Clinical trial NCT06674941: A Trial to Investigate Teprotumumab (High-concentration Formulation) Subcutaneous Administration in Healthy Adult Non-Japanese and Japanese Participants
Official title: A Phase 1, Open-label, Single-dose Trial to Evaluate the Pharmacokinetics, Safety and Tolerability of Teprotumumab (High-concentration Formulation) Subcutaneous Administration in Healthy Adult Non-Japanese and Japanese Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Thyroid eye disease
Graves' ophthalmopathy
Graves' orbitopathy
Thyroid-associated ophthalmopathy
Immunology
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-11-05
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The primary objective of this trial are to assess the pharmacokinetics (PK) of a single subcutaneous (SC) administration of teprotumumab high-concentration formula (HCF) in healthy adult non-Japanese and Japanese participants and to assess the PK of teprotumumab delivered by syringe pump and by an injection device in non-Japanese participants.


Eligibility criteria: Inclusion Criteria:

1. Participant is a healthy male or female between the ages of 18 and 55 years, inclusive, at Screening.
2. Participant has a body mass index between 18 and 30 kg/m\^2, inclusive, at Screening.
3. Participant is medically healthy, with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or 12-lead ECG results at Screening, as deemed by the Principal Investigator (PI) or designee.
4. If female of childbearing potential (including those with an onset of menopause \< 2 years prior to Screening, non-therapy-induced amenorrhea for \< 12 months prior to Screening or not surgically sterile \[absence of ovaries and/or uterus\]) must have a negative serum pregnancy test at Screening and Check-in and negative urine pregnancy tests at all protocol-specified time points (ie, prior to the teprotumumab dose and throughout participation in the Follow-up Period); female participants of childbearing potential who are sexually active with a non-vasectomized male partner must agree to use 2 reliable forms of contraception during the trial, 1 of which is recommended to be hormonal, such as an oral contraceptive. Hormonal contraception must be started at least 1 full cycle prior to Day 1 and continue for 180 days after receiving the dose of teprotumumab. Highly effective contraceptive methods (with a failure rate \< 1% per year), when used consistently and correctly, include implants, injectables, combined oral contraceptives, some intrauterine devices, vasectomized partner, or sexual abstinence. Abstinence should only be used as a contraceptive method if it is in line with the participant usual and preferred lifestyle. Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) is not an acceptable method of contraception.
5. If female, participant must agree not to donate an egg/oocyte from Day 1 until 180 days after receiving the dose of teprotumumab.
6. If male, participant must be surgically sterile for at least 6 months prior to dosing or, if sexually active with a female partner of childbearing potential, must agree to use a barrier contraceptive method from Screening through 180 days after receiving the dose of teprotumumab.
7. If male, must agree not to donate sperm from Day 1 until 180 days after receiving the dose of teprotumumab.
8. Participant has adequate venous access.
9. Participant understands the trial procedures in the ICF and is willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial.

   Additional Inclusion Criteria for Cohort 2:
10. First generation Japanese healthy male or female participants must meet all of the following as confirmed by interview:

    1. Descendants of 4 ethnic Japanese grandparents who were born in Japan
    2. Both parents are ethnic Japanese who were born in Japan
    3. Hold a Japanese passport or identity papers
    4. Have lived outside Japan for less than 10 years at the time of screening and lifestyle including diet has not changed significantly since leaving Japan.

Exclusion Criteria:

1. Participant has a history or presence of a clinically significant medical or psychiatric condition or disease, in the opinion of the PI or designee.
2. Participant has a history of any illness that, in the opinion of the PI or designee, might confound the results of the trial or pose an additional risk to the participant due to participation in the trial.
3. Participant has a history or presence of alcoholism (defined as \> 10 standard drinks per week, where 1 standard drink = 284 mL of full-strength \[4.9% alc/vol\] beer, 30 mL of 40% \[alc/vol\] spirit or a 100 mL glass of wine\]) or drug abuse within the 6 months prior to Day 1 dosing.
4. Participant has a history or presence of hypersensitivity or idiosyncratic reaction to components of teprotumumab or prior hypersensitivity reactions to a monoclonal antibody or history.
5. Participant has a history or presence of:

   1. thyroid eye disease
   2. diagnosis of autoimmune diseases
   3. inflammatory bowel disease
6. Participant has an alanine transaminase or aspartate transaminase level \> 1.5 times upper limit of normal at Screening or Check-in.
7. Participant has glycated hemoglobin ≥ 6.5% and/or fasting glucose level (after at least an 8-hour fast) \> 126 mg/dL at Screening.
8. Participant has clinically significant abnormal ECG measurements at Screening or prior to teprotumumab dosing, in the opinion of the PI, or has second- or third-degree atrioventricular block or any of the following:

   1. QRS \> 120 msec
   2. QTcF) \> 450 msec (males) or \> 470 msec (females)
   3. PR interval \> 220 msec
9. Participant has a medical condition associated with increased risk of bleeding, including history of hematological diseases such as acquired platelet disorders and coagulation disorders, including drug-induced thrombocytopenia, idiopathic thrombocytopenia or von t medication.
10. Participant has donated blood, has had significant blood loss, or has received a transfusion of any blood or blood products within 60 days prior to Day 1 or plasma donation within 7 days prior to Day 1.
11. Participant has participated in another clinical trial within 30 days (or 5 half-lives of the trial drug, whichever is longer) prior to Day 1. The 30-day (or 5 half-lives) window will be derived from the date of last dosing in the previous trial to the date of Day 1 of the current trial.
12. Participant has previous participation in a teprotumumab clinical trial or received teprotumumab or any anti-human insulin-like growth factor-1 receptor monoclonal antibody.
13. Participant has any other condition that, in the opinion of the Investigator, would preclude inclusion in the trial.
14. Participant has used any prescription (excluding hormonal birth control) or over-the-counter medications, including herbal or nutritional supplements, within 14 days before receiving the study drug. Over-the-counter use of acetaminophen (up to 2 g per day), topical eye drops, and topical creams are allowed. Use of other over-the-counter medications may be allowed at the discretion of Investigator with approval from the Medical Monitor.

Primary outcomes:
measure: Area Under the Serum Concentration-time Curve (AUC) From Time 0 Extrapolated to Infinity (AUCinf) of Teprotumumab
timeFrame: Day 1 pre-dose to Day 57
measure: AUC From Time 0 to the Last Quantifiable Concentration (AUClast) of Teprotumumab
timeFrame: Day 1 pre-dose to Day 57
measure: Maximum Observed Serum Concentration (Cmax) of Teprotumumab
timeFrame: Day 1 pre-dose to Day 57
measure: Time to Cmax (Tmax) of Teprotumumab
timeFrame: Day 1 pre-dose to Day 57
Secondary outcomes:
measure: Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to Day 57
measure: Number of Participants with Anti-drug Antibodies (ADA) to Teprotumumab
timeFrame: Day 1 pre-dose to Day 57
measure: Titer of Positive ADA to Teprotumumab
timeFrame: Day 1 pre-dose to Day 57
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: PPD Development, LP
state: Nevada
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: