIT101 and MabThera with exposure pharmacokinetic parameter AUC0-168,w1 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).
  • SAIT101 vs MabThera · Gls mean difference (%): 96.92 · 90% CI 90.85 to 103.40Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with exposure PK parameter AUC0-168,w4 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).
Other pre-specifiedMaximum 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
Reported as:
Geometric mean · µg/ml
Maximum Concentration (Cmax) After the First Dose and the Fourth Dose (Cmax,w1, Cmax,w4).
µg/mlSAIT101MabThera
Cmax, week 1199.3 ± 22.1200.6 ± 27.5
Cmax, week 4333.6 ± 22.8336.2 ± 20.2
Statistical analysis
  • SAIT101 vs MabThera · Gls mean ratio (%): 99.35 · 90% CI 90.85 to 103.40Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with Cmax,w1 exposure within the standard acceptance limits for bioequivalence (80.00% to 125.00%).
  • SAIT101 vs MabThera · Gls mean ration (%): 99.23 · 90% CI 92.96 to 105.92Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with exposure PK parameter Cmax,w4 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).
Other pre-specifiedAccumulation 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
Reported as:
Geometric mean · Ratio
Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC).
RatioSAIT101MabThera
Accumulation Ratio for AUC0-168 Obtained From the Fourth Dose Versus the First Dose (RAUC).2.075 ± 17.22.137 ± 21.0
Other pre-specifiedAccumulation 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
Reported as:
Geometric mean · Ratio
Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax).
RatioSAIT101MabThera
Accumulation Ratio for the Maximum Plasma Concentration (Cmax) From the Fourth Dose Versus the First Dose (RCmax).1.706 ± 23.21.671 ± 21.0
Other pre-specifiedTrough 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
Reported as:
Geometric mean · µg/ml
Trough Concentrations on Days 1, 8, 15, 22, and 29 (Ctrough).
µg/mlSAIT101MabThera
Ctrough Day 860.60 ± 45.561.00 ± 43.4
Ctrough Day 15108.1 ± 26.0107.3 ± 32.0
Ctrough Day 22143 ± 23.8143.3 ± 30.0
Ctrough Day 29181.7 ± 22.1190.4 ± 26.1
Statistical analysis
  • SAIT101 vs MabThera · Gls mean ratio (%): 95.45 · 90% CI 88.85 to 102.55Comparison: SAIT101 versus MabThera. Pharmacokinetic equivalence was demonstrated for SAIT101 and MabThera with exposure PK parameter Ctrough,d29 within the standard acceptance limits for bioequivalence (80.00% to 125.00%).
Other pre-specifiedObserved 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.
Reported as:
Mean · cells/μL
Observed Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
cells/μLSAIT101MabThera
Week 1 Mean Change from Baseline-128.0 ± 115.71-141.6 ± 120.90
Week 2 Mean Change from Baseline-144.1 ± 123.34-146.8 ± 138.76
Week 3 Mean Change from Baseline-142.8 ± 122.63-157.4 ± 102.03
Week 4 Mean Change from Baseline-141.5 ± 122.92-141.2 ± 102.03
Week 5 Mean Change from Baseline-140.0 ± 120.74-158.5 ± 134.27
Week 12 Mean Change from Baseline-144.2 ± 122.09-160.1 ± 134.09
Week 20 Mean Change from Baseline-140.8 ± 117.98-159.5 ± 135.63
Week 28 Mean Change from Baseline-136.6 ± 122.80-148.2 ± 134.79
Other pre-specifiedPercent 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.
Reported as:
Mean · Percent change
Percent Change From Baseline CD19+ B-Lymphocyte Cluster of Differentiation 19 (CD-19+ B-Cell) Counts up to Week 28
Percent changeSAIT101MabThera
Week 1 % Change from Baseline-89.02 ± 26.324-95.58 ± 8.294
Week 2 % Change from Baseline-100.00 ± 0.000-94.62 ± 1.230
Week 3 % Change from Baseline-100.00 ± 0.000-100.00 ± 0.000
Week 4 % Change from Baseline-100.00 ± 0.000-100.00 ± 0.000
Week 5 % Change from Baseline-100.00 ± 0.000-100.00 ± 0.000
Week 12 % Change from Baseline-100.00 ± 0.000-100.00 ± 0.000
Week 20 % Change from Baseline-100.00 ± 0.000-100.00 ± 0.000
Week 28 % Change from Baseline-97.42 ± 12.749-100.00 ± 0.000
Other pre-specifiedArea 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.
Reported as:
Mean · cells*day/µL)
Area Under the Curve Change From Baseline B-lymphocyte Cluster of Differentiation 19 (CD19+ B-cell) Count Time Curve (AUEC) Over the Dosing Interval
cells*day/µL)SAIT101MabThera
AUEC0-168,w1 (cells*day/µL)-946.0 ± 830.29-1000 ± 891.82
AUEC0-168,w2 (cells*day/µL)-987.2 ± 997.57-1104 ± 947.68
AUEC0-168,w3 (cells*day/µL)-944.8 ± 910.79-1073 ± 930.95
AUEC0-168,w4 (cells*day/µL)-956.3 ± 728.52-1196 ± 1153.7
AUEC0-w12 (cells*day/µL)11330 ± 9854.1-12280 ± 10185
AUEC0-w28 (cells*day/µL)-26370 ± 22794-28860 ± 25439
Other pre-specifiedNormalized 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.
Reported as:
Mean · cells/µL
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
cells/µLSAIT101MabThera
AUEC0-168,w1, normalized (cells/µL)-135.0 ± 118.88-142.1 ± 125.23
AUEC0-168,w2, normalized (cells/µL)-137.1 ± 123.43-155.1 ± 133.38
AUEC0-168,w3, normalized (cells/µL)-134.3 ± 121.75-155.7 ± 135.47
AUEC0-168,w4, normalized (cells/µL)-138.7 ± 121.62-159.2 ± 136.55
AUEC0-w12, normalized (cells/µL)-143.0 ± 121.38-158.7 ± 133.02
Statistical analysis
  • SAIT101 vs MabThera · Mean difference (final values): 7.2 · 90% CI -31.0 to 45.4Comparison: SAIT101 versus MabThera
  • SAIT101 vs MabThera · Mean difference (final values): 18.0 · 90% CI -21.6 to 57.6Comparison: SAIT101 versus MabThera.
  • SAIT101 vs MabThera · Mean difference (final values): 21.4 · 90% CI -18.3 to 61.0Comparison: SAIT101 versus MabThera.
  • SAIT101 vs MabThera · Mean difference (final values): 20.4 · 90% CI -19.3 to 60.2comparison: SAIT101 versus MabThera
  • SAIT101 vs MabThera · Mean difference (final values): 15.7 · 90% CI -23.1 to 54.6Comparison: SAIT101 versus MabThera
  • SAIT101 vs MabThera · Mean difference (final values): 12.8 · 90% CI -26.0 to 51.8Comparison: SAIT101 versus MabThera.
Other pre-specifiedIncidence 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.
Reported as:
Count of participants · Participants
Incidence of Antidrug Antibodies (ADA) and Neutralising Antibody (NAb) by Visit
ParticipantsSAIT101MabThera
Week 1 (Baseline) ADA — Negative138148
Week 1 (Baseline) ADA — Positive32
Week 1 (Baseline) NAb — Negative32
Week 1 (Baseline) NAb — Positive00
Week 2 ADA — Negative143152
Week 2 ADA — Positive10
Week 2 NAb — Negative10
Week 2 NAb — Positive00
Week 3 ADA — Negative138148
Week 3 ADA — Positive52
Week 3 NAb — Negative52
Week 3 NAb — Positive00
Week 4 ADA — Negative145149
Week 4 ADA — Positive20
Week 4 NAb — Negative20
Week 4 NAb — Positive00
Week 5 ADA — Negative139145
Week 5 ADA — Positive20
Week 5 NAb — Negative20
Week 5 NAb — Positive00
Week 12 ADA — Negative137144
Week 12 ADA — Positive30
Week 12 NAb — Negative30
Week 12 NAb — Positive00
Week 20 ADA — Negative131144
Week 20 ADA — Positive74
Week 20 NAb — Negative74
Week 20 NAb — Positive00
Week 28 ADA — Negative126129
Week 28 ADA — Positive1016
Week 29 NAb — Negative916
Week 29 NAb — Positive10
Other pre-specifiedObserved 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.
Reported as:
Mean · Mg/dL
Observed Change From Baseline for Immunoglobulins G and M by Scheduled Time
Mg/dLSAIT101MabThera
IgG Week 2-0.21 ± 132.687-14.79 ± 132.64
IgG Week 3-17.08 ± 157.848-30.04 ± 124.814
IgG Week 4-36.31 ± 132.326-34.64 ± 156.790
IgG Week 5-34.62 ± 162.748-38.21 ± 170.758
IgG Week 12-28.15 ± 159.898-2.30 ± 202.017
IgG Week 20-26.86 ± 189.937-22.40 ± 173.420
IgG Week 28-19.33 ± 200.698.70 ± 238.309
IgM Week 20.34 ± 18.0184.60 ± 28.273
IgM Week 30.87 ± 25.0922.12 ± 32.569
IgM Week 40.64 ± 31.8360.03 ± 30.009
IgM Week 5-1.91 ± 29.521-2.02 ± 21.651
IgM Week 128.02 ± 37.8769.12 ± 21.671
IgM Week 20-12.94 ± 46.966-14.35 ± 26.012
IgM Week 28-22.08 ± 29.200-20.85 ± 37.475
Other pre-specifiedExploratory 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
Reported as:
Count of participants · Participants
Exploratory Analyses of Tumor Response and Time to Event
ParticipantsSAIT101MabThera
Complete Response (CR)5350
Partial Response (PR)4755
Stable Disease (SD)2125
Progressive Disease (PD)1911
Unknown (UKN)12
No Evidence of Disease (NED)41
Other pre-specifiedSubgroups 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
Reported as:
Number · percentage of participants
Subgroups and Treatment Interactions of Overall Response Rate (ORR) by Region, Age, Gender and Anti-Drug Antibody (ADA) Status at Week 28.
percentage of participantsSAIT101MabThera
ORR European Union (%)68.5 (57.96 to 77.77)70.2 (59.90 to 79.21)
ORR Other Region (%)54.8 (41.03 to 66.30)57.8 (44.82 to 70.06)
ORR Age 10-60 years (%)58.6 (47.55 to 69.08)70.6 (59.71 to 99.98)
ORR Age >60 years (%)67.1 (54.88 to 77.91)58.9 (46.77 to 70.29)
ORR Gender Female (%)72.1 (61.38 to 81.23)67.0 (56.21 to 76.70)
ORR Gender Male (%)50.7 (38.56 to 62.78)62.9 (50.48 to 74.11)
ORR ADA Positive (%)42.1 (20.25 to 66.50)57.1 (34.02 to 78.18)
ORR ADA Negative (%)65.4 (56.68 to 73.44)66.7 (58.04 to 74.54)
Statistical analysis
  • SAIT101 vs MabThera · Gail-Simon · p = 0.587 (The p-value was calculated using Gail-Simon Test for Qualitative Interactions.)
  • SAIT101 vs MabThera · Gail-Simon · p = 0.421 (The p-value was calculated using Gail-Simon Test for Qualitative Interactions.)
  • SAIT101 vs MabThera · Gail-Simon · p = 0.288 (The p-value was calculated using Gail-Simon Test for Qualitative Interactions.)
  • SAIT101 vs MabThera · Gail-Wilson · p = 0.588 (The p-value was calculated using Gail-Simon Test for Qualitative Interactions.)

Adverse events

Collected over 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.. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
SAIT1010/157 (0%)3/157 (1.9%)85/157 (54.1%)
MabThera1/158 (0.6%)4/158 (2.5%)70/158 (44.3%)
Most frequent serious events
Most frequent serious events
EventSAIT101MabThera
NeutropeniaBlood and lymphatic system disorders1/1570/158
Cystitis klebsiellaInfections and infestations1/1570/158
ParaesthesiaNervous system disorders1/1570/158
Atrial fibrillationCardiac disorders0/1571/158
Sudden cardiac deathGeneral disorders0/1571/158
Vestibular neuronitisInfections and infestations0/1571/158
FallInjury, poisoning and procedural complications0/1571/158
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders0/1571/158
Most frequent other events
Showing 10 of 16
Most frequent other events
EventSAIT101MabThera
Infusion related reactionInjury, poisoning and procedural complications18/15726/158
HeadacheNervous system disorders9/1572/158
PruritusSkin and subcutaneous tissue disorders4/1578/158
NeutrpopeniaBlood and lymphatic system disorders7/1571/158
FatigueGeneral disorders6/1577/158
NauseaGastrointestinal disorders6/1574/158
DiarrhoeaGastrointestinal disorders5/1575/158
Abdominal pain upperGastrointestinal disorders4/1573/158
AstheniaGeneral disorders4/1574/158
PyrexiaGeneral disorders4/1572/158

Baseline characteristics

Full Analysis Set (FAS)

Age, Continuous
Age, Continuous(years)SAIT101MabTheraTotal
Mean57.8 ± 12.3858.4 ± 12.7858.1 ± 12.57
Sex: Female, Male
Sex: Female, Male(Participants)SAIT101MabTheraTotal
Female8688174
Male7170141
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)SAIT101MabTheraTotal
Hispanic or Latino11718
Not Hispanic or Latino136139275
Unknown or Not Reported101222
Race (NIH/OMB)
Race (NIH/OMB)(Participants)SAIT101MabTheraTotal
American Indian or Alaska Native112
Asian313061
Native Hawaiian or Other Pacific Islander000
Black or African American112
White115111226
More than one race123
Unknown or Not Reported81321
Region of Enrollment
Region of Enrollment(participants)SAIT101MabTheraTotal
Hungary4913
Czechia262450
United States235
United Kingdom314
Spain182240
South Korea101222
Turkey9918
Italy13821
Mexico112
South Africa628
Australia358
Chile213
France7815
Germany549
Ukraine5813
Thailand314
Serbia134
Panama101
India161632
Georgia224
Guatemala235
Belarus10515
Croatia022
Egypt7815
Philippines112
Height (cm)
Height (cm)(cm)SAIT101MabTheraTotal
Mean165.96 ± 9.436165.71 ± 10.650165.84 ± 10.048
Weight at baseline (kg)
Weight at baseline (kg)(kg)SAIT101MabTheraTotal
Mean73.80 ± 15.10773.54 ± 16.60273.67 ± 15.850
Body Mass Index (kg/m^2)
Body Mass Index (kg/m^2)(kg/m^2)SAIT101MabTheraTotal
Mean26.76 ± 4.85726.66 ± 4.96726.71 ± 4.905

8 further baseline measures are reported on the registry.

08

Study locations

25 sites
  • Research site
    Whittier, California 90603, United States
  • Research Site
    Canberra, Australian Capital Territory 2605, Australia
  • Research site
    Temuco, Araucania 4810469, Chile
  • Research site
    Hradec Kralove, 500 05, Czechia
  • Research site
    Praha, 128 08, Czechia
  • Reasearch site
    Praha, 15000, Czechia
  • Research site
    Libourne Cedex, 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
    Busan, 49241, Korea, Republic of
  • Research site
    Seoul, 01757, Korea, Republic of
  • Research site
    Seoul, 03080, Korea, Republic of
  • Research site
    Mexico City, Distrito Federal 03720, Mexico
  • Research site
    Pretoria, Gauteng 0181, South Africa
  • Research site
    L'Hospitalet de Llobregat, Barcelona 08907, Spain
  • Research site
    Cádiz, 11009, Spain
  • Research site
    Madrid, 28040, Spain
  • Research site
    Ankara, 06340, Turkey
  • Research site
    Istanbul, 34098, Turkey
  • Research site
    Mersin, 33343, Turkey
  • Research site
    Samsun, 55139, Turkey
  • Research site
    Norwich, Norfolk NR4 7UY, United Kingdom
09

References and documents

Study documents

  • Study protocol · Nov 3, 2017
  • Statistical analysis plan · Sep 10, 2019

Documents are hosted by the registry — open the source record to download them.

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 8, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02809053
Lead sponsor
Archigen Biotech Limited
Responsible party
Sponsor
First posted
Jun 22, 2016
Start date
Jan 18, 2017
Primary completion
Jul 17, 2019
Completion
Jan 10, 2020
Results posted
Oct 8, 2020
Last update
Oct 8, 2020

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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