Single or Repeat Dose of G03-52-01 in Adult Subjects
- Conditions
- HealthyBotulinum Toxin
- Interventions
- Drug: G03-52-01Drug: Placebo
- Registration Number
- NCT05348993
- Lead Sponsor
- Resilience Government Services, Inc.
- Brief Summary
A Phase 2, randomized, double-blind, placebo-controlled single or repeat dose trial
- Detailed Description
A Phase 2, multicenter, randomized, double-blinded, placebo-controlled study to evaluate a single (100 mg) or repeat dose (50 mg and 100 mg) of G03-52-01 administered by IM injection(s) in adult subjects. Approximately 625 subjects will be enrolled in this study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 625
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Informed consent understood and signed prior to screening procedures.
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Assessed by the Investigator to be a healthy male or healthy, non-pregnant, non-lactating female between the ages of 18 and 65 inclusive on the day of dosing.
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Able and willing to comply and be available for all protocol procedures and follow-up for the duration of the study.
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Body Mass Index (BMI) of ≥18.5 and ≤35 kg/m2.
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Females of child-bearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test on Day 1 prior to dosing.
- A woman is considered of childbearing potential unless post-menopausal (≥ 1 year without menses) or surgically sterilized via bilateral oophorectomy, or hysterectomy or bilateral tubal ligation.
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If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men or use medically effective contraception (methods with a failure rate of < 1% per year when used consistently and correctly) during participation in the study. Acceptable methods include:
- Hormonal contraception including implants, injections or oral
- Two barrier methods, e.g., condom and cervical cap (with spermicide) or diaphragm (with spermicide)
- Intrauterine device (IUD) or intrauterine system
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Screening clinical laboratory results within normal ranges or are no greater than a Grade 1 and deemed not clinically significant by Medical Monitor (MM) and Principal Investigator (PI). Any subjects with results that are Grade 2 or above according to Appendix B will be excluded.
- Laboratory values that are outside the range of eligibility but are thought to be due to an acute condition or due to laboratory error may be repeated once.
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The urine drug screen is negative.
- For Cohorts 1-3, if a subject has a positive urine drug screen that the PI believes is caused by a currently prescribed medication, (except for THC), the PI may enroll the subject if they meet all inclusion criteria, and none of the exclusion criteria.
- For Cohort 4, if a subject has a positive urine drug screen that the PI believes is caused by a currently prescribed medication or positive for THC, the PI may enroll the subject if they meet all other inclusion criteria and none of the exclusion criteria.
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Breathalyzer test is negative.
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Available for follow-up for the duration of the study.
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Agrees not to participate in vigorous activity 2 days prior to dosing and 2 days post-dose Day 1 and Day 45 for Cohorts 1-3 and Day 1 for Cohort 4, per Investigator discretion.
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History of a chronic medical condition that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject.
- Chronic medical conditions include but are not limited to diabetes; Asthma requiring use of medication in the year before screening; Autoimmune disorder such as lupus, Wegener's, rheumatoid arthritis, thyroid disease; coronary artery disease; chronic hypertension; History of malignancy except low-grade (squamous and basal cell) skin cancer thought to be cured; chronic renal, hepatic, pulmonary, or endocrine disease (except previous asthma which has required no treatment for the past year).
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Known history of severe allergic reaction of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobulins.
- Severe allergic reactions are defined as any of the following: anaphylaxis, urticaria, or angioedema.
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Known allergic reactions to any of the study product components present in the formulation or in the processing.
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A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds).
-
Clinically significant abnormal electrocardiogram (ECG) at screening.
- Clinically significant abnormal ECG results include but are not limited to: complete left or right bundle branch block; other ventricular conduction block except for incomplete RBB; 2nd degree or 3rd degree atrioventricular (AV) block; sustained ventricular arrhythmia; sustained atrial arrhythmia; two Premature Ventricular Contractions in a row; pattern of ST elevation felt consistent with cardiac ischemia; or any condition deemed clinically significant by a study investigator.
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Positive serology results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies.
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Febrile illness with temperature ≥38°C within 7 days of dosing. Subjects with acute febrile illness within 7 days of dosing may be rescreened no earlier than 7 days following resolution of symptoms.
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Female subjects that are pregnant or breastfeeding or intending to become pregnant within the projected duration of the trial starting from the Screening visit until last dose.
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Donation of blood or blood product within 56 days of enrollment.
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Is currently participating or has participated in a study with an investigational product (IP) within 28 days preceding Day 1 (documented receipt of placebo in a previous trial would be permissible for trial eligibility)
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Plans to enroll in another clinical trial that could interfere with safety assessment of the IP at any time during the study period.
- Includes trials that have a study intervention such as a drug, biologic, or device only
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Treatment with a mAB within 3 months of Day 1.
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Receipt of antibody (e.g., tetanus immune globulin [TIG], varicella zoster immune globulin [VZIG], intravenous immunoglobulin [IVIG], IM gamma globulin) or blood transfusion within 6 months or within 5 half-lives of the specific product given.
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Reported active drug or alcohol or substance abuse/independence or illicit drug use that, in the opinion of the Investigator, would interfere with adherence to study requirements.
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Use of H1 antihistamines or beta-blockers within 5 days of dosing Day 1 and Day 45 for Cohorts 1-3 and Day 1 for Cohort 4 (PRN use could be allowed with MM approval).
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Use of any prohibited medication within 28 days prior to study entry or planned use during the study period.
- Note: Prohibited medications include immunosuppressives (except nonsteroidal anti-inflammatory drugs [NSAIDs]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents.
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Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or previous treatment with equine antitoxin.
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Any previous injection or any planned injection within 4 months after enrollment of botulinum toxin for cosmetic reasons, spastic dysphonia, torticollis, or any other reason.
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Any illness or condition that in the judgment of the Investigator may affect the safety of the subject or the evaluation of any study endpoint.
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Is a study site employee, staff, or close relative as defined.
- PIs and Sub-Investigators
- Staff who are supervised by the PI, Sub-Investigators
- Member of the team conducting this clinical trial
- Children, spouse, partners, siblings, and parents of site staff
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 50 mg dose of G03-52-01 G03-52-01 150 subjects randomized to 50 mg of G03-52-01 100 mg dose of G03-52-01 G03-52-01 150 subjects randomized to 100 mg of G03-52-01 Placebo Placebo 75 subjects randomized to placebo 100 mg dose of G03-52-01 or Placebo G03-52-01 250 subjects randomized to 100 mg of G03-52-01 or placebo 100 mg dose of G03-52-01 or Placebo Placebo 250 subjects randomized to 100 mg of G03-52-01 or placebo
- Primary Outcome Measures
Name Time Method Occurrence of changes from baseline in vital signs following administration of G03-52-01 to the final follow-up visit (Cohort 4) 120 Days Number of changes from baselines in vital signs at each visit.
Occurrence of changes from baseline in clinical safety laboratory values following administration of G03-52-01 to the final follow-up visit (Cohort 4) 120 Days Number of changes from baselines in clinical safety labs at visit.
To evaluate the proportion of subjects with target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) at 8 hours post dose (Cohort 4) 1 Day Number of subjects with target protective concentration (NAC) value \> 0.02 U/mL (BoNT/A) or \> 0.03 U/mL (BoNT/B) at 8 hours post dose
To evaluate the proportion of subjects with target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) at Day 45 (Cohorts 1-3) 45 Days Number of subjects with target protective concentration (NAC) value \> 0.02 U/mL (BoNT/A) or \> 0.03 U/mL (BoNT/B) at Day 45
To evaluate the proportion of subjects with target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) at Day 90 (Cohorts 1-3) 90 Days Number of subjects with target protective concentration (NAC) value \> 0.02 U/mL (BoNT/A) or \> 0.03 U/mL (BoNT/B) at Day 90
Occurrence of AEs following administration of G03-52-01 to the final visit (Cohort 4) 120 Days Number of AEs at each visit.
Occurrence of SAEs following administration of G03-52-01 to the final visit (Cohorts 1-3) 240 Days Number of SAEs at each visit.
Occurrence of SAEs following administration of G03-52-01 to the final visit (Cohort 4) 120 Days Number of SAEs at each visit.
Occurrence of changes from baseline in PE following administration of G03-52-01 to the final follow-up visit (Cohorts 1-3) 240 Days Number of changes from baselines in PE at each visit.
Occurrence of changes from baseline in PE following administration of G03-52-01 to the final follow-up visit (Cohort 4) 120 Days Number of changes from baselines in PE at each visit.
Occurrence of AEs following administration of G03-52-01 to the final visit (Cohorts 1-3) 240 Days Number of AEs at each visit.
Occurrence of changes from baseline in clinical safety laboratory values following administration of G03-52-01 to the final follow-up visit (Cohorts 1-3) 240 Days Number of changes from baselines in clinical safety labs at visit.
Occurrence of changes from baseline in vital signs following administration of G03-52-01 to the final follow-up visit (Cohorts 1-3) 240 Days Number of changes from baselines in vital signs at each visit.
To evaluate the proportion of subjects with target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) at 4 hours post dose (Cohort 4) 1 Day Number of subjects with target protective concentration (NAC) value \> 0.02 U/mL (BoNT/A) or \> 0.03 U/mL (BoNT/B) at 4 hours post dose
- Secondary Outcome Measures
Name Time Method To evaluate the proportion of subjects with target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) at 8 hours post dose (Cohort 4) 1 Day Number of subjects with target protective concentration (NAC) value \> 0.02 U/mL (BoNT/A) or \> 0.03 U/mL (BoNT/B) at 8 hours post dose
To evaluate the proportion of subjects with target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) at Day 120 (Cohorts 1-3) 120 Days Number of subjects with target protective concentration (NAC) value \> 0.02 U/mL (BoNT/A) or \> 0.03 U/mL (BoNT/B) at Day 120
Descriptive statistics of selected PD at all timepoints tested (Cohorts 1-3) 120 Days MNA assessments for BoNT serotypes A and B at pre-dose, 24 hours post dose, and on Days 8, 15, 45 (before repeat-dose), 49, 90, and 120
Descriptive statistics of selected ADA at all timepoints tested (Cohorts 4) 240 Days ECLA assessment of ADA titers for each of the mAbs at pre-dose and on Days 15, 45 (before repeat-dose or placebo), 60, 90, 120, 150, 180, and 240
Descriptive statistics of selected PD at all timepoints tested (Cohort 4) 90 Days MNA assessments for BoNT serotypes A and B at pre-dose, 2 hours, 4 hours, 8 hours, 24 hours and on Days 30, 45, and 90
Descriptive statistics of selected ADA at all timepoints tested (Cohorts 1-3) 120 Days ECLA assessment of ADA titers for each of the mAbs at pre-dose and on Days 90 and 120
Descriptive statistics of selected PK at all timepoints tested (Cohorts 4) 120 Days ELISA/ECLA assessment of AUC(0-t) for each of the mAbs at pre-dose, 2 hour, 4 hours, 8 hours, 24 hours, 72 hours post dose, and on Days 8, 15, 30, 45, 90, and 120
Trial Locations
- Locations (15)
AMR Mobile
🇺🇸Mobile, Alabama, United States
AMR Tempe
🇺🇸Tempe, Arizona, United States
AMR Fort Myers
🇺🇸Fort Myers, Florida, United States
AMR Miami
🇺🇸Miami, Florida, United States
AMR El Dorado
🇺🇸El Dorado, Kansas, United States
AMR Newton
🇺🇸Newton, Kansas, United States
AMR Wichita West
🇺🇸Wichita, Kansas, United States
AMR Wichita East
🇺🇸Wichita, Kansas, United States
AMR Lexington
🇺🇸Lexington, Kentucky, United States
AMR New Orleans
🇺🇸New Orleans, Louisiana, United States
AMR Kansas City
🇺🇸Kansas City, Missouri, United States
AMR Las Vegas
🇺🇸Las Vegas, Nevada, United States
AMR Norman
🇺🇸Norman, Oklahoma, United States
AMR Knoxville West
🇺🇸Knoxville, Tennessee, United States
AMR Norfolk
🇺🇸Norfolk, Virginia, United States