Study to Investigate the Effect of BL-8040 (Motixafortide) on the QTc Interval in Healthy Subjects

NCT05293171 | Completed Phase 1 Results FDA Drug

• 1 other identifier: BL-8040.TQT.103
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the corrected QT (QTc) effects (electrocardiogram \[ECG\]) of motixafortide (BL-8040) 1.25 mg/kg (therapeutic dose) and 2 mg/kg (supratherapeutic dose) following a single subcutaneous (SC) injection relative to placebo in approximately 40 healthy subjects.

Conditions

Healthy Subjects

Outcome Measures

Primary Outcomes (1)

• QTc Effect of Single Subcutaneous (SC) Injections of Motixafortide (BL-8040) 1.25 mg/kg and 2 mg/kg

  Assessment of the QTc effects of motixafortide 1.25 mg/kg and 2 mg/kg following a single SC injection relative to placebo in healthy subjects by evaluation of the relationship between the plasma concentration of motixafortide and ΔΔQTcI (change from baseline in QTcI)

  Cardiodynamic ECG recordings on Day 1 (day of dosing) at different time points prior to dosing and up to 24 hours post-dose in each period (each period is 24 hours long, a total of 4 periods)

Secondary Outcomes (6)

• Evaluation of AEs, 12-lead Safety ECGs, Vital Signs, Clinical Laboratory Tests, and Physical Examinations.

  During the entire study. For each participant starting from Screening until End of Study Visit - approximately 1 month.

• PK (AUC0-t and AUC0-inf) of Single Therapeutic and Supratherapeutic SC Injections of Motixafortide (BL-8040) in Healthy Subjects.

  Blood for motixafortide PK is collected prior to dosing and at 13 different timepoints following dosing up to 24 hours

• PK (AUC%Extrap) of Single Therapeutic and Supratherapeutic SC Injections of Motixafortide (BL-8040) in Healthy Subjects.

  Blood for motixafortide PK is collected prior to dosing and at 13 different timepoints following dosing up to 24 hours

• PK (Cmax) of Single Therapeutic and Supratherapeutic SC Injections of Motixafortide (BL-8040) in Healthy Subjects.

  Blood for motixafortide PK is collected prior to dosing and at 13 different timepoints following dosing up to 24 hours

• PK (Tmax) of Single Therapeutic and Supratherapeutic SC Injections of Motixafortide (BL-8040) in Healthy Subjects.

  Blood for motixafortide PK is collected prior to dosing and at 13 different time points following dosing up to 24 hours

Study Arms (4)

1.25 mg/kg BL-8040 + BL-8040-matching placebo administered via SC injection (Therapeutic)

EXPERIMENTAL

1.25 mg/kg BL-8040 + BL-8040-matching placebo administered via SC injection (Therapeutic)

Drug: 1.25 mg/kg BL-8040 + BL-8040-matching placebo

2 mg/kg BL-8040 administered via SC injection (Supratherapeutic)

EXPERIMENTAL

2 mg/kg BL-8040 administered via SC injection (Supratherapeutic)

Drug: 2 mg/kg BL-8040

BL-8040-matching placebo administered via SC injection

PLACEBO COMPARATOR

BL-8040-matching placebo administered via SC injection

Drug: BL-8040-matching placebo

400 mg moxifloxacin (1 x 400 mg tablet) administered orally

ACTIVE COMPARATOR

400 mg moxifloxacin (1 x 400 mg tablet) administered orally

Drug: 400 mg Moxifloxacin (1x400 mg tablet)

Interventions

1.25 mg/kg BL-8040 + BL-8040-matching placebo DRUG

Administered via subcutaneous (SC) injection

1.25 mg/kg BL-8040 + BL-8040-matching placebo administered via SC injection (Therapeutic)

2 mg/kg BL-8040 DRUG

Administered via subcutaneous (SC) injection

2 mg/kg BL-8040 administered via SC injection (Supratherapeutic)

BL-8040-matching placebo DRUG

Administered subcutaneous (SC) injection

BL-8040-matching placebo administered via SC injection

400 mg Moxifloxacin (1x400 mg tablet) DRUG

Administered orally

400 mg moxifloxacin (1 x 400 mg tablet) administered orally

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, adult, males and females between the ages of 18 and 55 years, inclusive, at Screening.
• Body weight between 50-109 kg (inclusive) and body mass index (BMI) within 18.0-29.99 kg/m2 (inclusive) at Screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs or ECGs, as deemed by the PI or designee.
• Current non-smokers who have not used any nicotine-containing products (chewed or smoked) or replacement products including electronic cigarettes for at least 3 months prior to first dosing.
• Women must meet one of the following criteria: a) postmenopausal; b) surgically sterile; c) of childbearing potential and practicing contraception, as described below:
• Postmenopausal (postmenopausal women must have no menstrual bleeding for at least 1 year prior to first dosing and menopause is confirmed by follicle-stimulating (FSH) levels consistent with postmenopausal status), or
• Surgically sterile (e.g., hysterectomy, bilateral oophorectomy, hysteroscopic sterilization) for at least 6 months prior to first dosing, or
• Women of childbearing potential must be non-lactating and agree to either using a highly effective acceptable form of birth control (e.g., non-hormonal intrauterine device plus condom and spermicide).
• A non-vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days after the last dosing. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to the first dosing. A male who has been vasectomized less than 4 months prior to study first dosing must follow the same restrictions as a non-vasectomized male.)
• If male, must agree not to donate sperm from the first dosing until 90 days after the last dosing.
• Understands the study procedures in the informed consent form (ICF), and is willing and able to comply with the protocol.

You may not qualify if:

• Past or present diseases, which, as judged by the PI or designee, may affect the outcome of this study or pose an additional risk to the subject by their participation in the study, including, but not limited to, significant medical abnormality including: psychiatric, neurologic, pulmonary, cardiac, gastrointestinal, genitourinary, renal, metabolic, endocrinologic, or autoimmune disorder.
• Is mentally or legally incapacitated or has significant emotional problems at the time of the Screening visit or expected during the conduct of the study.
• Positive result for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody at Screening.
• Family history of QTc prolongation or of unexplainable sudden death at \<50 years of age.
• History or presence of any of the following:
• sick sinus syndrome, second or third degree atrioventricular block, myocardial infarction, pulmonary congestion, symptomatic or significant cardiac arrhythmia, prolonged Fridericia corrected QT (QTcF) interval, or conduction abnormalities;
• ischemic heart disease, symptomatic arrhythmias, or poorly controlled hypertension.
• Knowledge of any kind of cardiovascular disorder/condition known to increase the possibility of QT prolongation or history of additional risk factors for torsade de pointes (e.g., heart failure, clinically significant hypokalemia, family history of Long QT Syndrome or Brugada Syndrome) or cardiac conduction disorders.
• Any condition that may interfere with the absorption, metabolism, or elimination of the study drug.
• History of, or active, alcohol or illicit drug abuse as defined by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, manual, within 2 years prior to the first dosing. Alcohol abuse is defined as an average intake of two or more drinks (12 oz beer, 1.5 oz of hard liquor, or equivalent) per day.
• Laboratory safety test results that are outside of the normal reference ranges (unless clinically acceptable to the PI or designee) at Screening.
• Resting supine heart rate (HR) \<50 bpm or \>100 bpm at Screening or check-in (Day -2). Minor deviations will be acceptable if considered to be of no clinical significance by the PI or designee.
• Resting supine systolic blood pressure \<90 mmHg or \>140 mmHg; resting supine diastolic blood pressure \<50 mmHg or \>90 mmHg at Screening or check-in.
• Significant history or presence of ECG findings at Screening or check-in (Day -2), including:
• QTcF \>450 msec

Sponsors & Collaborators

• BioLineRx, Ltd.: lead
• Celerion: collaborator

Study Sites (1)

Celerion

Phoenix, Arizona, 85283, United States

Location

MeSH Terms

Interventions

4-fluorobenzoyl-TN-14003; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: VP Clinical & Medical Affairs
• Organization: BioLineRx Ltd

clinicaltrials@biolinerx.com

+972-8-6429100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a randomized, double-blind (in respect to BL-8040 and BL-8040-matching placebo dosing), placebo- and positive-controlled, 4-period, 4-way crossover study. On Day 1 of Period 1, subjects will be randomized to 1 of 12 treatment sequences. Each treatment sequence comprises 4 treatment periods. Each subject will be assigned a unique identification number upon screening. Subjects who complete the study screening assessments and meet all the eligibility criteria will be assigned a unique randomization identification number at the time of the first dosing, different from the screening number, and will receive the corresponding study drug, according to a randomization scheme. Subjects will receive each of the 4 Treatments in a pre-defined order according to the sequence scheme determined at randomization.

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: March 24, 2022
• Study Start: June 11, 2021
• Primary Completion: June 1, 2022
• Study Completion: August 15, 2022
• Last Updated: March 21, 2025
• Results First Posted: March 21, 2025

Record last verified: 2025-03

Locations

US (1)