A Study to Evaluate Efficacy, Safety, and PK of XEMBIFY®+Standard Medical Treatment (SMT) Compared to Placebo+SMT to Prevent Infections in Participants with HGG and Recurrent or Severe Infections Associated with B-cell Chronic Lymphocytic Leukemia, Multiple Myeloma, and Non-Hodgkin Lymphoma

Grifols

Status and phase: Enrolling; Phase 3

Conditions: Multiple Myleoma; Hypogammaglobulinemia; B-cell Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Bacterial Infections

Treatments: Drug: Xembify; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05645107

XEMBIFY® - CLL, MM, and NHL (Other Identifier)

GC2202

2022-502193-16-00 (Other Identifier)

Details and patient eligibility

About

The primary purpose of the study is to evaluate whether biweekly administered XEMBIFY® plus Standard Medical Treatment (SMT) over a one-year period will reduce the rate of major bacterial infections per participant per year in B-cell CLL, MM, and NHL participants with hypogammaglobulinemia (HGG) in comparison to the Placebo plus SMT group.

Enrollment: 386 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Participants ≥18 years of age at screening visit

• Participants with documented and confirmed diagnosis of any of the below diseases:

  • B-cell CLL according to International Workshop on CLL (iwCLL) criteria and RAI staging of intermediate (1 and 2) or high (3 and 4)
  • MM according to the International Myeloma Working Group criteria (IMWG), R-ISS stage II or, III; or
  • Histologically confirmed diagnosis of B-Cell NHL, Stage III or above (IV, Progressive/refractory, or recurrent/relapsed stage) according to the Lugano Classification.

• Participants with HGG with IgG levels less than 5 g/L.

• Participants with documented history of at least one severe bacterial infection (bacterial or viral) or recurrent bacterial/viral infections (that is., ≥ 3 infections) within 12 months before the screening visit. Severe bacterial/viral infections ≥ Grade 3 (as defined by Common Terminology Criteria for Adverse Events [CTCAE] Grades).

Exclusion criteria

• Participants with documented history of hematopoietic stem cell transplant.
• Participants currently receiving immunoglobulin replacement therapy (IgRT) or have received IgG replacement treatment (i.e., prior immune globulin replacement therapy) within 6 months before the screening visit.
• Participants with active infections at time of screening visit. Specific supportive anti-infective prophylactic defined in the CLL National Comprehensive Cancer Network (NCCN) or iwCLL guidelines and/or local/international guidelines for the CLL, and defined in local/international guidelines for MM and NHL are allowed, or recommended in the updated labelling of specific active target disease medicines used during the participation in the trial is also allowed.
• Participants with active second malignancies.
• Participants with known primary immunodeficiency (PI).
• Participants with a life expectancy less than 1.5 years.
• Participants with clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with successful completion of the trial or place the subject at undue medical risk.
• Participants have had a known serious adverse reaction (AR) to immunoglobulin or any anaphylactic reaction to blood or any blood-derived product.
• Participants have a history of blistering skin disease, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where SC therapy would be contraindicated during the study based upon the Investigator's discretion.
• Participants have known Selective Immunoglobulin A (IgA) Deficiency (with or without antibodies to IgA) (Note: exclusion is for the specific diagnostic entity. It does not exclude other forms of humoral primary immunodeficiency which have decreased IgA in addition to decreased IgG requiring IgG replacement).
• Participants with severe known kidney disease [as defined by estimated glomerular filtration rate [eGFR] less than (<) 30 milliliter (mL)/min/1.73 square meter (m2)] as determined by the Principal Investigator.
• Participants that have liver enzyme levels (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gammaglutamyl transferase [GGT], or lactate dehydrogenase [LDH]) greater than 3 times the upper limit of normal (ULN) at the Screening Visit as defined by the testing laboratory.
• Participants have a history (either 1 episode within the year prior to the Screening Visit or 2 previous episodes over a lifetime) of or current diagnosis of thromboembolism (example, myocardial infarction, cerebrovascular accident, or transient ischemic attack) or deep venous thrombosis.
• Participants are currently receiving anti-coagulation therapy which would make SC administration inadvisable (vitamin K antagonists, nonvitamin K antagonist oral anticoagulants [example, dabigatran etexilate targeting Factor IIa, rivaroxaban, edoxaban, and apixaban targeting Factor Xa], and parenteral anticoagulants [example, fondaparinux]).
• Participants currently have a known hyperviscosity syndrome or hypercoagulable states.
• Participants have a known previous infection or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection.
• Participants with non-controlled arterial hypertension (systolic blood pressure [SBP] greater than 140 millimeters of mercury (mmHg) and/or diastolic blood pressure [DBP] greater than 90 mmHg), and/or a heart rate (HR) greater than100 bpm.
• Participants with known substance or prescription drug abuse within 12 months before the Screening Visit.
• Participants have participated in another clinical trial within 30 days prior to screening (observational studies without investigative treatments [non-interventional] are permitted).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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386 participants in 2 patient groups, including a placebo group

XEMBIFY + Standard Medical Treatment (SMT)

Experimental group

Description:

Participants will receive a loading dose of 150 milligrams per kilograms per day (mg/kg/day) (Week 1, Days 1 to 5) subcutaneously (SC) for 5 consecutive daily doses followed by biweekly infusions of 300 mg/kg/2-week starting Week 3 (Day 15) through Week 51 (end of Treatment Phase). The SMT will include the active treatments and the other supportive treatments that the participants will need during their participation.

Treatment:

Drug: Xembify

Placebo + SMT

Placebo Comparator group

Description:

Participants will receive sterile 0.9 percent Sodium Chloride Injection (commercially available in the corresponding country) starting at Week 1 (Days 1 to 5) SC for 5 consecutive daily doses followed by biweekly infusions starting at Week 3 (Day 15) through Week 51. The SMT will include the active treatments and the other supportive treatments that the participants will need during their participation.

Treatment:

Drug: Placebo