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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

Phase 3
Recruiting
Conditions
Hypogammaglobulinemia
Bacterial Infections
B-cell Chronic Lymphocytic Leukemia
Multiple Myleoma
Non-Hodgkin Lymphoma
Interventions
Drug: Placebo
Registration Number
NCT05645107
Lead Sponsor
Grifols Therapeutics LLC
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
386
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 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).

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
XEMBIFY + Standard Medical Treatment (SMT)XembifyParticipants 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.
Placebo + SMTPlaceboParticipants 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.
Primary Outcome Measures
NameTimeMethod
Annual Rate of Major Bacterial Infections per YearUp to Week 51
Secondary Outcome Measures
NameTimeMethod
Rate of all Infections as Determined by the InvestigatorUp to Week 51
Time to First Onset of Major Bacterial InfectionUp to Week 51
Percentage of Participants who Experience Major Bacterial InfectionsUp to Week 51
Rate of all Bacterial Infections Determined by the InvestigatorUp to Week 51
Percentage of Participants who Experience Bacterial InfectionsUp to Week 51
Time to First Onset of Non-Major Bacterial InfectionsUp to Week 51
Number of Days on Which Participants Were on AntibioticsUp to Week 51
Number of Hospitalizations due to any InfectionsUp to Week 51
Duration of Hospitalizations due to any InfectionsUp to Week 51
Number of Hospitalizations due to Major Bacterial InfectionsUp to Week 51
Duration of Hospitalizations due to Major Bacterial InfectionsUp to Week 51
Number of Participants with Validated InfectionsUp to Week 51
Time to First Onset of any InfectionUp to Week 51

Trial Locations

Locations (55)

GC2202 Study Site 701

🇧🇦

Sarajevo, Bosnia and Herzegovina

GC2202 Decentralized Study Site 114

🇺🇸

Morrisville, North Carolina, United States

GC2202 Study Site 211

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 213

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 702

🇧🇦

Banja Luka, Bosnia and Herzegovina

GC2202 Study Site 703

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Mostar, Bosnia and Herzegovina

GC2202 Study Site 212

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 408

🇵🇱

Bydgoszcz, Poland

GC2202 Study Site 507

🇷🇴

Constanţa, Romania

GC2202 Study Site 510

🇷🇴

Iaşi, Romania

GC2202 Study Site 605

🇷🇸

Belgrade, Serbia

GC2202 Study Site 607

🇷🇸

Belgrade, Serbia

GC2202 Study Site 214

🇧🇬

Stara Zagora, Bulgaria

GC2202 Study Site 410

🇵🇱

Kraków, Poland

GC2202 Study Site 509

🇷🇴

Bucharest, Romania

GC2202 Study Site 409

🇵🇱

Olsztyn, Poland

GC2202 Study Site 407

🇵🇱

Toruń, Poland

GC2202 Study Site 508

🇷🇴

Bucharest, Romania

GC2202 Study Site 103

🇺🇸

Saint Petersburg, Florida, United States

GC2202 Study Site 109

🇺🇸

Greenville, North Carolina, United States

GC2202 Study Site 105

🇺🇸

Canton, Ohio, United States

GC2202 Study Site 110

🇺🇸

Rockville, South Carolina, United States

GC2202 Study Site 202

🇧🇬

Burgas, Bulgaria

GC2202 Study Site 203

🇧🇬

Plovdiv, Bulgaria

GC2202 Study Site 210

🇧🇬

Plovdiv, Bulgaria

GC2202 Study Site 205

🇧🇬

Ruse, Bulgaria

GC2202 Study Site 209

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 201

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 206

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 207

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 204

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 208

🇧🇬

Sofia, Bulgaria

GC2202 Study Site 305

🇭🇺

Szekesfehervar, Fejer, Hungary

GC2202 Study Site 301

🇭🇺

Budapest, Hungary

GC2202 Study Site 308

🇭🇺

Budapest, Hungary

GC2202 Study Site 306

🇭🇺

Debrecen, Hungary

GC2202 Study Site 304

🇭🇺

Eger, Hungary

GC2202 Study Site 302

🇭🇺

Győr, Hungary

GC2202 Study Site 307

🇭🇺

Szeged, Hungary

GC2202 Study Site 303

🇭🇺

Szekszárd, Hungary

GC2202 Study Site 406

🇵🇱

Wałbrzych, Dolnośląskie, Poland

GC2202 Study Site 403

🇵🇱

Legnica, Dolnośląskie, Poland

GC2202 Study Site 402

🇵🇱

Toruń, Kujawsko-pomorskie, Poland

GC2202 Study Site 401

🇵🇱

Kraków, Małopolskie, Poland

GC2202 Study Site 405

🇵🇱

Słupsk, Pomorskie, Poland

GC2202 Study Site 503

🇷🇴

Brasov, RO, Romania

GC2202 Study Site 504

🇷🇴

Bucuresti, RO, Romania

GC2202 Study Site 506

🇷🇴

Cluj-Napoca, RO, Romania

GC2202 Study Site 502

🇷🇴

Timisoara, RO, Romania

GC2202 Study Site 501

🇷🇴

Bucharest, Romania

GC2202 Study Site 602

🇷🇸

Belgrade, Serbia

GC2202 Study Site 604

🇷🇸

Belgrad, Serbia

GC2202 Study Site 601

🇷🇸

Kragujevac, Serbia

GC2202 Study Site 606

🇷🇸

Nis, Serbia

GC2202 Study Site 603

🇷🇸

Sremska Kamenica, Serbia

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