Clinical Trials List
Protocol NumberZB012-03-002
NCT Number(ClinicalTrials.gov Identfier)NCT05786573
Completed
2023-12-01 - 2024-12-04
Phase III
Recruiting4
Terminated1
ICD-10D59.0
Drug-induced autoimmune hemolytic anemia
ICD-10D59.1
Other autoimmune hemolytic anemias
ICD-9283.0
Autoimmune hemolytic anemias
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study, with a Safety and Dose Confirmation Run-in Period, to Evaluate the Efficacy and Safety of Obexelimab in Patients with Warm Autoimmune Hemolytic Anemia (SApHiAre)
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Chien-Chin Lin Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
- Wen-Chien Chou Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 黃文聰 Division of Hematology & Oncology
- 林建良 Division of Hematology & Oncology
- 陳冠宇 Division of Hematology & Oncology
- 高婉真 無
- Shang-Wen Chen Division of Hematology & Oncology
- 曹朝榮 Division of Hematology & Oncology
- 陳昭勳 Division of Hematology & Oncology
- 陳彥勳 Division of Hematology & Oncology
- 林正耀 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Sin-Syue Li Division of General Internal Medicine
- Ya-Ping Chen Division of Hematology & Oncology
- Tsai-Yun Chen Division of Hematology & Oncology
- 傅蓓安 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 高婉真 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
autoimmune hemolytic anemia, AIHA
Objectives
Part A: Safety and Dosage Confirmation Lead-in Period (SRP)
Main security
● To assess the safety and tolerability of weekly subcutaneous (SC) administration of obexelimab in patients with wAIHA
Main therapeutic effect
● To evaluate the clinical benefit of weekly SC administration of obexelimab for anemia in patients with wAIHA
secondary
● To evaluate the clinical benefit of weekly SC administration of obexelimab on additional assessment of disease activity in patients with wAIHA
Part B: Randomized Control Period (RCP)
main
● To evaluate the clinical benefit of weekly SC administration of obexelimab for anemia in patients with wAIHA
secondary
● To evaluate the clinical benefit of weekly SC administration of obexelimab on additional assessment of disease activity in patients with wAIHA
● To assess the safety and tolerability of weekly SC administration of obexelimab in patients with wAIHA
exploratory
● To assess the impact of weekly SC administration of obexelimab on selected quality-of-life assessments
● Evaluate the pharmacokinetic (PK) properties of weekly SC administration of obexelimab in patients with wAIHA
● Assess the immunogenicity of weekly SC administration of obexelimab in patients with wAIHA
● Describe the pharmacodynamic (PD) response to weekly SC administration of obexelimab in patients with wAIHA
Part C: Open Extension (OLE) Period
Main security
● To assess the safety and tolerability of weekly SC administration of obexelimab in patients with wAIHA
Main therapeutic effect
● To assess the Hgb response and overall duration of response to weekly SC administration of obexelimab in patients with wAIHA
● Evaluate the clinical benefit of weekly SC administration of obexelimab as rescue therapy in patients with wAIHA
Test Drug
OBEXELIMAB (XmabR5871)
Active Ingredient
OBEXELIMAB
Dosage Form
Solution of injection
Dosage
125 mg/ml
Endpoints
Part A
-Incidence of adverse events (AEs), serious adverse events (SAEs), and any adverse events of special interest (AESI), as defined by Common Adverse Event Evaluation Criteria version 5.0 (CTCAE v5.0)
-Proportion of patients with hemoglobin (Hgb) ? 10 g/dL at or after week 8 and an increase of ? 2 g/dL since baseline and who did not receive transfusions or glucocorticoid (GC) rescue therapy before achieving response
Part B
-As early as Week 12 or later, after achieving a durable Hgb response (defined as Hgb ? 10 g/dL with at least 3 of 4 consecutive visits increasing ? 2 g/dL since base), and until Week 24 Proportion of patients who had a durable response who had not received prior transfusion or GC rescue therapy
Part C
- Incidence of AEs, SAEs, and any AESI, as defined by CTCAE v5.0
- Proportion of patients with Hgb ? 10 g/dL and an increase of ? 2 g/dL since baseline, and who did not receive transfusions or GC rescue therapy
-Hgb response time in patients achieving durable Hgb response
- Cumulative dose of GC rescue therapy
-Incidence of adverse events (AEs), serious adverse events (SAEs), and any adverse events of special interest (AESI), as defined by Common Adverse Event Evaluation Criteria version 5.0 (CTCAE v5.0)
-Proportion of patients with hemoglobin (Hgb) ? 10 g/dL at or after week 8 and an increase of ? 2 g/dL since baseline and who did not receive transfusions or glucocorticoid (GC) rescue therapy before achieving response
Part B
-As early as Week 12 or later, after achieving a durable Hgb response (defined as Hgb ? 10 g/dL with at least 3 of 4 consecutive visits increasing ? 2 g/dL since base), and until Week 24 Proportion of patients who had a durable response who had not received prior transfusion or GC rescue therapy
Part C
- Incidence of AEs, SAEs, and any AESI, as defined by CTCAE v5.0
- Proportion of patients with Hgb ? 10 g/dL and an increase of ? 2 g/dL since baseline, and who did not receive transfusions or GC rescue therapy
-Hgb response time in patients achieving durable Hgb response
- Cumulative dose of GC rescue therapy
Inclution Criteria
Parts A and B: Inclusion criteria
Patients are eligible for inclusion in an SRP or RCP only if they meet all of the following criteria:
1. Male or female aged ? 18 when signing the subject consent form
2. Have been diagnosed with wAIHA for at least 3 months and are currently receiving wAIHA treatment, or have previously been treated with wAIHA (untreated patients are not eligible)
3. Diagnosis of primary or secondary wAIHA based on positive specific direct antiglobulin test for anti-IgG or anti-IgA
4. Have received at least one failed wAIHA treatment course, including steroids, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, vincristine alkaloids, and erythropoiesis stimulating agents or splenectomy (folic acid, iron, or other supplements do not qualify)
5. If receiving prednisone/adrenocorticosterone, the dose must not exceed 20 mg daily and must have been stable for at least 4 weeks prior to randomization and remain stable throughout SRP and RCP
6. If receiving immunosuppressants, they must have been on a stable dose for at least 12 weeks before randomization and maintained on a stable dose throughout the SRP and RCP periods. Concurrent immunosuppressants are azathioprine, mycophenolate mofetil/mycophenolic acid, cyclosporine, and cyclophosphamide
7. Hgb ? 7 and < 10 g/dL
8. At least one sign or symptom of anemia as assessed by the trial sponsor at screening
9. Screening platelet count ? 50,000 mm3
10. Screening Neutrophil Count ? 1,000 mm3
11. Screen for serum albumin and serum calcium concentrations to be within the normal range
12. Screen for total serum IgG ? 600 mg/dL
13. Screen for creatine stimulation value < 2 × ULN
14. Patients with a history of splenectomy must be at least 4 months post-splenectomy before randomization and must be vaccinated according to the country-specific immunization schedule
15. Patients with autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis) who are receiving stable treatment (no change in disease-related concomitant medications) and whose disease severity has been stable for at least 4 days before randomization months, you may be eligible
16. For SRP (Part A) only, patients with LPD (Group 2) are receiving stable treatment (no change in concomitant disease-related medications), disease severity has been stable for at least 4 months before randomization, and in the opinion of the trial moderator They are unlikely to require chemotherapy or mAb therapy during the trial and may be eligible
17. Women who are not pregnant (please refer to Appendix 4), not breastfeeding, and meet at least one of the following conditions:
a. Females not of childbearing potential (FOCBP) as defined in Annex 4
or
b. FOCBP who have a negative serum pregnancy test result at screening and a negative urine pregnancy test result before the first dose of test drug, and who agree to be pregnant during the trial and at least 1 month after the last dose of test drug (ie: approximately 5 Follow the birth control guidance in Annex 4 for half-life
18. Males who meet the following conditions:
a. Agree to (i) abstain from sexual intercourse during the trial and for at least 1 month (ie: approximately 5 half-lives) after the last dose of IMP, or (ii) use birth control (as described in Attachment 4), or (iii ) was surgically sterilized during the trial
and
b. Agree to avoid sperm donation during the trial and for at least 1 month after the last dose of IMP (ie: approximately 5 half-lives)
19. Ability to provide signed subject consent, including compliance with the requirements and restrictions listed in the ICF and this trial plan
Part C: OLE Period Inclusion Conditions
Patients are eligible for inclusion in the OLE phase if all of the following criteria are met:
1. Complete Week 24 SRP/RCP visit
2. The IMP has not been terminated for any of the following security reasons:
a. Pregnancy
b. Malignant tumors
c. Allergy to IMP
d. Determination of patient ineligibility for RCP
e. Any reason the trial manager deems necessary based on patient safety
3. IMP has not been discontinued due to patient unblinding
4. FOCBP must have a negative serum pregnancy test before inclusion in the OLE period
5. Have not received a blood transfusion within 2 weeks before the first dose of the OLE period
6. Not receiving more than two concomitant medications for the treatment of wAIHA, excluding vitamins or other supplements, at the time of inclusion in the OLE period
7. Patients must receive the first dose of obexelimab during OLE within 14 days of the Week 24 SRP/RCP visit
8. Willing to comply with all trial plan procedures and complete all trial follow-up visits
Patients are eligible for inclusion in an SRP or RCP only if they meet all of the following criteria:
1. Male or female aged ? 18 when signing the subject consent form
2. Have been diagnosed with wAIHA for at least 3 months and are currently receiving wAIHA treatment, or have previously been treated with wAIHA (untreated patients are not eligible)
3. Diagnosis of primary or secondary wAIHA based on positive specific direct antiglobulin test for anti-IgG or anti-IgA
4. Have received at least one failed wAIHA treatment course, including steroids, azathioprine, cyclophosphamide, cyclosporine, mycophenolate mofetil, danazol, vincristine alkaloids, and erythropoiesis stimulating agents or splenectomy (folic acid, iron, or other supplements do not qualify)
5. If receiving prednisone/adrenocorticosterone, the dose must not exceed 20 mg daily and must have been stable for at least 4 weeks prior to randomization and remain stable throughout SRP and RCP
6. If receiving immunosuppressants, they must have been on a stable dose for at least 12 weeks before randomization and maintained on a stable dose throughout the SRP and RCP periods. Concurrent immunosuppressants are azathioprine, mycophenolate mofetil/mycophenolic acid, cyclosporine, and cyclophosphamide
7. Hgb ? 7 and < 10 g/dL
8. At least one sign or symptom of anemia as assessed by the trial sponsor at screening
9. Screening platelet count ? 50,000 mm3
10. Screening Neutrophil Count ? 1,000 mm3
11. Screen for serum albumin and serum calcium concentrations to be within the normal range
12. Screen for total serum IgG ? 600 mg/dL
13. Screen for creatine stimulation value < 2 × ULN
14. Patients with a history of splenectomy must be at least 4 months post-splenectomy before randomization and must be vaccinated according to the country-specific immunization schedule
15. Patients with autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis) who are receiving stable treatment (no change in disease-related concomitant medications) and whose disease severity has been stable for at least 4 days before randomization months, you may be eligible
16. For SRP (Part A) only, patients with LPD (Group 2) are receiving stable treatment (no change in concomitant disease-related medications), disease severity has been stable for at least 4 months before randomization, and in the opinion of the trial moderator They are unlikely to require chemotherapy or mAb therapy during the trial and may be eligible
17. Women who are not pregnant (please refer to Appendix 4), not breastfeeding, and meet at least one of the following conditions:
a. Females not of childbearing potential (FOCBP) as defined in Annex 4
or
b. FOCBP who have a negative serum pregnancy test result at screening and a negative urine pregnancy test result before the first dose of test drug, and who agree to be pregnant during the trial and at least 1 month after the last dose of test drug (ie: approximately 5 Follow the birth control guidance in Annex 4 for half-life
18. Males who meet the following conditions:
a. Agree to (i) abstain from sexual intercourse during the trial and for at least 1 month (ie: approximately 5 half-lives) after the last dose of IMP, or (ii) use birth control (as described in Attachment 4), or (iii ) was surgically sterilized during the trial
and
b. Agree to avoid sperm donation during the trial and for at least 1 month after the last dose of IMP (ie: approximately 5 half-lives)
19. Ability to provide signed subject consent, including compliance with the requirements and restrictions listed in the ICF and this trial plan
Part C: OLE Period Inclusion Conditions
Patients are eligible for inclusion in the OLE phase if all of the following criteria are met:
1. Complete Week 24 SRP/RCP visit
2. The IMP has not been terminated for any of the following security reasons:
a. Pregnancy
b. Malignant tumors
c. Allergy to IMP
d. Determination of patient ineligibility for RCP
e. Any reason the trial manager deems necessary based on patient safety
3. IMP has not been discontinued due to patient unblinding
4. FOCBP must have a negative serum pregnancy test before inclusion in the OLE period
5. Have not received a blood transfusion within 2 weeks before the first dose of the OLE period
6. Not receiving more than two concomitant medications for the treatment of wAIHA, excluding vitamins or other supplements, at the time of inclusion in the OLE period
7. Patients must receive the first dose of obexelimab during OLE within 14 days of the Week 24 SRP/RCP visit
8. Willing to comply with all trial plan procedures and complete all trial follow-up visits
Exclusion Criteria
Patients may not participate in the trial if any of the following conditions are met:
1. Have cold antibody AIHA, cold agglutinin syndrome, mixed (i.e., warm-cold) AIHA, or paroxysmal cold hemoglobinuria
Any other relevant cause of hereditary or acquired hemolytic anemia
3. Applicable to RCP (Part B) only, patients with secondary wAIHA not caused by autoimmune disease (including LPD)
4. Received blood transfusion within 2 weeks before random assignment
5. Use of B-cell depletion, B-cell targeting, or other biological immunomodulators within 6 months prior to randomization. Patients who have received B-cell-targeted therapy within 6 to 12 months prior to randomization must have a B-cell count measured by a central laboratory at screening that falls within the laboratory reference range
6. Received intravenous (IV) Ig or epoetin alfa within 6 weeks before randomization. Patients can be rescreened after the 6-week exclusion period
7. Receiving more than two concomitant medications used to treat wAIHA at the time of screening, excluding vitamins or other supplements
8. Received experimental treatment or direct medical intervention in another clinical trial within 12 weeks before screening or <5 half-lives of the experimental treatment, whichever is shorter
9. Received live vaccine or active therapeutic infectious agent within 6 weeks before randomization
10. Evidence of open tuberculosis (TB) or being at high risk for TB based on at least one of the following:
a. History of open TB or latent TB unless there is a record of completion of treatment according to local guidelines
b. The interferon-γ release assay result during screening is judged to be positive, uncertain or invalid, unless there is a treatment record. Patients with inconclusive test results can be tested again centrally or locally, but if repeated testing is still inconclusive, the patient will be excluded
c. Symptoms and signs that may represent open TB
d. Possible diagnosis of TB on chest radiography, computed tomography, or magnetic resonance imaging
11. Have a history or evidence of a clinically unstable/poorly controlled disorder, condition or disease (including but not limited to cardiopulmonary, oncological, renal, liver, metabolic, hematological, psychiatric, open infection) that the trial moderator believes will be safe for the patient pose a risk, or interfere with trial evaluation, procedures or completion
12. Known hypersensitivity to mAb therapy
13. Known allergy to dextran or dextran components
14. Have an open infection requiring parenteral or oral anti-infective drugs and/or hospitalization (e.g. pneumonia, biliary tract infection, diverticulitis, Clostridium difficile infection) within 8 weeks before screening, and/or have been diagnosed by the trial Moderator assessed as severe/clinically significant. Patients may be rescreened after the 8-week exclusion period.
15. Chronic infection (for example: bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or the need for long-term anti-infective treatment (for example: antibiotics, antiviral drugs)
16. Confirmed or suspected clinical immunodeficiency syndrome unrelated to wAIHA treatment, or a family history of congenital or hereditary immunodeficiency, unless it is confirmed that the patient does not suffer from the above-mentioned diseases
17. Acute hepatitis B infection (positive hepatitis B surface antigen), active hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. Patients will be excluded from the trial if there is a positive test result for active hepatitis B by detection of hepatitis B surface antigen. In Japan, patients were excluded if (a) hepatitis B surface antigen or (b) hepatitis B surface antibody or (c) hepatitis B core antibody was detected. Patients with a history of HCV will be excluded from the trial unless there is data showing negative serum HCV ribonucleic acid concentrations 12 weeks or more after completion of HCV therapy
18. Expect to become pregnant, breastfeed, or plan to donate eggs during the trial or within 30 days of the last dose of trial drug
19. Current alcohol/substance abuse/dependence, history of alcohol/substance abuse/dependence within 12 months prior to randomization, or evidence of ongoing alcohol/substance abuse/dependence in the opinion of the trial administrator
20. Have undergone major surgery within 4 months before randomization, or plan or are scheduled to undergo any elective surgery or major dental surgery during the trial
21. Have a history of major organ transplantation (e.g. heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation
22. Developed malignancy within 5 years of randomization
23. Must stay in an institution pursuant to an order issued by a judicial or administrative authority
1. Have cold antibody AIHA, cold agglutinin syndrome, mixed (i.e., warm-cold) AIHA, or paroxysmal cold hemoglobinuria
Any other relevant cause of hereditary or acquired hemolytic anemia
3. Applicable to RCP (Part B) only, patients with secondary wAIHA not caused by autoimmune disease (including LPD)
4. Received blood transfusion within 2 weeks before random assignment
5. Use of B-cell depletion, B-cell targeting, or other biological immunomodulators within 6 months prior to randomization. Patients who have received B-cell-targeted therapy within 6 to 12 months prior to randomization must have a B-cell count measured by a central laboratory at screening that falls within the laboratory reference range
6. Received intravenous (IV) Ig or epoetin alfa within 6 weeks before randomization. Patients can be rescreened after the 6-week exclusion period
7. Receiving more than two concomitant medications used to treat wAIHA at the time of screening, excluding vitamins or other supplements
8. Received experimental treatment or direct medical intervention in another clinical trial within 12 weeks before screening or <5 half-lives of the experimental treatment, whichever is shorter
9. Received live vaccine or active therapeutic infectious agent within 6 weeks before randomization
10. Evidence of open tuberculosis (TB) or being at high risk for TB based on at least one of the following:
a. History of open TB or latent TB unless there is a record of completion of treatment according to local guidelines
b. The interferon-γ release assay result during screening is judged to be positive, uncertain or invalid, unless there is a treatment record. Patients with inconclusive test results can be tested again centrally or locally, but if repeated testing is still inconclusive, the patient will be excluded
c. Symptoms and signs that may represent open TB
d. Possible diagnosis of TB on chest radiography, computed tomography, or magnetic resonance imaging
11. Have a history or evidence of a clinically unstable/poorly controlled disorder, condition or disease (including but not limited to cardiopulmonary, oncological, renal, liver, metabolic, hematological, psychiatric, open infection) that the trial moderator believes will be safe for the patient pose a risk, or interfere with trial evaluation, procedures or completion
12. Known hypersensitivity to mAb therapy
13. Known allergy to dextran or dextran components
14. Have an open infection requiring parenteral or oral anti-infective drugs and/or hospitalization (e.g. pneumonia, biliary tract infection, diverticulitis, Clostridium difficile infection) within 8 weeks before screening, and/or have been diagnosed by the trial Moderator assessed as severe/clinically significant. Patients may be rescreened after the 8-week exclusion period.
15. Chronic infection (for example: bronchiectasis, chronic osteomyelitis, chronic pyelonephritis) or the need for long-term anti-infective treatment (for example: antibiotics, antiviral drugs)
16. Confirmed or suspected clinical immunodeficiency syndrome unrelated to wAIHA treatment, or a family history of congenital or hereditary immunodeficiency, unless it is confirmed that the patient does not suffer from the above-mentioned diseases
17. Acute hepatitis B infection (positive hepatitis B surface antigen), active hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. Patients will be excluded from the trial if there is a positive test result for active hepatitis B by detection of hepatitis B surface antigen. In Japan, patients were excluded if (a) hepatitis B surface antigen or (b) hepatitis B surface antibody or (c) hepatitis B core antibody was detected. Patients with a history of HCV will be excluded from the trial unless there is data showing negative serum HCV ribonucleic acid concentrations 12 weeks or more after completion of HCV therapy
18. Expect to become pregnant, breastfeed, or plan to donate eggs during the trial or within 30 days of the last dose of trial drug
19. Current alcohol/substance abuse/dependence, history of alcohol/substance abuse/dependence within 12 months prior to randomization, or evidence of ongoing alcohol/substance abuse/dependence in the opinion of the trial administrator
20. Have undergone major surgery within 4 months before randomization, or plan or are scheduled to undergo any elective surgery or major dental surgery during the trial
21. Have a history of major organ transplantation (e.g. heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow transplantation
22. Developed malignancy within 5 years of randomization
23. Must stay in an institution pursuant to an order issued by a judicial or administrative authority
The Estimated Number of Participants
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Taiwan
5 participants
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Global
134 participants
