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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-003669-21 | EudraCT Number |
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Study was stopped following a strategic decision from the Sponsor. It was not based on any safety findings or safety concerns with sabatolimab.
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The purpose of the study was to find out if the new drug sabatolimab when given in combination with azacitidine and venetoclax, was safe and had beneficial effects in participants with high or very high risk myelodysplastic syndrome (MDS) who were not suitable for treatment with intensive chemotherapy or a stem-cell transplant (HSCT).
Approximately 76 people with high or very high risk myelodysplastic syndrome (MDS) and age ≥ 18 years were to be asked to join this study but due to the decision by Novartis to halt recruitment the study did not enroll the approximately 76 participants.
The primary purpose of Part 1 (Safety run-in) was to rule out excessive toxicity of sabatolimab, when administered in combination with azacitidine and venetoclax. The primary purpose of the combined cohort 2 of the Safety run-in (Part 1) and Expansion (Part 2) was to have evaluated efficacy of sabatolimab, when administered in combination with azacitidine and venetoclax in adult participants with high or very high risk MDS. But due to the decision by Novartis to halt recruitment at the end of the Safety run-in, the study enrolled participants in Part 1 only.
This study was to have consisted of two parts:
Safety Run-in Part:
The first approximately 18 participants to have joined the study would have been part of the safety run-in. The first approximately 6 participants would have been enrolled to the lower dose given every four weeks sabatolimab safety run-in cohort.
After these participants would have completed 2 cycles of treatment a decision would have been made to confirm whether the chosen combination of sabatolimab with azacitidine and venetoclax was considered safe to continue with approximately 12 participants, to have been enrolled to the higher dose given every four weeks safety run-in cohort. After these participants would have completed 2 cycles of treatment a decision would have been made to confirm whether the chosen combination of sabatolimab with azacitidine and venetoclax was considered safe to continue with expansion part of the study.
Expansion Part (which did not occur):
After the safety run-in part would have confirmed that the study treatment (higher dose of sabatolimab given every four weeks with azacitidine and venetoclax) was safe, about 58 more participants would have been enrolled in the expansion part to better investigate the efficacy of the study treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| sabatolimab + azacitidine + venetoclax | Experimental | Part 1: Safety run-in consisted of 2 subsequent cohorts of a lower dose (cohort 1) and a higher dose (cohort 2) of sabatolimab in combination with fixed dose of venetoclax and azacitidine. Part 2 (did not start as recruitment was stopped in Part 1) Expansion was to enroll additional participants to further investigate the regimen including sabatolimab at the higher dose, azacitidine and venetoclax. Participants data from Part 1 and Part 2 treated with the higher dose was to have been combined to determine the complete remission rate. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sabatolimab | Drug | Sabatolimab was administered at a low dose (Safety run-in (Part 1) cohort 1) or a high dose (Safety run-in (Part 1) cohort 2) via i.v. infusion over 30 minutes on Day 8 of every treatment cycle. Cycle = 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of Dose Limiting Toxicities (DLTs) - All Grades (Safety run-in Patients Only) | A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor or in combination with other component(s) of study treatment that occurs during the DLT observation period and meets severity criteria as per protocol. | From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days) |
| Percentage of Participants (Receiving 800mg Sabatolimab) Achieving Complete Remission (CR) Per Investigator Assessment | This endpoint assessed Complete Remission (CR) Rate of participants from Cohort 2 of Part 1 and Part 2 according to Investigator assessment per modified IWG-MDS - Cheson 2006 criteria. CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood. | up to approx. 23 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Subjects Achieving a Complete Remission (CR) + Morphologic Complete Remission (mCR): Safety run-in (Part 1) | Assessed the durability of complete remission (CR) or morphologic complete remission (mCR) rate. mCR is defined as <=5% blasts and blast count decrease by >=50% compared to baseline as per modified IWG-MDS Cheson 2006 criteria. | up to approx. 23 months |
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Inclusion Criteria:
Signed informed consent must be obtained prior to participation in the study
Age ≥ 18 years at the date of signing the informed consent form (ICF)
Morphologically confirmed diagnosis of myelodysplastic syndrome (MDS) based on 2016 WHO classification (Arber et al, 2016) by local investigator assessment with one of the following Prognostic Risk Categories, based on the revised International Prognostic Scoring System (IPSS-R) (Greenberg et al 2012):
Not immediately eligible for hematopoietic stem-cell transplantation (HSCT) or intensive chemotherapy at the time of screening due to individual clinical factors such as age, comorbidities and performance status, donor availability (de Witte et al 2017)
Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Brasschaat | 2930 | Belgium | |||
| Novartis Investigative Site |
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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Prior to dosing at Cycle 1 Day 1, participants who fulfilled all the inclusion/exclusion criteria were enrolled via IRT and a treatment number was provided for the study treatments sabatolimab, venetoclax, and azacitidine.
Ten centers across 7 countries enrolled a total of 20 participants in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sabatolimab (MBG453) 400 mg + AZA + VEN (Part 1 Cohort 1) | Part 1 Cohort 1: Safety run-in cohort of a lower dose of sabatolimab in combination with fixed dose of venetoclax and azacitidine. |
| FG001 | Sabatolimab (MBG453) 800 mg + AZA + VEN (Part 1 Cohort 2) |
| 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 | Oct 6, 2021 | Feb 14, 2024 |
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| azacitidine | Drug | A standard dose of azacitidine was given subcutaneously or intravenously every day for seven consecutive days on days 1-7 of a confirmed treatment cycle. In keeping with standard clinical practice, the alternative schedules for five consecutive days on days 1-5, followed by a two day break, then two consecutive days on days 8-9 was permitted (alternative schedule). |
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| venetoclax | Drug | Venetoclax film-coated tablets was administered at a dose of 400 mg orally or corresponding reduced dose for concomitant use with P-gp inhibitors or moderate or strong CYP3A4 inhibitors, once a day, from C1D1 to C1D14 during the treatment cycle. No ramp-up for venetoclax was necessary. |
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| Overall Response Rate (ORR) of Participants Who Achieved Hematologic Improvement (HI) or Better as Best Response | The percentage of participants achieving [CR + mCR + partial remission (PR) + hematologic improvement (HI)], per modified IWG-MDS Cheson 2006 criteria. Partial response (PR): all complete response (CR) criteria except >=50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow >5%. HI (erythroid response or platelet response or neutrophil response) must last at least 8 weeks. | up to approx. 23 months |
| Percentage of Participants Who Are RBC/Platelets Transfusion Independent | Improvement in red blood cells (RBC)/platelets transfusion post-baseline as per International Working Group - Myelodysplastic syndromes (IWG-MDS) by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)) and for participants treated with sabatolimab 800 mg (Q4W) (Cohort 2 of safety run-in and expansion parts). RBC/Platelets transfusion independence is defined as participants having received no RBC/Platelets transfusions during at least 8 consecutive weeks after start of treatment. | up to approx. 23 months |
| Duration of Transfusion Independence | Sum of each period of the transfusion independence for participants with at least one period of transfusion independence post-baseline by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)) and for participants treated with sabatolimab 800 mg (Q4W) (Cohort 2 of safety run-in and expansion parts) for both red blood cells and platelets. RBC/Platelets transfusion independence is defined as participants having received no RBC/platelets transfusions during at least 8 consecutive weeks after start of treatment. | up to approx. 23 months |
| Peak Serum Concentration (Cmax) of Sabatolimab | Maximal concentration of sabatolimab for participants treated with sabatolimab by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)). | Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months |
| Trough Serum Concentration (Cmin) Sabatolimab | Concentration of sabatolimab prior to next dosing or after end of treatment by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)). | Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months |
| Anti-drug Antibody (ADA) Prevalence at Baseline and ADA Incidence On-treatment by Dose Level | Immunogenicity of sabatolimab prior to sabatolimab exposure and during treatment | Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months |
| Duration of Complete Remission (CR) | Duration of complete remission (CR) is defined as time from first occurrence of CR to relapse from CR, progression or death due to any cause whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood. Relapse from complete remission (CR)is when at least 1 of the following criteria is met:
| up to approx. 23 months |
| Time to Complete Remission(CR)/Marrow Complete Remission (mCR) | Time to CR/mCR is defined as time from start of treatment to first occurrence of CR or mCR as per investigator assessment for the safety run-in part (Cohort 2 (800 mg Q4W)). | up to approx. 23 months |
| Duration of Complete Response (CR)/Marrow Complete Response (mCR) | Duration of CR/mCR is defined as time from first occurrence of CR/mCR to relapse from CR, progression or death due to any cause whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). | up to approx. 23 months |
| Duration of Response for Participants Who Achieved Hematologic Improvement (HI) or Better | The duration of response was derived for participants treated with sabatolimab at the higher dose who achieved HI or better as per investigator assessment and is defined from the first occurrence of complete response (CR), marrow complete response (mCR), partial response (PR) or hematologic improvement (HI) until relapse, progression or death due to any reason for the safety run-in part (Cohort 2 (800 mg Q4W)). | up to approx. 23 months |
| Progression-Free Survival (PFS) | Time from start of treatment to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). | up to approx. 23 months |
| Leukemia-Free Survival (LFS) | Time from start of treatment to transformation to acute leukemias per investigator assessment [as defined as ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification) or diagnosis of extramedullary acute leukemia or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)).](streamdown:incomplete-link) | up to approx. 23 months |
| Event-Free Survival (EFS) | Time from start of treatment to lack of reaching CR within the first 6 cycles, relapse from CR or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). | up to approx. 23 months |
| Overall Survival (OS) | Time from start of treatment to death due to any cause for the safety run-in part (Cohort 2 (800 mg Q4W)). | Date of start of treatment to date of death due to any reason, for up to approx. 23 months |
| Changes in Fatigue (Part 2 - Expansion) | Changes in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue for participants treated with sabatolimab at the higher dose of the expansion part only. Measurements would have been taken via scores from 0 (not at all) to 4 (very much). The higher the score, the better the Quality of Life. | throughout study until progressive disease, death or study discontinuation, approx. 3 years |
| Marseille |
| 13273 |
| France |
| Novartis Investigative Site | Nice | 06202 | France |
| Novartis Investigative Site | Düsseldorf | 40479 | Germany |
| Novartis Investigative Site | Stuttgart | 70376 | Germany |
| Novartis Investigative Site | Alexandroupoli | Evros | 681 00 | Greece |
| Novartis Investigative Site | Pátrai | 265 00 | Greece |
| Novartis Investigative Site | Nyíregyháza | 4400 | Hungary |
| Novartis Investigative Site | Genova | GE | 16132 | Italy |
| Novartis Investigative Site | Barcelona | Catalonia | 08036 | Spain |
Part 1 Cohort 2: Safety run-in cohort of a higher dose of sabatolimab in combination with fixed dose of venetoclax and azacitidine. |
| Did Not Enter Post-treatment Follow-up |
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| Entered Post-treatment Follow-up |
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| COMPLETED | Completed = completed treatment Not completed = discontinued from treatment |
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| NOT COMPLETED |
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Full Analysis Set (FAS):
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| ID | Title | Description |
|---|---|---|
| BG000 | Sabatolimab (MBG453) 400 mg + AZA + VEN (Part 1 Cohort 1) | Part 1 Cohort 1: Safety run-in cohort of a lower dose of sabatolimab in combination with fixed dose of venetoclax and azacitidine. |
| BG001 | Sabatolimab (MBG453) 800 mg + AZA + VEN (Part 1 Cohort 2) | Part 1 Cohort 2: Safety run-in cohort of a higher dose of sabatolimab in combination with fixed dose of venetoclax and azacitidine. |
| 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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| Race/Ethnicity, Customized | 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 | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Rate of Dose Limiting Toxicities (DLTs) - All Grades (Safety run-in Patients Only) | A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value considered by the Investigator to be at least possibly related to sabatolimab as a single contributor or in combination with other component(s) of study treatment that occurs during the DLT observation period and meets severity criteria as per protocol. | Dose determining set (DDS): The DDS included all participants from the FAS enrolled in the Safety run-in part who met the minimum exposure criterion and had sufficient safety evaluations or experienced a dose limiting toxicity (DLT) during the first two cycles. | Posted | Count of Participants | Participants | From Cycle 1 Day 8 to end of Cycle 2 (Cycle = 28 Days) |
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| Primary | Percentage of Participants (Receiving 800mg Sabatolimab) Achieving Complete Remission (CR) Per Investigator Assessment | This endpoint assessed Complete Remission (CR) Rate of participants from Cohort 2 of Part 1 and Part 2 according to Investigator assessment per modified IWG-MDS - Cheson 2006 criteria. CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood. | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. If a participant were assigned to a specific cohort without any administration of sabatolimab, but received venetoclax or azacitidine, the participant is included in the analysis. | Posted | Count of Participants | Participants | up to approx. 23 months |
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| Secondary | Percentage of Subjects Achieving a Complete Remission (CR) + Morphologic Complete Remission (mCR): Safety run-in (Part 1) | Assessed the durability of complete remission (CR) or morphologic complete remission (mCR) rate. mCR is defined as <=5% blasts and blast count decrease by >=50% compared to baseline as per modified IWG-MDS Cheson 2006 criteria. | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. If a participant were assigned to a specific cohort without any administration of sabatolimab, but received venetoclax or azacitidine, the participant is included in the analysis. | Posted | Count of Participants | Participants | up to approx. 23 months |
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| Secondary | Overall Response Rate (ORR) of Participants Who Achieved Hematologic Improvement (HI) or Better as Best Response | The percentage of participants achieving [CR + mCR + partial remission (PR) + hematologic improvement (HI)], per modified IWG-MDS Cheson 2006 criteria. Partial response (PR): all complete response (CR) criteria except >=50% decrease from baseline in blasts in bone marrow AND blast count in bone marrow >5%. HI (erythroid response or platelet response or neutrophil response) must last at least 8 weeks. | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. If a participant were assigned to a specific cohort without any administration of sabatolimab, but received venetoclax or azacitidine, the participant is included in the analysis. | Posted | Count of Participants | Participants | up to approx. 23 months |
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| Secondary | Percentage of Participants Who Are RBC/Platelets Transfusion Independent | Improvement in red blood cells (RBC)/platelets transfusion post-baseline as per International Working Group - Myelodysplastic syndromes (IWG-MDS) by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)) and for participants treated with sabatolimab 800 mg (Q4W) (Cohort 2 of safety run-in and expansion parts). RBC/Platelets transfusion independence is defined as participants having received no RBC/Platelets transfusions during at least 8 consecutive weeks after start of treatment. | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. If a participant were assigned to a specific cohort without any administration of sabatolimab, but received venetoclax or azacitidine, the participant is included in the analysis. | Posted | Count of Participants | Participants | up to approx. 23 months |
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| Secondary | Duration of Transfusion Independence | Sum of each period of the transfusion independence for participants with at least one period of transfusion independence post-baseline by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)) and for participants treated with sabatolimab 800 mg (Q4W) (Cohort 2 of safety run-in and expansion parts) for both red blood cells and platelets. RBC/Platelets transfusion independence is defined as participants having received no RBC/platelets transfusions during at least 8 consecutive weeks after start of treatment. | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. If a participant were assigned to a specific cohort without any administration of sabatolimab, but received venetoclax or azacitidine, the participant is included in the analysis. Analysis is based on participants with at least one period of transfusion independence post-baseline. | Posted | Mean | Standard Deviation | Weeks | up to approx. 23 months |
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| Secondary | Peak Serum Concentration (Cmax) of Sabatolimab | Maximal concentration of sabatolimab for participants treated with sabatolimab by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)). | PK analysis set: The sabatolimab and venetoclax pharmacokinetic analysis sets included all participants from the Safety Set who provided at least one evaluable sabatolimab/venetoclax PK concentration. No data is reported as only pre-dose samples were collected | Posted | Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months |
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| Secondary | Trough Serum Concentration (Cmin) Sabatolimab | Concentration of sabatolimab prior to next dosing or after end of treatment by dose level for the safety run-in part (Cohort 1 (400 mg Q4W) and Cohort 2 (800 mg Q4W)). | PK analysis set: The sabatolimab pharmacokinetic analysis set included all participants from the Safety Set who provided at least one evaluable sabatolimab PK concentration. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug/ml | Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months |
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| Secondary | Anti-drug Antibody (ADA) Prevalence at Baseline and ADA Incidence On-treatment by Dose Level | Immunogenicity of sabatolimab prior to sabatolimab exposure and during treatment | Immunogenicity (IG) analysis set: included all participants in the Full Analysis Set with a non-missing baseline IG sample or at least one non-missing post-baseline IG sample. A non-missing IG sample was a sample that was analyzed and not ADA-inconclusive. | Posted | Number | Participants | Continuously collected for patients during treatment with sabatolimab up to 150 days after last treatment, approx. 23 months |
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| Secondary | Duration of Complete Remission (CR) | Duration of complete remission (CR) is defined as time from first occurrence of CR to relapse from CR, progression or death due to any cause whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). CR is defined as follows: bone marrow blasts <=5%, hemoglobin level ≥ 10 g/dL, platelets count ≥ 100*10^9/L, neutrophils count ≥ 1.0*10^9/L, absence of blasts in peripheral blood. Relapse from complete remission (CR)is when at least 1 of the following criteria is met:
| Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. Analysis is based on participants with CR. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Time to Complete Remission(CR)/Marrow Complete Remission (mCR) | Time to CR/mCR is defined as time from start of treatment to first occurrence of CR or mCR as per investigator assessment for the safety run-in part (Cohort 2 (800 mg Q4W)). | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Duration of Complete Response (CR)/Marrow Complete Response (mCR) | Duration of CR/mCR is defined as time from first occurrence of CR/mCR to relapse from CR, progression or death due to any cause whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. Analysis is based on participants with CR or mCR. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Duration of Response for Participants Who Achieved Hematologic Improvement (HI) or Better | The duration of response was derived for participants treated with sabatolimab at the higher dose who achieved HI or better as per investigator assessment and is defined from the first occurrence of complete response (CR), marrow complete response (mCR), partial response (PR) or hematologic improvement (HI) until relapse, progression or death due to any reason for the safety run-in part (Cohort 2 (800 mg Q4W)). | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. Analysis is based on participants with CR, mCR, PR or HI. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Progression-Free Survival (PFS) | Time from start of treatment to disease progression (including transformation to acute leukemia per WHO 2016 classification), relapse from CR or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Leukemia-Free Survival (LFS) | Time from start of treatment to transformation to acute leukemias per investigator assessment [as defined as ≥ 20% blasts in bone marrow/ peripheral blood (per WHO 2016 classification) or diagnosis of extramedullary acute leukemia or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)).](streamdown:incomplete-link) | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Event-Free Survival (EFS) | Time from start of treatment to lack of reaching CR within the first 6 cycles, relapse from CR or death due to any cause, whichever occurs first for the safety run-in part (Cohort 2 (800 mg Q4W)). | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | months | up to approx. 23 months |
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| Secondary | Overall Survival (OS) | Time from start of treatment to death due to any cause for the safety run-in part (Cohort 2 (800 mg Q4W)). | Full Analysis Set (FAS): The Full Analysis Set (FAS) comprises all participants who received at least one dose of study treatment. | Posted | Median | 95% Confidence Interval | months | Date of start of treatment to date of death due to any reason, for up to approx. 23 months |
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| Secondary | Changes in Fatigue (Part 2 - Expansion) | Changes in fatigue as measured by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue for participants treated with sabatolimab at the higher dose of the expansion part only. Measurements would have been taken via scores from 0 (not at all) to 4 (very much). The higher the score, the better the Quality of Life. | As expansion phase was not opened, there is no data as nothing was analyzed. | Posted | throughout study until progressive disease, death or study discontinuation, approx. 3 years |
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| Post-Hoc | All Collected Deaths | On-treatment deaths were collected from start of study treatment (FPFT) up to 30 days after study drug discontinuation, for a maximum duration of approx. 23 months. Post-treatment survival follow-up deaths were collected from Day 31 after last dose of study treatment to end of study up to approx. 18 months All deaths refer to the sum of on-treatment and post-treatment survival follow-up deaths, up to approx. 23 months | All enrolled patients | Posted | Count of Participants | Participants | On-treatment deaths: up to approx. 23 months, post-treatment deaths: up to approx 18 months |
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Adverse events were collected from first dose of study treatment to 150 days after last dose of study medication (on-treatment), for sabatolimab and 30 days for azactidine & venetoclax up to approx. 23 months. Deaths were collected in the post treatment survival follow up from 31 days after last dose of study medication until the end of the study, up to approx. 18 months. These are not considered AEs
Any sign or symptom that occurs during the conduct of the trial and safety follow-up. Deaths in the post treatment survival follow-up are not considered Adverse Events. The total number at risk in the post treatment survival includes patients that entered the post treatment survival follow-up period.
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 | Sabatolimab (MBG453) 400 mg + AZA + VEN (Part 1 Cohort 1) - On-treatment | Adverse Events (AEs) during on-treatment period (up to 30 days post-treatment) | 0 | 5 | 3 | 5 | 5 | 5 |
| EG001 | Sabatolimab (MBG453) 800 mg + AZA + VEN (Part 1 Cohort 2) - On-treatment | Adverse Events (AEs) during on-treatment period (up to 30 days post-treatment) | 1 | 15 | 14 | 15 | 15 | 15 |
| EG002 | Sabatolimab (MBG453) 400 mg + AZA + VEN (Part 1 Cohort 1) - Post-treatment Survival Follow-up | Deaths collected in the post- treatment survival follow-up phase (starting from day 31 post- treatment). No AEs were collected during this period | 1 | 5 | 0 | 0 | 0 | 0 |
| EG003 | Sabatolimab (MBG453) 800 mg + AZA + VEN (Part 1 Cohort 2) - Post-treatment Survival Follow-up | Deaths collected in the post- treatment survival follow-up phase (starting from day 31 post- treatment). No AEs were collected during this period | 5 | 14 | 0 | 0 | 0 | 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Febrile bone marrow aplasia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Large intestine perforation | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Autoinflammatory disease | Immune system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Bacterial sepsis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Peritonitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Wound haemorrhage | Injury, poisoning and procedural complications | MedDRA (26.0) | Systematic Assessment |
| |
| Medical observation | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Lung adenocarcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Systematic Assessment |
| |
| Paraneoplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (26.0) | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Bone marrow failure | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haemolysis | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pancytopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Eructation | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Catheter site inflammation | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Device related thrombosis | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Infusion site haematoma | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Injection site erythema | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cholestasis | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hepatic cytolysis | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hepatotoxicity | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypertransaminasaemia | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Jaundice | Hepatobiliary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| COVID-19 | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Clostridium bacteraemia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Escherichia bacteraemia | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Vascular device infection | Infections and infestations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood folate decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| C-reactive protein increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Serum ferritin decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Troponin T increased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (26.0) | Systematic Assessment |
| |
| Cell death | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypernatraemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Malnutrition | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Vitamin K deficiency | Metabolism and nutrition disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haemorrhage intracranial | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cervical polyp | Reproductive system and breast disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Heavy menstrual bleeding | Reproductive system and breast disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Uterine haemorrhage | Reproductive system and breast disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Dermatitis allergic | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Purpura | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
| |
| Thrombosis | Vascular disorders | MedDRA (26.0) | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e., data from all sites) in clinical trial or disclosure of trial results in their entirety.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Disclosure Office | Novartis Pharmaceuticals | 862-778-3000 | novartis.email@novartis.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 6, 2023 | Feb 14, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000723550 | sabatolimab |
| D001374 | Azacitidine |
| C579720 | venetoclax |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
Not provided
Not provided
| Male |
|
| Unknown |
|
| Nervous system disorders (Haemorrhage intracranial) |
|
|
| Participants |
|
|
| Units | Counts |
|---|---|
| Participants |
|
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| Participants |
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