Clinical trial NCT04578535: A Study to Assess the Tolerability, Safety, and Pharmacokinetics of Subcutaneous Immune Globulin Infusion 10% (Human) With Recombinant Human Hyaluronidase (HYQVIA/HyQvia) With Ramp-up and No Ramp-up Dosing in Healthy Adult Participants
Official title: A Phase 1, Open-Label, Randomized Study to Assess the Tolerability, Safety, and Pharmacokinetics of Subcutaneous Immune Globulin Infusion 10% (Human) With Recombinant Human Hyaluronidase (HYQVIA/HyQvia) With Ramp-Up and No Ramp-Up Dosing in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Takeda
Sponsor class: INDUSTRY
Collaborators: name: Baxalta Innovations GmbH, now part of Shire
First posted: 2020-10-08
Enrollment: 51
Sex: ALL
Minimum age (years): 19
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to assess the tolerability, safety, and pharmacokinetics of HYQVIA with ramp-up and no ramp-up dosing in healthy adult participants.

Detailed description: This study will comprise of Part 1 and Part 2. Each study part will consist of three treatment arms (Part 1 \[approximately 24 participants\]: Treatment Arms 1-3 and Part 2 \[approximately 24 participants\]: Treatment Arms 4-6). Treatment arms will be initiated in parallel within each study part. Each participant will participate in only one treatment arm. After participants in Treatment Arms 1-3 (Study Part 1) will complete Week 9, the tolerability and, safety data through Week 9 will be reviewed by a safety review team. (Participants in arms 1-3 will continue in the study as the safety review is being completed.) Once the safety review for Arms 1-3 (Study part 1) will be completed and approved, Treatment Arms 4-6 (Study Part 2) will begin.

Eligibility criteria: Inclusion Criteria:

* An understanding, ability, and willingness to fully comply with study procedures and restrictions
* Ability to voluntarily provide written, signed, and dated (personally or via a legally authorized representative) informed consent to participate in the study
* Age 19-50 years inclusive at the time of consent. The date of signature of the informed consent is defined as the beginning of the screening period. This inclusion criterion will only be assessed at the first screening visit
* Male, or non-pregnant, non-breastfeeding female who agrees to comply with any applicable contraceptive requirements of the protocol, or females of non-childbearing potential
* Must be considered "healthy". Healthy as determined by the investigator on the basis of screening evaluations and healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead electro cardiogram (ECG), hematology, blood chemistry, and urinalysis
* Body mass index (BMI) between 18.0 and 30.0 kilogram per square meter (kg/m\^2) inclusive

Exclusion Criteria:

* Any current or relevant history of medical (e.g. any hematological, hepatic, respiratory, cardiovascular, renal or neurological) or psychiatric conditions, which by judgment of the investigator might compromise the safety of the participant or integrity of the study, interfere with the participant's participations in the trial and compromise the trial objectives or any condition that presents undue risk from the investigational product or procedures Note: Participants on stable dose of hormone replacements (i.e. thyroid hormone replacement) or oral contraceptives are permitted
* Clinically significant cardiac conditions including but not limited to uncontrolled hypertension, myocardial infarction, unstable coronary artery disease and clinically significant arrhythmias and conduction disorders
* Known or suspected intolerance or hypersensitivity to the investigational product(s), closely related compounds, or any of the stated ingredients (e.g. human IG, hyaluronidase, albumin)
* Known history of hypersensitivity or severe allergic reactions (e.g. urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following administration of blood or blood components
* Significant illness, as judged by the investigator, within 30 days of the first dose of investigational product
* Known history of alcohol or other substance abuse within the last year
* Donation of blood within 60 days, or blood products (e.g., plasma or platelets) within 2 weeks prior receiving the first dose of investigational product
* Participants will be excluded if any of the following laboratory parameters meet the criteria below:
* Hemoglobin less than (\<) 11 gram per deciliter (g/dL). Absolute neutrophil count less than or equal to (\< or =) 1500/ cubic millimeter (mm\^3) and platelet count less than or equal to (\< or =) 100,000/mm\^3 Liver function: alanine aminotransferase (ALT) greater than or equal to \> or =2.5 × upper limit normal (ULN), aspartate aminotransferase (AST) \> or =2.5 × upper limit normal (ULN), alkaline phosphatase \> or =1.5 × ULN or total bilirubin \> or =1.5 milligram per deciliter (mg/dL) Renal function: creatinine clearance \<or= 60 milliliter per minute (mL/min) based on Cockcroft-Gault equation Coagulation tests: activated partial thromboplastin time (aPTT) \>1.2 X ULN; international normalized ratio (INR) \>1.2 Participants will be excluded if any other laboratory values are outside the reference range and are clinically significant per investigator's judgment.
* Within 30 days prior to the first dose of investigational product:

  * Has participated in another clinical study involving immunoglobulin products within 12 months of screening.
  * Have used an investigational product (or 5 half-lives, whichever is longer).
  * Have been enrolled in a clinical study (including vaccine studies or has been vaccinated with approved product) that, in the investigator's opinion, may impact this study. Participants who have received any vaccine (including live attenuated vaccines) during the last 30 days before dosing will be excluded. No live attenuated virus vaccines are allowed during the study until the end of the follow up period
  * Have had any substantial changes in eating habits, as assessed by the investigator.
* Confirmed systolic blood pressure \>139 mmHg or \<89 mmHg and diastolic blood pressure \>89 mmHg or \<49 millimeters of Mercury (mmHg)
* A positive screen for alcohol or drugs of abuse at screening or D-1
* A positive human immunodeficiency virus (HIV), hepatitis C virus (HCV), or ongoing/active hepatitis B infection at screening. Participants with immunity to hepatitis B from either active vaccination or from previous natural infection are eligible to participate in the study.
* Smoking more than 5 cigarettes or equivalent per day, unable to stop smoking during confinement in the CRU
* Severe dermatitis or anatomical abnormality that would interfere with HYQVIA administration or endpoint assessments Note: the skin at the administration site should not be covered by tattoos.
* Current use of any herbal, or homeopathic preparations are not permitted
* Unable or unwilling to discontinue antihistamines or medications with antihistamine properties, sedatives, anxiolytics, systemic steroids, or topical steroids or antibiotics on any area below the chest for a minimum of 48 hours prior to each infusion visit and through 72 hours post last infusion
* Current or relevant history of hypercoagulable conditions (e.g. Protein C, Protein S, and antithrombin III deficiency), thrombotic/thromboembolic events or venous thrombosis

Primary outcomes:
measure: Number of Participants Who Tolerated All Initiated HYQVIA Infusion
timeFrame: From start of the study drug administration up to Week 9
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of the study drug administration up to Week 25
measure: Number of Participants Who Developed Binding and Neutralizing Antibodies to Recombinant Human Hyaluronidase PH20 (rHuPH20)
timeFrame: From start of the study drug administration up to Week 25
measure: Time of Maximum Observed Serum Concentration (Tmax) of Total IgG and IgG Subclasses (IgG1, IgG2, IgG3, IgG4)
timeFrame: Pre-dose (Day 1), and 48, 96, 144 and 192 hours post-dose for all treatment arms; 360 hours post-dose for treatment arms 2 and 5; 360 and 696 hours post-dose for treatment arms 3 and 6
measure: Maximum Observed Serum Concentration (Cmax) Sampled During a Dosing Interval of Total IgG and IgG Subclasses (IgG1, IgG2, IgG3, IgG4)
timeFrame: Pre-dose (Day 1), and 48, 96, 144 and 192 hours post-dose for all treatment arms; 360 hours post-dose for treatment arms 2 and 5; 360 and 696 hours post-dose for treatment arms 3 and 6
measure: Area Under the Curve From the Time of Dosing to the Last Time Point With Measurable Concentration (AUClast) of Total IgG and IgG Subclasses (IgG1, IgG2, IgG3, IgG4)
timeFrame: Pre-dose (Day 1), and 48, 96, 144 and 192 hours post-dose for all treatment arms; 360 hours post-dose for treatment arms 2 and 5; 360 and 696 hours post-dose for treatment arms 3 and 6
measure: Terminal Half-Life (T1/2) of Total IgG and IgG Subclasses (IgG1, IgG2, IgG3, IgG4)
timeFrame: Pre-dose (Day 1), and 48, 96, 144 and 192 hours post-dose for all treatment arms; 360 hours post-dose for treatment arms 2 and 5; 360 and 696 hours post-dose for treatment arms 3 and 6
measure: Apparent Total Clearance After Extravascular Administration (CL/F) of Total IgG and IgG Subclasses (IgG1, IgG2, IgG3, IgG4)
timeFrame: Pre-dose (Day 1), and 48, 96, 144 and 192 hours post-dose for all treatment arms; 360 hours post-dose for treatment arms 2 and 5; 360 and 696 hours post-dose for treatment arms 3 and 6
measure: Apparent Volume of Distribution Associated With the Terminal Slope Following Extravascular Administration (Vz/F) of Total IgG and IgG Subclasses (IgG1, IgG2, IgG3, IgG4)
timeFrame: Pre-dose (Day 1), and 48, 96, 144 and 192 hours post-dose for all treatment arms; 360 hours post-dose for treatment arms 2 and 5; 360 and 696 hours post-dose for treatment arms 3 and 6
Other outcomes:
Locations:
city: Hialeah
country: United States
facility: Clinical Pharmacology of Miami, Inc
state: Florida
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: