Clinical trial NCT05348993: Single or Repeat Dose of G03-52-01 in Adult Subjects
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Immunogenicity of G03-52-01 in Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Botulinum Toxin
Lead sponsor: Resilience Government Services, Inc.
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2022-04-27
Enrollment: 625
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Single dose of G03-52-01 100 mg or placebo or a repeat dose of G03-52-01 (50mg or 100mg) or placebo on days 1 and 45
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Informed consent understood and signed prior to screening procedures.
2. 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.
3. Able and willing to comply and be available for all protocol procedures and follow-up for the duration of the study.
4. Body Mass Index (BMI) of ≥18.5 and ≤35 kg/m2.
5. 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.
6. 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
7. 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.
8. 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.
9. Breathalyzer test is negative.
10. Available for follow-up for the duration of the study.
11. 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.

Exclusion Criteria:

1. 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).
2. 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.
3. Known allergic reactions to any of the study product components present in the formulation or in the processing.
4. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds).
5. 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.
6. Positive serology results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibodies.
7. 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.
8. 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.
9. Donation of blood or blood product within 56 days of enrollment.
10. 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)
11. 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
12. Treatment with a mAB within 3 months of Day 1.
13. 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.
14. 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.
15. 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).
16. 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.
17. Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or previous treatment with equine antitoxin.
18. 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.
19. 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.
20. 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

Primary outcomes:
measure: Occurrence of AEs following administration of G03-52-01 to the final visit (Cohorts 1-3)
timeFrame: 240 Days
measure: Occurrence of AEs following administration of G03-52-01 to the final visit (Cohort 4)
timeFrame: 120 Days
measure: Occurrence of SAEs following administration of G03-52-01 to the final visit (Cohorts 1-3)
timeFrame: 240 Days
measure: Occurrence of SAEs following administration of G03-52-01 to the final visit (Cohort 4)
timeFrame: 120 Days
measure: Occurrence of changes from baseline in PE following administration of G03-52-01 to the final follow-up visit (Cohorts 1-3)
timeFrame: 240 Days
measure: Occurrence of changes from baseline in PE following administration of G03-52-01 to the final follow-up visit (Cohort 4)
timeFrame: 120 Days
measure: Occurrence of changes from baseline in vital signs following administration of G03-52-01 to the final follow-up visit (Cohorts 1-3)
timeFrame: 240 Days
measure: Occurrence of changes from baseline in vital signs following administration of G03-52-01 to the final follow-up visit (Cohort 4)
timeFrame: 120 Days
measure: 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)
timeFrame: 240 Days
measure: Occurrence of changes from baseline in clinical safety laboratory values following administration of G03-52-01 to the final follow-up visit (Cohort 4)
timeFrame: 120 Days
measure: 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)
timeFrame: 45 Days
measure: 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)
timeFrame: 90 Days
measure: 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)
timeFrame: 1 Day
measure: 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)
timeFrame: 1 Day
Secondary outcomes:
measure: 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)
timeFrame: 120 Days
measure: 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)
timeFrame: 1 Day
measure: Descriptive statistics of selected PD at all timepoints tested (Cohorts 1-3)
timeFrame: 120 Days
measure: Descriptive statistics of selected PD at all timepoints tested (Cohort 4)
timeFrame: 90 Days
measure: Descriptive statistics of selected ADA at all timepoints tested (Cohorts 1-3)
timeFrame: 120 Days
measure: Descriptive statistics of selected ADA at all timepoints tested (Cohorts 4)
timeFrame: 240 Days
measure: Descriptive statistics of selected PK at all timepoints tested (Cohorts 4)
timeFrame: 120 Days
Other outcomes:
measure: Descriptive statistics of selected PK parameters at all time points tested of the two lots
timeFrame: 120 Days
Locations:
city: Mobile
country: United States
facility: AMR Mobile
state: Alabama
city: Tempe
country: United States
facility: AMR Tempe
state: Arizona
city: Fort Myers
country: United States
facility: AMR Fort Myers
state: Florida
city: Miami
country: United States
facility: AMR Miami
state: Florida
city: El Dorado
country: United States
facility: AMR El Dorado
state: Kansas
city: Newton
country: United States
facility: AMR Newton
state: Kansas
city: Wichita
country: United States
facility: AMR Wichita West
state: Kansas
city: Wichita
country: United States
facility: AMR Wichita East
state: Kansas
city: Lexington
country: United States
facility: AMR Lexington
state: Kentucky
city: New Orleans
country: United States
facility: AMR New Orleans
state: Louisiana
city: Kansas City
country: United States
facility: AMR Kansas City
state: Missouri
city: Las Vegas
country: United States
facility: AMR Las Vegas
state: Nevada
city: Norman
country: United States
facility: AMR Norman
state: Oklahoma
city: Knoxville
country: United States
facility: AMR Knoxville West
state: Tennessee
city: Norfolk
country: United States
facility: AMR Norfolk
state: Virginia
Study officials:
References: