NIPOCALIMAB for Warm autoimmune hemolytic anemia

Inclusion criteria

• {"criterion_text":"- Double blind period - 1.Participants ≥18 years of age"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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 study drug."}
• {"criterion_text":"- Male participants must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for at least 90 days after receiving the last dose of study drug. In addition, male participants with partners who are a woman of childbearing potential are to be highly encouraged to inform their partner to use highly effective contraception methods that result in a low failure rate (less than 1% per year)"}
• {"criterion_text":"- Participants who use herbal, naturopathic, traditional Chinese remedies, ayurvedic and nutritional supplements, or medical marijuana (with a doctor's prescription) are eligible if the use of these medications is acceptable to the Investigator. These remedies must be at a stable dose and regimen using the same preparation for ≥2 months prior to Screening."}
• {"criterion_text":"- Are able to understand and voluntarily provide written informed consent to participate in the study and comply with all study procedures."}
• {"criterion_text":"- Vaccinations prior to screening as per routine local guidelines (including COVID-19)"}
• {"criterion_text":"- Open-Label 1. Have completed the double-blind period (through Week 24), or have required rescue therapy at/or after Week 4 of the double-blind period, or failed to demonstrate an increase from baseline in Hgb of at least 1 g/dL and are symptomatic at or after Week 16 of the double-blind period."}
• {"criterion_text":"- 2. Are able to understand and voluntarily provide written informed consent to participate in the OLE period and comply with all study procedures."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Diagnosed with wAIHA for at least 3 months, and currently receiving or previously received treatment for wAIHA (treatment naïve participants not eligible)"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have a platelet count ≥30 × 10E9/L."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have sufficient venous access to allow drug administration by IV infusion and blood sampling as per the protocol."}

Exclusion criteria

• {"criterion_text":"- Double-blind period 1.Are currently taking IgG Fc-related protein therapeutics."}
• {"criterion_text":"- Have any other associated cause of hereditary or acquired hemolytic anemia."}
• {"criterion_text":"- Have received rituximab within 3 months prior to screening"}
• {"criterion_text":"- Have received IVIg within 6 weeks prior to screening"}
• {"criterion_text":"- Have been diagnosed with cold antibody AIHA, cold agglutinin syndrome, mixed type (ie, warm and cold) AIHA, or paroxysmal cold hemoglobinuria."}
• {"criterion_text":"- 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 (eg, sinusitis, bronchitis, uncomplicated urinary tract infection) within 4 weeks prior to screening will be excluded"}
• {"criterion_text":"- Have a chronic infection or require chronic treatment with anti-infectives."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Open Label Extension 1. Met any of the stopping criteria or discontinued study drug during the double-blind period due to treatment- related AE."}
• {"criterion_text":"- Currently have a serious or clinically significant infection requiring parenteral anti-infectives and/or hospitalization. The following exclusion criterion from the Double-blind Period also applies to enrollment in the OLE: Exclusion Criteria #8 and #21. Exception: Participants who were previously enrolled in this study and unable to complete the double-blind period due to the Sponsor suspending dosing due to the COVID-19 pandemic can be enrolled in the OLE after meeting all of the double-blind eligibility criteria. Participants who completed the 28-week OLE before Amendment 6 can be re-enrolled in the OLE per investigator's discretion if the participants continue meet the eligibility criteria for the OLE. Participants will resume study treatment calculated from the baseline visit once they have reconsented to the study."}
• {"criterion_text":"- Have any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of their wAIHA or have a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Are currently participating in another interventional clinical trial or have received any investigational drug within the past 3 months prior to screening."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have a history of a major organ transplant, or hematopoietic stem cell/marrow transplant."}
• {"criterion_text":"- Have received a transfusion within 30 days prior to randomization."}

Primary endpoints

• {"endpoint_text":"- The primary efficacy endpoint is durable response in improvement of Hgb, defined as the attainment of the following at 3 consecutive visits (minimum duration 28 days), where at least the first is at or before Week 16, without the need of rescue therapy: • Hgb concentration ≥10 g/dL AND • An increase from baseline in Hgb ≥2 g/dL The first of the three consecutive visits must be at or before week 16 of the double-blind period in order to qualify for success in the primary efficacy endpoint.","definition_or_measurement_approach":"Durable response defined as Hgb ≥10 g/dL AND increase from baseline ≥2 g/dL at 3 consecutive visits (minimum duration 28 days), with the first of the three visits at or before Week 16, without need for rescue therapy."}
• {"endpoint_text":"- (Cont.) For example, if a participant attained the above criteria at weeks 18, 20, and 22 and not before, this participant would not be considered a success. If the participant attained the criteria at weeks 16, 18, and 20, the patient would be considered a success. Participants who took rescue therapy before reaching the criteria will be treated as having failed the primary efficacy outcome.","definition_or_measurement_approach":"Clarification: the first of the three qualifying visits must be at or before Week 16. Participants receiving rescue therapy before meeting the criteria are considered failures for the primary endpoint."}
• {"endpoint_text":"- (Cont.) . If a participant has missing Hgb at both screening and baseline but is randomized by mistake, the participant will be excluded from the ITT analysis. This situation is unlikely to happen because the IVRS system requires screening Hgb for randomization to occur","definition_or_measurement_approach":"Handling rule: participants missing Hgb at both screening and baseline but randomized in error will be excluded from ITT; IVRS requires screening Hgb for randomization."}

Methods

• Print advertisements: study-specific print ads and posters (K2/K1 recruitment materials) targeted to potential patient participants (adults with wAIHA).
• Flyers and brochures: participant recruitment flyers, brochures and study fact sheets (K2 materials) for patients and caregivers.
• Clinical trial education booklets: educational materials for potential participants (K2 clinical trial education booklets).
• Web advertising: web ads and online recruitment materials (K2_Patient Web Ad) used to reach potential participants.
• Participant ID cards and patient materials: patient ID cards and placebo information sheets provided as part of recruitment/participant materials.
• Country-localised materials: recruitment materials and informed consent/participant information were produced for and associated with multiple Member States (documents in the record associated with Greece, Hungary, Netherlands, Poland, Spain, France, Germany, Czechia, Italy)

Greece

Earliest CTIS Part Ii Submission Date

12-03-2024

Latest Decision Or Authorization Date

07-10-2024

Processing Time Days

209

Number Of Sites

3

Number Of Participants

3

Hungary

Earliest CTIS Part Ii Submission Date

04-01-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

767

Number Of Sites

4

Number Of Participants

7

Netherlands

Earliest CTIS Part Ii Submission Date

04-01-2024

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

798

Number Of Sites

2

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

06-02-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

734

Number Of Sites

4

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

04-01-2024

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

768

Number Of Sites

10

Number Of Participants

10

France

Earliest CTIS Part Ii Submission Date

04-01-2024

Latest Decision Or Authorization Date

06-02-2026

Processing Time Days

764

Number Of Sites

2

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

24-01-2024

Latest Decision Or Authorization Date

11-02-2026

Processing Time Days

749

Number Of Sites

2

Number Of Participants

3

Czechia

Earliest CTIS Part Ii Submission Date

04-01-2024

Latest Decision Or Authorization Date

09-02-2026

Processing Time Days

767

Number Of Sites

1

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

04-01-2024

Latest Decision Or Authorization Date

10-02-2026

Processing Time Days

768

Number Of Sites

4

Number Of Participants

15

Primary sponsor

Full Name

Janssen - Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

Sponsor duties codes: 1,12,2,6 (as listed in CTIS record)

Third parties

• {"country":"United States","full_name":"Arup Laboratories Inc.","duties_or_roles":"Haptoglobin and Urine Myoglobin","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Sponsor duties codes: 1, 12, 2, 6 (as listed in CTIS record)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medpace Reference Laboratories LLC","duties_or_roles":"FSH,Serum ßHCG, Creatinine Phosphokinase Isoenzyme; Primary/ surrogate endpoint test","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Versiti Wisconsin Inc.","duties_or_roles":"Monospecific DAT","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"FSH,Serum ßHCG, Creatinine Phosphokinase Isoenzyme, Hemoglobine; Primary/ surrogate endpoint test","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG analysis / review","organisation_type":"Pharmaceutical company"}