Clinical trial NCT06181786: Study of NAV-240 in Healthy Volunteers
Official title: A Randomized, Double-Blind, Placebo-controlled, Single and Multiple Ascending Dose Phase 1 Clinical Study to Evaluate Safety, Tolerability, and Pharmacokinetics of NAV-240 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Pharmacokinetics
IMB-101
OX40L/TNF bispecific antibody
NAV-240
Lead sponsor: Navigator Medicines, Inc.
Sponsor class: INDUSTRY
Collaborators: name: IMBiologics Corp.
First posted: 2023-12-26
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The primary purpose of this study is to evaluate the safety and tolerability of intravenous (IV) doses of NAV-240 in healthy volunteers.


Eligibility criteria: Key Inclusion Criteria:

1. The participant is 18 to 55 years of age, inclusive, at screening.
2. The participant has a BMI of 18.5 to ≤ 32 kg/m\^2 at screening.
3. The participant is considered by the investigator to be in good general health as determined by medical history, clinical laboratory test results, vital sign measurements, 12-lead ECG results, and physical examination findings not clinically significant at screening.
4. Female participants of childbearing potential must use at least 1 form of highly effective methods of birth control from screening until at least 90 days after last study drug dose; OR be surgically sterile OR be postmenopausal. All female participants of childbearing potential must have a negative pregnancy test at screening and before the first dose of study drug. Female participants must also agree to refrain from egg donation during the study and for at least 90 days after study drug dosing.
5. Male participants must agree to use a condom when sexually active with a female partner of childbearing potential during the study and for at least 90 days after study drug dosing (OR be surgically sterile; OR agree to practice abstinence during the study and for at least 90 days after study drug dosing).
6. The participant agrees to comply with all protocol requirements.
7. The participant is able to provide written informed consent.

Key Exclusion Criteria:

1. The participant has any significant acute or chronic medical illness that, in the opinion of the investigator, would impact the participant's ability to complete all study requirements or that might impact the assessment of study data; or the participant has had a clinically significant illness within 30 days prior to study drug dosing per investigator discretion.
2. The participant has a positive COVID-19 molecular diagnostic test result at screening or prior to study drug dosing; or the participant has known or suspected current sequelae from a prior episode of COVID-19.
3. The participant has had major surgery, as determined by the investigator, within 12 weeks prior to study drug dosing.
4. The participant has any of the following prior to study drug dosing:

   • Systolic blood pressure \>140 mmHg and/or diastolic blood pressure \>90 mmHg.
5. The participant has any of the following on 12-lead ECG prior to study drug dosing, confirmed by repeat:

   * Heart rate \<40 or \>100 beats per minute.
   * PR interval \>220 milliseconds (ms).
   * QRS width \>120 ms.
   * QTcF \>=450 ms (male) or \>=470 ms (female).
6. The participant has any of the following clinical laboratory results at screening, confirmed by repeat:

   * WBCs, lymphocytes, or neutrophil counts outside site acceptable ranges per site SOPs.
   * eGFR \< 60 mL/min/1.73m\^2 (the CKD-EPI formula)
   * ALT or AST \>2\*ULN
   * Total bilirubin \>2\*ULN
7. The participant has a positive test result for HBsAg, anti-HBcAb, hepatitis C virus antibody, or HIV types 1 or 2 antibodies at screening.
8. The participant has a history of TB, active TB, or a positive Quantiferon-TB Gold Plus (QFT-Plus) test at screening.
9. The participant has received any vaccine or used any prescription or over the-counter medications (except acetaminophen \[up to 2 g per day\]), including herbal or nutritional supplements, within 14 days prior to study drug dosing.
10. The participant has received biologic agents within the 3 months prior to study drug dosing, or 5 half-lives, whichever is greater. Participants with a prior history of anti-TNFα exposure will be excluded.
11. The participant is a smoker or has regularly used nicotine or nicotine-containing products within 3 months prior to study drug dosing.
12. History of drug abuse within 1 year prior to screening.
13. The participant has a positive test result for drugs of abuse, alcohol, or cotinine (indicating active current smoking) at screening or prior to study drug dosing.
14. The participant has donated blood or blood products \>500 mL within 30 days prior to study drug dosing.
15. The participant has a history of hypersensitivity to vaccines, the study drug, or to drugs of similar chemical classes including allergy to drug or its excipients.
16. Any reason which, in the opinion of the Investigator, would prevent the participant from participating in the study.

Primary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From the dose of study drug on Day 1 up to Day 71
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Time to Maximum Serum Concentration (Tmax) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Area Under the Serum Concentration-Time Curve From Time Zero to 336 hours post-dose (AUC0-336) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Area Under the Serum Concentration-Time Curve from Time Zero to the Concentration at a given Time Point (AUC0-t) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Area Under the Serum Concentration-Time Curve from Time Zero to Infinity (AUC0-inf) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Serum Elimination Half-life (t1/2) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Terminal Elimination Rate Constant (λz) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Apparent Total Body Clearance (CL) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Apparent Volume of Distribution (Vz) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Trough Serum Concentration (Ctrough) of NAV-240
timeFrame: From Day 1 prior to the first dose of study drug up to Day 71
measure: Incidence of Presence of Antidrug Antibodies (ADAs)
timeFrame: From the first dose of study drug up to Day 71
measure: ADA Titers in Participants with Positive ADA
timeFrame: From the first dose of study drug up to Day 71
Other outcomes:
Locations:
city: Miami
country: United States
facility: Syneos Health
state: Florida
Study officials:
affiliation: Navigator Medicines, Inc.
name: Dana McClintock, MD
role: STUDY_DIRECTOR
References: