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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

Primary Purpose

Hypogammaglobulinemia, Bacterial Infections, B-cell Chronic Lymphocytic Leukemia

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Xembify
Placebo
Sponsored by
Grifols Therapeutics LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogammaglobulinemia focused on measuring XEMBIFY, CLL, SMT, Hypogammaglobulinemia (HGG)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • JD Medical Group LLCRecruiting
  • Optimed Research, LLCRecruiting
  • Allergy and Clinical Immunology AssociatesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

XEMBIFY + Standard Medical Treatment (SMT)

Placebo + SMT

Arm 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 weekly infusions of 150 mg/kg starting Week 2 (Day 8) through Week 53 (end of Treatment Phase). The SMT will include the antileukemic treatments and the other supportive treatments that the participants will need during their participation.

Participants will receive sterile 0.9 percent Sodium Chloride Injection, United States Pharmacopeia (USP) or equivalent starting at Week 1 (Days 1 to 5) SC for 5 consecutive daily doses followed by weekly infusions starting at Week 2 (Day 8) through Week 53. The SMT will include the antileukemic treatments and the other supportive treatments that the participants will need during their participation.

Outcomes

Primary Outcome Measures

Annual Rate of Major Bacterial Infections per Year

Secondary Outcome Measures

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

Full Information

First Posted
December 1, 2022
Last Updated
June 12, 2023
Sponsor
Grifols Therapeutics LLC
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1. Study Identification

Unique Protocol Identification Number
NCT05645107
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 26, 2022 (Actual)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
June 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grifols Therapeutics LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogammaglobulinemia, Bacterial Infections, B-cell Chronic Lymphocytic Leukemia
Keywords
XEMBIFY, CLL, SMT, Hypogammaglobulinemia (HGG)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
386 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
XEMBIFY + Standard Medical Treatment (SMT)
Arm Type
Experimental
Arm 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 weekly infusions of 150 mg/kg starting Week 2 (Day 8) through Week 53 (end of Treatment Phase). The SMT will include the antileukemic treatments and the other supportive treatments that the participants will need during their participation.
Arm Title
Placebo + SMT
Arm Type
Placebo Comparator
Arm Description
Participants will receive sterile 0.9 percent Sodium Chloride Injection, United States Pharmacopeia (USP) or equivalent starting at Week 1 (Days 1 to 5) SC for 5 consecutive daily doses followed by weekly infusions starting at Week 2 (Day 8) through Week 53. The SMT will include the antileukemic treatments and the other supportive treatments that the participants will need during their participation.
Intervention Type
Drug
Intervention Name(s)
Xembify
Other Intervention Name(s)
Immune Globulin Subcutaneous (Human), 20% (IGSC 20%)
Intervention Description
SC infusion pump
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
0.9% Normal Saline
Intervention Description
SC infusion pump
Primary Outcome Measure Information:
Title
Annual Rate of Major Bacterial Infections per Year
Time Frame
Up to Week 53
Secondary Outcome Measure Information:
Title
Time to First Onset of Major Bacterial Infection
Time Frame
Up to Week 53
Title
Percentage of Participants who Experience Major Bacterial Infections
Time Frame
Up to Week 53
Title
Rate of all Bacterial Infections Determined by the Investigator
Time Frame
Up to Week 53
Title
Time to First Onset of Non-Major Bacterial Infections
Time Frame
Up to Week 53
Title
Percentage of Participants who Experience Bacterial Infections
Time Frame
Up to Week 53
Title
Number of Days on Which Participants Were on Antibiotics
Time Frame
Up to Week 53
Title
Number of Hospitalizations due to any Infections
Time Frame
Up to Week 53
Title
Duration of Hospitalizations due to any Infections
Time Frame
Up to Week 53
Title
Number of Hospitalizations due to Major Bacterial Infections
Time Frame
Up to Week 53
Title
Duration of Hospitalizations due to Major Bacterial Infections
Time Frame
Up to Week 53
Title
Rate of all Infections as Determined by the Investigator
Time Frame
Up to Week 53
Title
Number of Participants with Validated Infections
Time Frame
Up to Week 53
Title
Time to First Onset of any Infection
Time Frame
Up to Week 53

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ailbhe de Bhulbh
Phone
0871103119
Ext
+353
Email
Ailbhe.debhulbh@grifols.com
First Name & Middle Initial & Last Name or Official Title & Degree
Terra Stockwell
Email
terra.stockwell@grifols.com
Facility Information:
Facility Name
JD Medical Group LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33176
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Felipe Gascon-Radon, Dr
Phone
786-420-2392
Email
fgascon-rodon@jdmedicalgroup.com
First Name & Middle Initial & Last Name & Degree
Silvia Hernandez
Phone
+1 614-505-1946
Email
shernandez@jdmedicalgroup.com
Facility Name
Optimed Research, LLC
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43235
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Donald McNeil, Dr.
Email
Damea@optimed.us.com
Facility Name
Allergy and Clinical Immunology Associates
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15241
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Palumbo, Dr.
Email
shidel.sue@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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