Clinical trial NCT05645107: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hypogammaglobulinemia
Bacterial Infections
B-cell Chronic Lymphocytic Leukemia
Multiple Myleoma
Non-Hodgkin Lymphoma
Keywords: XEMBIFY
CLL
SMT
Hypogammaglobulinemia (HGG)
MM
NHL
Lead sponsor: Grifols Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2022-12-09
Enrollment: 386
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.
* 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 (\&amp;amp;lt;) 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).

Primary outcomes:
measure: Annual Rate of Major Bacterial Infections per Year
timeFrame: Up to Week 51
Secondary outcomes:
measure: Time to First Onset of Major Bacterial Infection
timeFrame: Up to Week 51
measure: Percentage of Participants who Experience Major Bacterial Infections
timeFrame: Up to Week 51
measure: Rate of all Bacterial Infections Determined by the Investigator
timeFrame: Up to Week 51
measure: Percentage of Participants who Experience Bacterial Infections
timeFrame: Up to Week 51
measure: Time to First Onset of Non-Major Bacterial Infections
timeFrame: Up to Week 51
measure: Number of Days on Which Participants Were on Antibiotics
timeFrame: Up to Week 51
measure: Number of Hospitalizations due to any Infections
timeFrame: Up to Week 51
measure: Duration of Hospitalizations due to any Infections
timeFrame: Up to Week 51
measure: Number of Hospitalizations due to Major Bacterial Infections
timeFrame: Up to Week 51
measure: Duration of Hospitalizations due to Major Bacterial Infections
timeFrame: Up to Week 51
measure: Rate of all Infections as Determined by the Investigator
timeFrame: Up to Week 51
measure: Number of Participants with Validated Infections
timeFrame: Up to Week 51
measure: Time to First Onset of any Infection
timeFrame: Up to Week 51
Other outcomes:
Locations:
city: Saint Petersburg
country: United States
facility: GC2202 Study Site 103
state: Florida
city: Greenville
country: United States
facility: GC2202 Study Site 109
state: North Carolina
city: Morrisville
country: United States
facility: GC2202 Decentralized Study Site 114
state: North Carolina
city: Canton
country: United States
facility: GC2202 Study Site 105
state: Ohio
city: Rockville
country: United States
facility: GC2202 Study Site 110
state: South Carolina
city: Banja Luka
country: Bosnia and Herzegovina
facility: GC2202 Study Site 702
city: Mostar
country: Bosnia and Herzegovina
facility: GC2202 Study Site 703
city: Sarajevo
country: Bosnia and Herzegovina
facility: GC2202 Study Site 701
city: Burgas
country: Bulgaria
facility: GC2202 Study Site 202
city: Plovdiv
country: Bulgaria
facility: GC2202 Study Site 203
city: Plovdiv
country: Bulgaria
facility: GC2202 Study Site 210
city: Ruse
country: Bulgaria
facility: GC2202 Study Site 205
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 209
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 201
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 206
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 207
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 211
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 212
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 213
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 204
city: Sofia
country: Bulgaria
facility: GC2202 Study Site 208
city: Stara Zagora
country: Bulgaria
facility: GC2202 Study Site 214
city: Szekesfehervar
country: Hungary
facility: GC2202 Study Site 305
state: Fejer
city: Budapest
country: Hungary
facility: GC2202 Study Site 301
city: Budapest
country: Hungary
facility: GC2202 Study Site 308
city: Debrecen
country: Hungary
facility: GC2202 Study Site 306
city: Eger
country: Hungary
facility: GC2202 Study Site 304
city: Győr
country: Hungary
facility: GC2202 Study Site 302
city: Szeged
country: Hungary
facility: GC2202 Study Site 307
city: Szekszárd
country: Hungary
facility: GC2202 Study Site 303
city: Walbrzych
country: Poland
facility: GC2202 Study Site 406
state: Dolnoslaskie
city: Legnica
country: Poland
facility: GC2202 Study Site 403
state: Dolnośląskie
city: Wałbrzych
country: Poland
facility: GC2202 Study Site 406
state: Dolnośląskie
city: Toruń
country: Poland
facility: GC2202 Study Site 402
state: Kujawsko-pomorskie
city: Kraków
country: Poland
facility: GC2202 Study Site 401
state: Malopolskie
city: Kraków
country: Poland
facility: GC2202 Study Site 401
state: Małopolskie
city: Słupsk
country: Poland
facility: GC2202 Study Site 405
state: Pomorskie
city: Bydgoszcz
country: Poland
facility: GC2202 Study Site 408
city: Kraków
country: Poland
facility: GC2202 Study Site 410
city: Olsztyn
country: Poland
facility: GC2202 Study Site 409
city: Toruń
country: Poland
facility: GC2202 Study Site 407
city: Brasov
country: Romania
facility: GC2202 Study Site 503
state: RO
city: Bucuresti
country: Romania
facility: GC2202 Study Site 504
state: RO
city: Cluj-Napoca
country: Romania
facility: GC2202 Study Site 506
state: RO
city: Timisoara
country: Romania
facility: GC2202 Study Site 502
state: RO
city: Bucharest
country: Romania
facility: GC2202 Study Site 509
city: Bucharest
country: Romania
facility: GC2202 Study Site 508
city: Bucharest
country: Romania
facility: GC2202 Study Site 501
city: Constanţa
country: Romania
facility: GC2202 Study Site 507
city: Iaşi
country: Romania
facility: GC2202 Study Site 510
city: Belgrade
country: Serbia
facility: GC2202 Study Site 602
city: Belgrade
country: Serbia
facility: GC2202 Study Site 605
city: Belgrade
country: Serbia
facility: GC2202 Study Site 607
city: Belgrad
country: Serbia
facility: GC2202 Study Site 604
city: Kragujevac
country: Serbia
facility: GC2202 Study Site 601
city: Nis
country: Serbia
facility: GC2202 Study Site 606
city: Sremska Kamenica
country: Serbia
facility: GC2202 Study Site 603
Study officials:
References: