Repeat Dose of G03-52-01 in Adult Subjects

Study Overview
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Brief Summary
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A Phase 2, randomized, double-blind, placebo-controlled repeat dose trial

Detailed Description
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A Phase 2, multicenter, randomized, double-blinded, placebo-controlled study to evaluate repeat dose (50 mg and 100 mg) of G03-52-01 administered by IM injection(s) in adult subjects. Approximately 375 subjects will be enrolled in this study.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Immunogenicity of a Repeat Dose of G03-52-01 in Adult Subjects

Conditions
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Healthy, Botulinum Toxin

Intervention / Treatment
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* Drug: G03-52-01
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent understood and signed prior to screening procedures. 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. Able and willing to comply and be available for all protocol procedures and follow-up for the duration of the study. Body Mass Index (BMI) of ≥18.5 and ≤35 kg/m2. 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. 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 Intrauterine device (IUD) or intrauterine system 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. The urine drug screen is negative. • 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. Breathalyzer test is negative. Available for follow-up for the duration of the study. Agrees not to participate in vigorous activity 2 days prior to dosing and 2 days post-dose Day 1 and Day 45, per Investigator discretion. Exclusion Criteria: History of any uncontrolled or chronic medical conditions that would either interfere with the accurate assessment of the objectives of the study or increase the risk profile of the subject based on Investigator judgement. • Chronic medical conditions include but 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). 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 reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema. Known allergic reactions to any of the study product components present in the formulation or in the processing. 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 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. Positive serology results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies at screening. 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. 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 visit. Donation of blood or blood product within 56 days of enrollment. 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). 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 Treatment with a monoclonal antibody (mAB) within 3 months of Day 1. 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. 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. Use of H1 antihistamines or beta-blockers within 5 days of dosing Day 1 and Day 45 (PRN use could be allowed with MM approval). Use of any prohibited medication within 28 days prior to study entry or planned use during the study period. • Prohibited medications include immunosuppressive (except nonsteroidal anti-inflammatory drugs [NSAIDs]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents. Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or previous treatment with equine antitoxin. 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. 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. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: repeat dose of G03-52-01 (50mg or 100mg) or placebo on days 1 and 45
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50 mg dose of G03-52-01<br>150 subjects randomized to 50 mg of G03-52-01 | Drug: G03-52-01<br>* G03-52-01 administered intramuscularly<br>|
| Experimental: 100 mg dose of G03-52-01<br>150 subjects randomized to 100 mg of G03-52-01 | Drug: G03-52-01<br>* G03-52-01 administered intramuscularly<br>|
| Placebo Comparator: Placebo<br>75 subjects randomized to placebo | Drug: Placebo<br>* placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of AEs following administration of G03-52-01 to the final visit | Number of AEs at each visit. | 240 Days | 
| Occurrence of SAEs following administration of G03-52-01 to the final visit | Number of SAEs at each visit. | 240 Days | 
| Occurrence of changes from baseline in PE following administration of G03-52-01 to the final follow-up visit | Number of changes from baselines in PE at each visit. | 240 Days | 
| Occurrence of changes from baseline in vital signs following administration of G03-52-01 to the final follow-up visit | Number of changes from baselines in vital signs at each visit. | 240 Days | 
| Occurrence of changes from baseline in clinical safety laboratory values following administration of G03-52-01 to the final follow-up visit | Number of changes from baselines in clinical safety labs at visit. | 240 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 45 | MNA assessment of AUC (0-t) for BoNT serotypes A and B at Day 45. | 45 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 45 | MNA assessment of Cmax for BoNT serotypes A and B at Day 45. | 45 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 45 | MNA assessment of Tmax for BoNT serotypes A and B at Day 45. | 45 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 90 | MNA assessment of AUC (0-t) for BoNT serotypes A and B at Day 90. | 90 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 90 | MNA assessment of Cmax for BoNT serotypes A and B at Day 90. | 90 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 90 | MNA assessment of Tmax for BoNT serotypes A and B at Day 90. | 90 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 120 | MNA assessment of AUC (0-t) for BoNT serotypes A and B at Day 120 | 120 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 120 | MNA assessment of Cmax for BoNT serotypes A and B at Day 120 | 120 Days | 
| Target protective concentration (NAC) value > 0.02 U/mL (BoNT/A) or > 0.03 U/mL (BoNT/B) measured by MNA for BoNT serotypes A and B at Day 120 | MNA assessment of Tmax for BoNT serotypes A and B at Day 120 | 120 Days | 
| Descriptive statistics of selected PD and ADA at all timepoints tested | MNA assessment of AUC (0-t) 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 ECLA assessment of ADA titers for each of the mAbs at pre-dose and Days 15, 45 (before repeat-dose or placebo), 60, 90, 120, 150, 180, and 240 | 240 Days | 
| Descriptive statistics of selected PD and ADA at all timepoints tested | MNA assessment of Cmax 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 ECLA assessment of ADA titers for each of the mAbs at pre-dose and Days 15, 45 (before repeat-dose or placebo), 60, 90, 120, 150, 180, and 240 | 240 Days | 
| Descriptive statistics of selected PD and ADA at all timepoints tested | MNA assessment of Tmax 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 ECLA assessment of ADA titers for each of the mAbs at pre-dose and Days 15, 45 (before repeat-dose or placebo), 60, 90, 120, 150, 180, and 240 | 240 Days |