Efficacy and Safety of M281 in Adults with Warm Autoimmune Hemolytic Anemia
- Conditions
- Adults with Warm Autoimmune Hemolytic AnemiaMedDRA version: 20.0Level: LLTClassification code 10073784Term: Anemia hemolytic autoimmuneSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-000720-17-HU
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 148
DBP
1. Male or female =18 years of age.
2. Diagnosed with active primary or secondary wAIHA, defined as:
a.Hemoglobin concentration <9 g/dL or <10 g/dL if symptomatic or on corticosteroids/immunosuppressants AND
b.Signs of hemolysis, defined as: lactate dehydrogenase (LDH) levels above upper limit of normal (ULN), or haptoglobin below lower limit of normal, or indirect bilirubin above ULN AND
c.Serological evidence of anti-erythrocyte antibodies associated with a DAT that is either positive for IgG only or is positive for IgG+C3d at screening. DAT: negative, can be repeated once. If negative, patient not eligible.
3.Diagnosed with wAIHA for at least 3 months, and currently receiving or previously received treatment for wAIHA (treatment naive patients not eligible)
4.If on corticosteroids, the dose must be stable during screening or for at least 14 d prior randomization.
5. If receiving immunosuppressants, following drugs allowed: concomitant immunosuppressants are azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, cyclosporine, tacrolimus, danazol, and cyclophosphamide. Patient on stable dose of these drugs for =12 weeks prior screening and during the screening period. If stopped, for at least 8 weeks prior to screening.
6.Have a platelet count =30 × 10E9/L.
7.Patients who have undergone splenectomy must be at least 3 months post resection prior screening and must be vaccinated as per the US Center for Disease Control and Prevention annual Recommended Immunization Schedule for Adults Aged 19 Years or Older, US
8.Patients with other autoimmune disease or lymphoproliferative disorders may be eligible if they are stable (no changes in concomitant disease-related medications and severity of disease for at least 3 months prior to screening). Patients with lymphoproliferative disease must have a low grade, be stable and be, unlikely to require chemotherapy or monoclonal antibody therapy during the double blind period of the study. Patients requiring change of treatment or new treatment (but not rescue therapy for wAIHA) during the DBP will be terminated from the study
9.Have sufficient venous access to allow drug administration by IV infusion and blood sampling as per the protocol.
10.Women of childbearing potential, defined as women physiologically capable of becoming pregnant, must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Baseline. Menopausal women must have an elevated serum FSH level at Screening; if the FSH is not elevated, they are considered to be of childbearing potential and must have a negative serum pregnancy test at screening and a negative urine pregnancy test at Baseline to be eligible.
11.Women of childbearing potential (including menopausal women who do not have elevated FSH) must agree to remain totally abstinent or to consistently use a reliable and highly effective method of contraception during the study and for 30 days after the last study treatment.
12.Male patients must agree to remain totally abstinent (ie, refrain from sexual intercourse during the study) or to consistently use a reliable and highly effective method of contraception (eg, condom plus diaphragm, condom plus spermicide, diaphragm plus spermicide, or intrauterine device or oral/injectable/implanted hormonal contraceptive used in combination with an additional barrier method) to avoid pregnancy of the patient's partner(s) during the study and for 100 days following the last study treatmen
Double blind period
1. Are currently taking IgG Fc-related protein therapeutics.
2.Have received transfusion within 30 days prior to randomization.
3.Have any other associated cause of hereditary or acquired hemolytic anemia.
4.Have received rituximab within 3 months prior to screening.
5.Have received IVIg within 6 weeks prior to screening.
6.Have cold antibody AIHA, cold agglutinin syndrome, mixed type (ie, warm and cold) AIHA, or paroxysmal cold hemoglobinuria.
7.Have a severe infection that requires parenteral anti-infectives and/or hospitalization, and/or is assessed as serious/clinically significant by the Investigator, within 8 weeks prior to screening. Any patient with an infection requiring oral antiinfectives within 4 weeks prior to screening will be excluded.
8.Have a chronic infection or require chronic treatment with anti-infectives.
9.Have received a live vaccine within 3 months prior to screening, or have a known need to receive a live vaccine during the study or within at least 3 months after the last dose of study drug.
10. Have any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her wAIHA, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the patient.
11.Have any of the following viral testing outcomes: A history of HIV infection or positive test result for HIV-1 and HIV 2 antibodies; positive test for hepatitis B virus surface antigen. For patients with a negative test for HBsAg along with a positive test for anti-hepatitis B core antibodies and a positive or negative test for anti-HBs antibodies, hepatitis B viral DNA detection will be performed. Patients with a positive hepatitis B viral DNA detection will be excluded; A positive test for hepatitis C virus (HCV) antibodies along with a positive detection for HCV RNA.
12.Are currently breastfeeding, pregnant, intend to become pregnant during the study, or are planning egg donation during the study or within 30 days after the last dose of study drug.
13.Have current alcohol/substance abuse/dependence, a history of alcohol/substance abuse/dependence within the 12 months prior to screening, or, in the Investigator's opinion, show evidence of ongoing alcohol/substance abuse/dependence.
14.Are currently participating in another interventional clinical trial or have received any investigational drug within the past 3 months prior to screening.
15.Have had any major surgery within 3 months prior to screening or have plans for or have been scheduled for any elective surgery or major dental procedure during the study.
16.Have a history of a major organ transplant, or hematopoietic stem cell/marrow transplant.
17.Have a history of severe and/or uncontrolled hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological, or musculoskeletal disorder, hypertension, or any other medical or uncontrolled autoimmune disorder that, in the opinion of the Investigator, might interfere with the patient's full participation in the study, or might jeopardize the safety of the patient or the validity of the study results.
18.Received treatment for non-lymphoid malignancy within 1 year prior to screening, with the exceptions of properly treated basal or squamous cell carcinoma of the skin or properly treated carcinoma in situ of the cervix.
19. Have any other medical condition(s) likely to require treatment with oral or parenteral glucocorticosteroids, or have required oral or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method