A Study to Evaluate Efficacy, Safety, and Pharmacokinetics of XEMBIFY® Plus Standard Medical Treatment (SMT) Compared to Placebo Plus SMT to Prevent Infections in Participants With Hypogammaglobulinemia and Recurrent or Severe Infections Associated With B-cell Chronic Lymphocytic Leukemia

Bacterial Infections Clinical Trial

Official title:

A 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05645107
• Other study ID #: GC2202
• Secondary ID: XEMBIFY® - CLL20
• Status: Recruiting
• Phase: Phase 3
• Start date: December 26, 2022
• Est. completion date: June 2026

Study information

• Verified date: May 2024
• Source: Grifols Therapeutics LLC
• Contact: Terra Stockwell
• Phone: 019195649275
• Email: Terra.Stockwell[@]grifols.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary purpose of the study is to evaluate whether weekly 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 participants with hypogammaglobulinemia (HGG) associated with B-cell chronic lymphocytic leukemia (CLL) in comparison to the Placebo plus SMT group.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 386
• Est. completion date: June 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participants =18 years of age at screening

• Participants with documented and confirmed diagnosis of B-cell CLL according to International Workshop on CLL (iwCLL) criteria.

• Participants with hypogammaglobulinemia with immunoglobulin G (IgG) levels <4 grams per liter (g/L)

• Participants with RAI staging of intermediate (1 and 2) or high (3 and 4) as documented in the participant's medical history.

• Participants with documented history of at least one severe bacterial infection or recurrent bacterial infections (that is., = 3 infections) within 12 months before the screening visit. Severe bacterial 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 or receiving therapeutic or prophylactic antibiotic treatment at time of screening visit. Specific supportive anti-infective prophylactic defined in the CLL National Comprehensive Cancer Network (NCCN) or iwCLL guidelines or recommended in the updated labelling of specific antileukemic medicines used during the participation in the trial is 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 with 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] more than (>)140 millimeters of mercury (mmHg) and/or diastolic blood pressure [DBP] >90 mmHg), and/or a heart rate (HR) >100 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).

Related Conditions & MeSH terms

• Agammaglobulinemia
• B-cell Chronic Lymphocytic Leukemia
• Bacterial Infections
• Communicable Diseases
• Hypogammaglobulinemia
• Infections
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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

Locations

Country	Name	City	State
Bulgaria	GC2202 Study Site 202	Burgas
Bulgaria	GC2202 Study Site 210	Plovdiv
Bulgaria	GC2202 Study Site 205	Ruse
Bulgaria	GC2202 Study Site 201	Sofia
Bulgaria	GC2202 Study Site 204	Sofia
Bulgaria	GC2202 Study Site 206	Sofia
Bulgaria	GC2202 Study Site 207	Sofia
Bulgaria	GC2202 Study Site 208	Sofia
Bulgaria	GC2202 Study Site 209	Sofia
Poland	GC2202 Study Site 401	Kraków	Malopolskie
Poland	GC2202 Study Site 403	Legnica	Dolnoslaskie
Poland	GC2202 Study Site 405	Slupsk	Pomorskie
Poland	GC2202 Study Site 402	Torun	Kujawsko-pomorskie
Poland	GC2202 Study Site 406	Walbrzych	Dolnoslaskie
Romania	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
Serbia	GC2202 Study Site 602	Belgrade
Serbia	GC2202 Study Site 601	Kragujevac
Serbia	GC2202 Study Site 606	Nis
Serbia	GC2202 Study Site 603	Sremska Kamenica
United States	GC2202 Study Site 105	Canton	Ohio
United States	GC2202 Study Site 102	Columbus	Ohio
United States	GC2202 Study Site 108	Harlingen	Texas
United States	GC2202 Study Site 107	Miami	Florida
United States	GC2202 Study Site 101	Pittsburgh	Pennsylvania
United States	GC2202 Study Site 110	Rockville	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Grifols Therapeutics LLC

Countries where clinical trial is conducted

United States,  Bulgaria,  Poland,  Romania,  Serbia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annual Rate of Major Bacterial Infections per Year		Up to Week 53
Secondary	Time to First Onset of Major Bacterial Infection		Up to Week 53
Secondary	Percentage of Participants who Experience Major Bacterial Infections		Up to Week 53
Secondary	Rate of all Bacterial Infections Determined by the Investigator		Up to Week 53
Secondary	Time to First Onset of Non-Major Bacterial Infections		Up to Week 53
Secondary	Percentage of Participants who Experience Bacterial Infections		Up to Week 53
Secondary	Number of Days on Which Participants Were on Antibiotics		Up to Week 53
Secondary	Number of Hospitalizations due to any Infections		Up to Week 53
Secondary	Duration of Hospitalizations due to any Infections		Up to Week 53
Secondary	Number of Hospitalizations due to Major Bacterial Infections		Up to Week 53
Secondary	Duration of Hospitalizations due to Major Bacterial Infections		Up to Week 53
Secondary	Rate of all Infections as Determined by the Investigator		Up to Week 53
Secondary	Number of Participants with Validated Infections		Up to Week 53
Secondary	Time to First Onset of any Infection		Up to Week 53