Efficacy and Safety of M281 in Adults with Warm Autoimmune Hemolytic Anemia
- Conditions
- Adults with Warm Autoimmune Hemolytic AnemiaMedDRA version: 20.1Level: LLTClassification code 10002285Term: Anemia hemolytic autoimmune (NOS)System Organ Class: 100000004851Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2019-000720-17-GR
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 148
Double blind period
1.Participants =18 years of age.2. Diagnosed with active primary or secondary wAIHA, defined as:
a. Hgb value<10 g/dL 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, participant not eligible.3.Diagnosed with wAIHA for at least 3 months, and currently receiving or previously received treatment for wAIHA (treatment naive participants not eligible) 4.If on corticosteroids, participants must have been on treatment for at least 4 weeks with a stable dose during the screening period or for at least 14 days prior to randomization, whichever is longer. Note:Investigators can optimize the above background medications prior to randomization if they are following the above rules for stable dose duration.5. If receiving immunosuppressants, following drugs allowed:concomitant immunosuppressants are azathioprine, mycophenolate
mofetil/mycophenolic acid, methotrexate, cyclosporine, tacrolimus,danazol, and cyclophosphamide. Participants 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. Note: Investigators can optimize the above background medications prior to randomization if they are following the above rules for stable dose duration. 6.Have a platelet count =30 × 10E9/L.
7.Participants 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.Participants 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). Participants 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.
Participants requiring change of treatment or new treatment for
autoimmune or lymphoproliferative diseases (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 (i.e.,
refrain from sexual intercourse during the study) or to consistently use a
reliable and highly effective method of contraception during the study
and for 30 days after the last dose of
drug.
study
12. Male participants must wear a condom when en
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 been diagnosed with 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 participant
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 viral or bacterial vaccine within 4 weeks prior to
first dose of study drug, or have a known need to receive a live viral or
bacterial vaccine during the study or within at least 8 weeks after the
last dose of study drug. For information regarding the Bacille CalmetteGuérin (BCG) vaccine, please see Exclusion Criterion
25.
10. Have any confirmed or suspected clinical immunodeficiency
syndrome not related to treatment of their wAIHA, or has a family
history of congenital or hereditary immunodeficiency unless confirmed
absent in the
participant.
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 participants 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. Participants with a
positive hepatitis B viral DNA detection will be excluded. If HBV DNA
testing cannot be performed, or there is evidence of chronic liver
disease, the participant is not eligible for the protocol; A positive test
for
hepatitis C virus (HCV) unless 1 of the following conditions are met: (a)
Has a history of successful treatment, defined as being negative for HCV
RNA at least 24 weeks after completing antiviral treatment, and has a
negative HCV RNA test result at screening, OR (b) -Has a negative HCV
RNA test result at least 24 weeks prior to screening and a negative HCV
RNA test at the
screening.
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.
Further exclusion criteria listed in the protocol not listed here due to
character restriction.
Open Label Extension
1. Met any of the st
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