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

Official title

A Randomized, Multi-Center, Parallel, Double-Blinded, Placebo-Controlled Clinical Trial to Evaluate Efficacy, Safety, and Pharmacokinetics of XEMBIFY® Plus Standard Medical Treatment Compared to Placebo Plus Standard Medical Treatment to Prevent Infections in Patients With Hypogammaglobulinemia and Recurrent or Severe Infections Associated With B-cell Chronic Lymphocytic Leukemia, Multiple Myeloma, and Non-Hodgkin Lymphoma

Overview

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.

Interventions

• Drug Xembify
  SC infusion pump
• Drug Placebo
  SC infusion pump

Primary outcome measures

• Annual Rate of Major Bacterial Infections per Year [Time frame: Up to Week 51]

Secondary outcome measures (12)

• Time to First Onset of Major Bacterial Infection [Time frame: Up to Week 51]
• Percentage of Participants who Experience Major Bacterial Infections [Time frame: Up to Week 51]
• Rate of all Bacterial Infections Determined by the Investigator [Time frame: Up to Week 51]
• Percentage of Participants who Experience Bacterial Infections [Time frame: Up to Week 51]
• Time to First Onset of Non-Major Bacterial Infections [Time frame: Up to Week 51]
• Number of Days on Which Participants Were on Antibiotics [Time frame: Up to Week 51]
• Number of Hospitalizations due to any Infections [Time frame: Up to Week 51]
• Duration of Hospitalizations due to any Infections [Time frame: Up to Week 51]
• Number of Hospitalizations due to Major Bacterial Infections [Time frame: Up to Week 51]
• Duration of Hospitalizations due to Major Bacterial Infections [Time frame: Up to Week 51]
• Rate of all Infections as Determined by the Investigator [Time frame: Up to Week 51]
• Number of Participants with Validated Infections [Time frame: Up to Week 51]

Eligibility criteria

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. (Note: For MM subjects, the IgG level is adjusted by subtracting the M-protein \[Mspike\] to reflect the true polyclonal IgG concentration.)
• 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 (allogenic transplant in the previous 24 months, and autologous transplant in the previous 3 months) before Screening visit.
• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Bulgaria · 14 centers

• GC2202 Study Site 202 — Burgas
• GC2202 Study Site 203 — Plovdiv
• GC2202 Study Site 210 — Plovdiv
• GC2202 Study Site 205 — Rousse
• GC2202 Study Site 209 — Sofia
• GC2202 Study Site 201 — Sofia
• GC2202 Study Site 206 — Sofia
• GC2202 Study Site 207 — Sofia
• … and 6 more centers

Poland · 11 centers

• GC2202 Study Site 402 — Torun
• GC2202 Study Site 401 — Krakow
• GC2202 Study Site 401 — Krakow
• GC2202 Study Site 403 — Legnica
• GC2202 Study Site 406 — Wałbrzych
• GC2202 Study Site 406 — Wałbrzych
• GC2202 Study Site 405 — Słupsk
• GC2202 Study Site 408 — Bydgoszcz
• … and 3 more centers

Romania · 10 centers

• GC2202 Study Site 511 — Bucharest
• GC2202 Study Site 501 — Bucharest
• GC2202 Study Site 503 — Brasov
• GC2202 Study Site 504 — Bucharest
• GC2202 Study Site 506 — Cluj-Napoca
• GC2202 Study Site 502 — Timișoara
• GC2202 Study Site 509 — Bucharest
• GC2202 Study Site 508 — Bucharest
• … and 2 more centers

Hungary · 8 centers

• GC2202 Study Site 305 — Székesfehérvár
• GC2202 Study Site 301 — Budapest
• GC2202 Study Site 308 — Budapest
• GC2202 Study Site 306 — Debrecen
• GC2202 Study Site 304 — Eger
• GC2202 Study Site 302 — Győr
• GC2202 Study Site 307 — Szeged
• GC2202 Study Site 303 — Szekszárd

United States · 7 centers

• GC2202 Study Site 115 — Huntington Park
• GC2202 Study Site 103 — St. Petersburg
• GC2202 Study Site 111 — Bethesda
• GC2202 Study Site 109 — Greenville
• GC2202 Decentralized Study Site 114 — Morrisville
• GC2202 Study Site 105 — Canton
• GC2202 Study Site 110 — Rockville

Serbia · 7 centers

• GC2202 Study Site 602 — Belgrade
• GC2202 Study Site 604 — Belgrade
• GC2202 Study Site 605 — Belgrade
• GC2202 Study Site 607 — Belgrade
• GC2202 Study Site 603 — Kamenitz
• GC2202 Study Site 601 — Kragujevac
• GC2202 Study Site 606 — Niš

Bosnia and Herzegovina · 3 centers

• GC2202 Study Site 702 — Banja Luka
• GC2202 Study Site 703 — Mostar
• GC2202 Study Site 701 — Sarajevo

Croatia · 2 centers

• GC2202 Study Site 801 — Rijeka
• GC2202 Study Site 802 — Zagreb

Identifiers

NCT: NCT05645107 · GC2202 · XEMBIFY® - CLL, MM, and NHL · 2022-502193-16-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗