Clinical trial NCT06563856: A Study of TEPEZZA Subcutaneous Administration in Healthy Adults
Official title: A Phase 1, Open-Label, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TEPEZZA Subcutaneous Administration in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Bioavailability
Bioequivalence
Keywords: Thyroid eye disease
Graves' ophthalmopathy
Graves' orbitopathy
Thyroid-associated ophthalmopathy
Immunology
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-08-21
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of this study is to assess the pharmacokinetics (PK) parameters of a single subcutaneous (SubQ) infusion of TEPEZZA with and without ENHANZE™ Drug Product (EDP) at 2 dose levels in healthy adult participants.


Eligibility criteria: Inclusion Criteria:

* The participant is able to provide written informed consent.
* The participant is male or female 18 to 55 years of age, inclusive.
* The participant has a body mass index (BMI) between 21 to 30 kg/m\^², inclusive, and a minimum weight of 55 kg at Screening.
* The participant is considered by the investigator or designee to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead electrocardiogram (ECG) results, and physical examination findings at Screening.
* The participant has adequate venous access and can receive IV therapy.
* Female participants of childbearing potential must have a negative serum pregnancy test at Screening and Check-in and negative urine pregnancy tests at all other protocol-specified time points. Participants who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the study, one of which is recommended to be hormonal, such as an oral contraceptive.
* Female participants must agree not to donate an egg/oocyte from Day 1 until 180 days after receiving the study drug.

Male participants must agree not to donate sperm from Day 1 until 180 days after receiving the study drug.

-The participant is willing and able to comply with all protocol requirements and evaluations for the duration of the study.

Exclusion Criteria:

* The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) types 1 or 2 antibodies at Screening.
* The participant has a diagnosis of an autoimmune disease; or a history of HIV, hepatitis B virus (HBV), or HCV infection; a history of inflammatory bowel disease (IBD), or a history of or active thyroid eye disease (TED) at Screening.
* The participant has active liver disease or hepatic dysfunction at Screening or Check-in, as determined by alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels \>1.5 times upper limit of normal (ULN).
* The participant has glycated hemoglobin (HbA1c) levels ≥8% and/or fasting glucose levels (after at least an 8-hour fast) \>126 mg/dL (\>7 mmol/L) at Screening.
* The participant has a seated resting blood pressure of \<90/40 mmHg or \>140/90 mmHg, or a seated pulse rate of \<40 beats per minute (bpm) or \>99 bpm or is considered clinically significant at Screening. One additional measurement can be taken if blood pressure and pulse rate are outside the specified limits.
* The participant has clinically significant 12-lead ECG abnormalities at Screening and Check-in or, in the opinion of the investigator, has a second- or third-degree atrioventricular (AV) block, or has any of the following:

QRS \>120 msec

QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 msec (males) or \>470 msec (females)

PR interval \>220 msec

* The participant has used any prescription (excluding hormonal birth control) or over-the-counter medications (except paracetamol \[up to 2 g per day\]), including herbal or nutritional supplements, within 14 days before receiving the study drug.
* The participant has a medical condition associated with an increased risk of bleeding - including a history of hematological diseases such as acquired platelet disorders; coagulation disorders - including drug-induced thrombocytopenia, idiopathic thrombocytopenia, or von Willebrand's Disease; or requires the use of antiplatelet or anticoagulant medication.
* Female participants who are lactating or planning to become pregnant from Screening through 180 days after receiving the study drug.
* Male participants who are planning to impregnate a female partner from Day 1 through 180 days after receiving the study drug.
* The participant has consumed alcohol-, caffeine-, or xanthine-containing products within 48 hours before the dose of study drug.
* The participant is a smoker or has used nicotine or nicotine-containing products (e.g., snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) within 3 months before receiving the study drug.
* The participant has a history of alcohol abuse or drug addiction within the past 6 months prior to Day 1 dosing.
* The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at Screening or before receiving the study drug.
* The participant is involved in strenuous activity or contact sports within 24 hours before receiving the study drug and during the study.
* The participant has donated blood, had significant blood loss, or received a transfusion of any blood or blood products within 60 days prior to Day 1 dosing or received a plasma donation within 7 days prior to Day 1 dosing.
* The participant has a history of relevant drug and/or food allergies (i.e., allergy or idiosyncratic reaction to components of TEPEZZA or excipients; prior hypersensitivity reactions to mAbs, EDP, or excipients; or any significant food allergy that could preclude a standard diet in the clinical unit).
* The participant participated in another investigational study within 30 days (or 5 half-lives of the study drug, whichever is longer) prior to dosing on Day 1. The 30-day window will be derived from the date of the last blood collection or dosing, whichever is later, in the previous study to the date of Day 1 of the current study.
* The participant has previously participated in a TEPEZZA investigational study or has received TEPEZZA or rHuPH20-containing products.
* The participant has received a COVID-19 vaccination within 6 weeks before receiving the study drug or during the study.
* The participant has a positive test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Note: Testing will be performed according to site procedures.
* The participant is mentally or legally incapacitated or has significant emotional problems at Screening or is expected to have them during the conduct of the study.
* The participant has a history or presence of a clinically significant medical or psychiatric condition or disease in the opinion of the investigator or designee.
* The participant had a history of any illness that, in the opinion of the investigator or designee, might confound the results of the study or pose an additional risk to the participant by participation in the study.
* In the opinion of the investigator or designee, the participant is not suitable for entry into the study.

Primary outcomes:
measure: Cohort 1, 2, and 4: Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUCinf) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: AUC From Time 0 to the Last Quantifiable Concentration (AUClast) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Percentage of the Area Extrapolated for Calculation of AUCinf (%AUCextrap) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Maximum Observed Serum Concentration (Cmax) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Last Quantifiable Serum Concentration (Clast) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Time to Maximum Observed Serum Concentration (Tmax) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Time of Last Quantifiable Serum Concentration (Tlast) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Apparent Terminal Elimination Rate Constant (λz) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Apparent Terminal Half-life (t1/2) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Apparent Serum Clearance (CL/F) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 1, 2, and 4: Apparent Volume of Distribution During the Terminal Phase (Vz/F) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
Secondary outcomes:
measure: Cohort 3: AUCinf of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: AUClast of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: %AUCextrap of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: Cmax of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: Clast of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: Tlast of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: λz of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: t1/2 of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: Total Serum Clearance (CL) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: Estimated Volume of Distribution at Steady State (Vss) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Cohort 3: Volume of Distribution During the Terminal Phase (Vz) of TEPEZZA
timeFrame: Day 1 pre-dose to Day 71
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to approximately Day 71
measure: Number of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to approximately Day 71
measure: Number of Participants with Detectable Anti-drug Antibodies (ADA) to TAPEZZA
timeFrame: Day 1 pre-dose to Day 71
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: PPD Development
state: Nevada
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: