Efficacy and Safety of M281 in Adults with Warm Autoimmune Hemolytic Anemia

Phase 1

• Conditions: Adults with Warm Autoimmune Hemolytic Anemia; MedDRA version: 20.1Level: LLTClassification code 10002285Term: Anemia hemolytic autoimmune (NOS)System Organ Class: 100000004851; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2019-000720-17-NL
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-09-16
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 148

Inclusion Criteria

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 the upper limit of normal (ULN), or haptoglobin below the lower limit of normal, or indirect bilirubin above the 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 and 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 has 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 to screening and must be vaccinated as per CDC annual Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States
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 (incl. 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 dose of study drug.
12.Male participants must wear a condom when engaging in any activity that allows for passage of ejaculate to another

Exclusion Criteria

Double blind period
1.Are currently taking IgG Fc-related protein therapeutics.
2.Have received a 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 anti-infectives within 4 weeks prior to screening will be excluded.
8.Have a chronic infection or require chronic treatment with anti-infectives (eg, antibiotics, antivirals).
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 3 months after the last dose of study drug. For information regarding the Bacille Calmette-Guérin (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; A positive test for hepatitis B virus surface antigen (HBsAg). 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 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.

Opel Label Extension
1.Met any of the stopping criteria (see Section 6.4.1 of

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified