Efficacy and Safety of M281 in Adults with Warm Autoimmune Hemolytic Anemia: A Multicenter, Randomized, Double blind, Placebo controlled Study with a Long-term Open-label Extensio

Phase 2

Recruiting

• Conditions: wAIHA; Warm Autoimmune Hemolytic Anemia; 10018911; 10003816

• Registration Number: NL-OMON54686
• Lead Sponsor: Janssen-Cilag International NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 9 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 6

Inclusion Criteria

Inclusion Criteria, Double-blind Period
Patients who meet the following criteria will be eligible for enrollment into
the double-blind period of the study.
1. Male or female >=18 years of age.
2. Diagnosed with active primary or secondary wAIHA, defined as having all of
the following:
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 (fragment
of the third component of complement) at screening at the central laboratory.
If the DAT is negative, it can be repeated once. If the repeat is negative,
participant not eligible.
3. Have been diagnosed with wAIHA for at least 3 months, and are currently
receiving treatment for wAIHA OR have previously received treatment for wAIHA
(treatment-naïve participants are 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 must have
been on a stable dose of any of
these drugs for =12 weeks prior to screening and during the screening period.
If any of these drugs were stopped,
it must have been 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 × 109/L.
Note: Patients with Evans syndrome who do not have primary immunodeficiency
will be eligible as long as they meet all other entry criteria, including
having a platelet count >=30 × 109/L.
7. Participants who have undergone splenectomy must be at least 3 months post
resection prior to screening and must be vaccinated as per the United States
Center for Disease Control and Prevention (CDC) annual Recommended Immunization
Schedule for Adults Aged 19 Years or Older, United States
(https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html) OR must
be vaccinated as per country-specific guidelines (Davies 2011).
8. Participants with other autoimmune disease (e.g., systemic lupus
erythematosus or rheumatoid arthritis) 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 also have a low grade, be
stable and be, in the opinion of the Investigator, 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

Exclusion Criteria

Exclusion Criteria, Double-blind Period
Patients who meet any of the following criteria will not be eligible for
enrollment into the double-blind period of the study.
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 (i.e., warm and cold) AIHA, or paroxysmal cold hemoglobinuria.
7. Have a severe infection (e.g., pneumonia, biliary tract infection,
diverticulitis, Clostridium difficile infection) that requires parenteral
anti-infectives and/or hospitalization, and/or is assessed as
serious/clinically significant (CS) by the Investigator, within 8 weeks prior
to screening. Any participant with an infection requiring oral anti-infectives
(e.g., sinusitis, bronchitis, uncomplicated urinary tract infection) within 4
weeks prior to screening will be excluded.
8. Have a chronic infection (e.g., bronchiectasis, chronic osteomyelitis,
chronic pyelonephritis) or require chronic treatment with anti-infectives
(e.g., 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 human immunodeficiency virus (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 (HBc) 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 <

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Durable response in improvement in hemoglobin (Hgb), defined as attainment of<br /><br>the following at 3 consecutive visits (minimum duration 28 days) , where at<br /><br>least the first is at or before Week 16, without the need of rescue therapy:<br /><br>• Hgb concentration >=10 g/dL AND<br /><br>• An increase from baseline in Hgb >=2 g/dL</p><br>