E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Participants with AML/secondary AML who are in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (MRD+ post aHSCT) |
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E.1.1.1 | Medical condition in easily understood language |
Participants with AML/secondary AML who are in complete remission with positive measurable residual disease post-allogeneic hematopoietic stem cell transplantation (MRD+ post aHSCT) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
adults only (safety run-in & expansion): to evaluate preliminary efficacy of MBG453 as monotherapy and in combination with aza on prevention of hematologic relapse by assessing proportion of adult participants with AML and MRD+ post aHSCT who remain with no evidence of hematologic relapse after 6 cycles adults only safety run-in: determine if MBG453 as monotherapy at the 2 tested dose levels leads to unacceptable toxicity when administered to adult participants who are in complete remission but are MRD+ post aHSCT adolescents only: to determine if MBG453 as monotherapy at the recommended dose level for adults leads to unacceptable toxicity when administered to adolescent participants who are in complete remission but are MRD+ post aHSCT |
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E.2.2 | Secondary objectives of the trial |
1. to assess the incidence of Grade III or IV aGvHD and moderate to severe cGvHD 2. to characterize PK of MBG453 3. to assess GvHD-free/relapse free survival (GRFS) 4. to assess relapse-free survival (RFS) 5. to determine safety and tolerability of MBG453 in monotherapy and in combination with azacitidine 6. To assess severe immune-related adverse events not attributed to GvHD 7. To assess the proportion of participants with centrally confirmed MRD+ at screening who become MRD- during the first 6 cycles of study treatment |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study. 2. At the date of signing the informed consent form (ICF), eligible participants must be ≥ 18 years for the adult cohorts; and ≥ 12 years old but < 18 years old for the adolescent cohort (cohort 5), which will open after completion of Safety Run-in. 3. Diagnosis of AML/secondary AML and received one prior aHSCT performed to control AML 4. Participants in complete remission (< 5% bone marrow blasts, absence of circulating blasts, and absence of extramedullary disease) with MRD positivity by local assessmentor or by central assessment where required (e.g. USA sites), any time at ≥ Day 60 after aHSCT. 5. Ability to provide a fresh bone marrow aspirate sample collected within 28 days from enrollment/randomization, and immediately shipped to a Novartis designated central laboratory for MRD testing. 6. Systemic GvHD prophylaxis or treatment [immunosuppressive treatment (IST)] completely tapered for at least two weeks prior to study entry. Prednisone dose ≤ 5 mg/day or equivalent corticosteroid dose is allowed. 7. Participants who are found with MRD positivity while still on or tapering systemic GvHD prophylaxis or treatment, MRD positivity must be re-confirmed at least 2 week after the last dose of IST 8. For the adult cohorts, participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. For the adolescent cohort, participants must have a Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance status score ≥ 50%.
Additional inclusion criteria as per full protocol may apply |
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E.4 | Principal exclusion criteria |
1. Prior exposure to TIM-3 directed therapy at anytime 2. History of severe hypersensitivity reactions to any ingredient of study drug(s) (azacitidine, sabatolimab) or monoclonal antibodies (mAbs) and/or their excipients 3. Active Hepatitis B (HBV) or Hepatitis C (HCV) infection. Participants whose disease is controlled under antiviral therapy should not be excluded. 4. Active acute GvHD grade III-IV according to standard criteria (Harris 2016). 5. Active moderate chronic GvHD of the lungs according to NIH consensus criteria. Active severe chronic GvHD according to NIH consensus criteria. 6. History of another primary malignancy that is currently clinically significant or currently requires active intervention. Participants who are receiving adjuvant therapy, such as hormone therapy, are eligible. 7. Any concurrent severe and/or active uncontrolled infection requiring parenteral antibacterial, antiviral or antifungal therapy (such as severe pneumonia, meningitis, or septicemia 8. Active autoimmune disease requiring systemic therapy (e.g. corticosteroids). Topical, inhaled, nasal and ophthalmic steroids are not prohibited. Replacement corticosteroids therapy is allowed and not considered a form of systemic treatment 9. Live vaccine administered within 30 days prior to the first day of study treatment (C1D1) 10. Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) or history of serious organ dysfunction or disease involving the heart, kidney, or liver
Additional exclusion criteria as per full protocol may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. incidence of dose limiting toxicities (safety run-in in adult cohorts 1 and 2 only) 2. percentage of adult subjects with absence of haematologic relapse per investigator assessment (safety run-in and expansion) 3. incidence of dose limiting toxicities (safety confirmation in adolescent cohort 5 only) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. from Cycle 1 Day 1 to end of Cycle 6 (cycle = 28 days) 2. from Cycle 1 Day 1 to end of Cycle 6 (cycle = 28 days) 3. from Cycle 1 Day 1 to end of Cycle 2 (cycle = 28 days)
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E.5.2 | Secondary end point(s) |
1. Incidence of Grade III or IV acute Graft versus Host Disease (aGvHD) 2. incidence of moderate to severe chronic Graft versus Host Disease (cGvHD) 3. Peak of serum concentration (Cmax) sabatolimab 4. Trough serum concentration (Cmin) sabatolimab 5. Anti-drug antibody (ADA) prevalence on-treatment 6. ADA prevalence at baseline 7. time from start of treatment to the date of first documented GvHD-free/relapse-free survival 8. time from start of treatment to the date of first documented haematologic relapse or death due to any cause, whichever occurs first 9. incidence of Grade 3 immune-related adverse events not attributed to GvHD 10. percentage of participants with measurable residual disease (MRD) positive at baseline (BL) who become MRD negative |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. from start of treatment to up to 36 m from LPFT 2. from start of treatment to up to 36 m from LPFT 3. C1 D1 or 5 (end of infusion) and C3 D1 or 5 (EoI) for adult cohorts and C1 D1 (EoI) and C3 D1 (end of infusion) for adolescent cohort (cycle = 28d) 4. D1 or D5 of C1, 3,6 and 24 for adult cohorts and D1 of C1, 2, 3, 6, 9, 12, 18 and 24 for adolescent cohort, and through treatment completion, and average of 15 m 5. through study till 150d safety followup 6. prior to first dose of MBG453 on C1 7. every 2 w until W9, every 4 w until W25, and then every 8 w until end of treatment and then every 12 w for up to 36 m from LPFT 8. every 4 w until W13, then every 12 w till W49, every 24 w after up to 36 m from LPFT 9. through study till 150d safety FU 10. start of treatment to end C6 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
France |
Germany |
Italy |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 20 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 21 |