- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03603665
A Study to Evaluate the Safety and Pharmacokinetics of NTM-1633 vs Placebo Administered Intravenously in Healthy Adults
A Phase I, Double-Blind, Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of NTM-1633 vs Placebo Administered Intravenously in Healthy Adults
Study Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
North Carolina
-
Durham, North Carolina, United States, 27710-4000
- Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Informed consent understood and signed.
- Healthy male or healthy, non-pregnant, non-lactating female.
- Willingness to comply and be available for all protocol procedures including inpatient confinement for 36 - 48 hours.
- Age between 18 and 45 years, inclusive on the day of infusion.
- Body Mass Index (BMI) of > / =18.5 and < 35 kg/m^2.
If the subject is female and of childbearing potential, she has a negative serum pregnancy test at screening and negative urine test within 24 hours prior to infusion.
- 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 or successful Essure placement with documented confirmation test at least 3 months after the procedure.
If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men or use acceptable contraception up to visit 12 of the study.
- Acceptable contraception methods are restricted to effective devices (Intrauterine Contraceptive Devices, NuvaRing(R)) or licensed hormonal products with use of method for a minimum of 28 days prior to dosing, condoms or diaphragm with spermicidal agents, monogamous relationship with a vasectomized partner
- The hemoglobin, platelet count, white blood cell count and absolute neutrophil count are within normal limits at the screening visit.
The urine dipstick results on protein, glucose and blood are negative or trace.
- Menstruating females failing inclusion criteria due to a positive blood on urine dipstick may be retested following cessation of menses.
Chemistry screening laboratory tests are in the normal reference range.
The following exceptions to laboratory normal reference ranges are allowed: Creatinine, Blood Urea Nitrogen (BUN), total bilirubin, AST, ALT, lipase, amylase, Prothrombin Time (PT), Partial Thromboplastin Time (PTT) below the lower limit of normal (LLN); CK less than 400mg/ml; Glucose, potassium, total protein, and alkaline phosphatase with a toxicity grade of 1 is allowable; albumin above the upper limit of normal (ULN).
- 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.
- Abnormalities in mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), mean platelet volume (MPV), and nucleated red blood cell count (NRBC CT), which are included in a complete blood count with differential, will not be exclusionary.
- Has adequate venous access for the infusion.
- The urine drug screen is negative.
- Breathalyzer test is negative.
- Available for follow-up for the duration of the study.
- Agrees not to participate in vigorous activity 72 hours prior to dosing through day 15 post dosing.
Exclusion Criteria:
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 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)
History of severe allergic reaction of any type to medications, bee stings, food, or environmental factors or hypersensitivity or reaction to immunoglobulins.
- Note: Severe allergic reaction is defined as any of the following: anaphylaxis, urticaria, or angioedema
- A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 milliseconds)
Clinically significant abnormal electrocardiogram at screening.
- Clinically significant abnormal ECG results include: complete left or right bundle branch block; other ventricular conduction block; 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 HIV, HBsAg, or HCV antibodies
- Febrile illness with temperature > 37.6 degrees Celsius within 7 days of dosing
- Pregnant or breastfeeding
- Donated blood within 56 days of enrollment (day -1)
- Known allergic reactions to any of the study product components present in the formulation or in the processing, as listed in the Investigator Brochure
- Treatment with another investigational drug within 28 days of dosing
- Treatment with a monoclonal antibody at any time in the past
- Receipt of antibody (e.g. TIG, VZIG, IVIG, IM gamma globulin) or blood transfusion within 6 months or within 5 half-lives of the specific product given
- Active drug or alcohol use or dependence 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
Use of any prohibited medication within 28 days prior to study entry or planned use during the study period
- Prohibited medications include immunosuppressives (except Nonsteroidal Anti-Inflammatory Drugs [NSAIDS]); immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); anti-neoplastic agents; any vaccine (licensed or investigational). If study activities overlap with the influenza season, subjects will be instructed to delay influenza vaccination until after Day 57 (Visit 11)
- Previous exposure to botulinum toxin, receipt of antibodies against botulinum toxin, or previous treatment with equine antitoxin
- Any previous injection or planned injection within 4 months after enrollment of botulinum toxin for cosmetic reasons, spastic dysphonia, torticollis, or any other reason
- Any specific condition that in the judgment of the investigator precludes participation because it could affect subject safety
Plans to enroll or is already enrolled in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period
- Includes trials that have a study intervention such as a drug, biologic, or device
Is a study site employee or staff who are paid entirely or partially by the OCRR contract for the DMID-funded trial
- Site employees or staff include the PIs and sub-investigators or staff who are supervised by the PI or Sub-Investigators
- Systolic blood pressure >140 mm Hg or diastolic blood pressure > 90 mm Hg
- Resting heart rate < 50 or > 100 beats per minute at Screening
- Oral temperature > / = 38 degrees Celsius (100.4 degrees Fahrenheit)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm A
Single intravenous (IV) infusion of 0.033 mg/kg NTM-1633 (N=6) or matching Placebo (N=2) using an infusion pump over 60 minutes
|
NTM-1633 is an equimolar mixture of three IgG1 monoclonal antibodies (mAb), referred to as XE02, XE06, and XE17 which bind to non-overlapping epitopes on Botulinum Neurotoxin (BoNT/E).
Administered as a single intravenous infusion of NTM-1633 over one hour.
0.9% Sodium Chloride Injection administered as a single intravenous infusion over one hour.
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Experimental: Arm B
Single IV infusion of 0.165 mg/kg NTM-1633 (N=6) or matching Placebo (N=2) using an infusion pump over 60 minutes
|
NTM-1633 is an equimolar mixture of three IgG1 monoclonal antibodies (mAb), referred to as XE02, XE06, and XE17 which bind to non-overlapping epitopes on Botulinum Neurotoxin (BoNT/E).
Administered as a single intravenous infusion of NTM-1633 over one hour.
0.9% Sodium Chloride Injection administered as a single intravenous infusion over one hour.
|
Experimental: Arm C
Single IV infusion of 0.330 mg/kg NTM-1633 (N=6) or matching Placebo (N=2) using an infusion pump over 60 minutes
|
NTM-1633 is an equimolar mixture of three IgG1 monoclonal antibodies (mAb), referred to as XE02, XE06, and XE17 which bind to non-overlapping epitopes on Botulinum Neurotoxin (BoNT/E).
Administered as a single intravenous infusion of NTM-1633 over one hour.
0.9% Sodium Chloride Injection administered as a single intravenous infusion over one hour.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
The occurrence of AEs
Time Frame: From Day 1 through Day 57
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From Day 1 through Day 57
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The occurrence of changes in absolute neutrophil count
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in alanine transaminase (ALT) level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in aldolase level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in alkaline phosphatase level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in aspartate transaminase (AST) level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in blood urea nitrogen (BUN) level
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in calcium level
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in Complete Blood Count (CBC) with differential
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in diastolic blood pressure in arm A
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in diastolic blood pressure in arms B and C
Time Frame: From Day -1 through Day 121
|
From Day -1 through Day 121
|
The occurrence of changes in direct bilirubin level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in heart rate in arm A
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in heart rate in arms B and C
Time Frame: From Day -1 through Day 121
|
From Day -1 through Day 121
|
The occurrence of changes in hemoglobin level
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
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The occurrence of changes in indirect bilirubin level
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in oral temperature in arm A
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in oral temperature in arms B and C
Time Frame: From Day -1 through Day 121
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From Day -1 through Day 121
|
The occurrence of changes in physical examination in arm A
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
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The occurrence of changes in physical examination in arms B and C
Time Frame: From Day -1 through Day 121
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From Day -1 through Day 121
|
The occurrence of changes in platelet count
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
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The occurrence of changes in potassium level
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in prothrombin time/international normalized ratio (INR)
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in serum creatinine level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in sodium level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in systolic blood pressure in arm A
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in systolic blood pressure in arms B and C
Time Frame: From Day -1 through Day 121
|
From Day -1 through Day 121
|
The occurrence of changes in total bilirubin level
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
|
The occurrence of changes in total creatine kinase (CK) level
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of changes in White Blood Cell (WBC) count
Time Frame: From Day -1 through Day 91
|
From Day -1 through Day 91
|
The occurrence of clinically significant ECG abnormalities
Time Frame: From Day -28 through Day 1
|
From Day -28 through Day 1
|
The occurrence of QT interval abnormalities
Time Frame: From Day -28 through Day 1
|
From Day -28 through Day 1
|
The occurrence of SAEs in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
The occurrence of SAEs in arms B and C
Time Frame: From Day 1 through Day 121
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From Day 1 through Day 121
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The presence of protein, blood, or glucose in urine
Time Frame: From Day -1 through Day 91
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From Day -1 through Day 91
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE02 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE02 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE06 in arm A
Time Frame: From Day 1 through Day 91
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From Day 1 through Day 91
|
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE06 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE17 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Area under the plasma concentration-time curve (AUC) from time 0 up to the last observed concentration at time t (AUC0-t) for XE17 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Maximum observed plasma concentration (Cmax) for XE02 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Maximum observed plasma concentration (Cmax) for XE02 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Maximum observed plasma concentration (Cmax) for XE06 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Maximum observed plasma concentration (Cmax) for XE06 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Maximum observed plasma concentration (Cmax) for XE17 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Maximum observed plasma concentration (Cmax) for XE17 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
The presence of human anti-human antibodies (HAHA)
Time Frame: Day 1
|
Day 1
|
The presence of human anti-human antibodies (HAHA)
Time Frame: Day 29
|
Day 29
|
The presence of human anti-human antibodies (HAHA)
Time Frame: Day 57
|
Day 57
|
The presence of human anti-human antibodies (HAHA)
Time Frame: Day 91
|
Day 91
|
The presence of human anti-human antibodies (HAHA) for Arms B and C
Time Frame: Day 121
|
Day 121
|
Time to maximum observed plasma concentration (Tmax) for XE02 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Time to maximum observed plasma concentration (Tmax) for XE02 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Time to maximum observed plasma concentration (Tmax) for XE06 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Time to maximum observed plasma concentration (Tmax) for XE06 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Time to maximum observed plasma concentration (Tmax) for XE17 in arm A
Time Frame: From Day 1 through Day 91
|
From Day 1 through Day 91
|
Time to maximum observed plasma concentration (Tmax) for XE17 in arms B and C
Time Frame: From Day 1 through Day 121
|
From Day 1 through Day 121
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 14-0023
- HHSN272201300017I
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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