Study to Evaluate Safety and PK of NTM-1634 vs Placebo Administered Intravenously in Healthy Adults

NCT03046550 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: NTM-1634-001272201600009C-2-0-1
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the safety and pharmacokinetics of NTM-1634 in healthy subjects.

Conditions

Healthy

Outcome Measures

Primary Outcomes (6)

• The occurrence of Serious Adverse Events following administration of NTM-1634 to the final follow-up visit

  number of SAE

  121 days

• The occurrence of Adverse Events from administration of NTM-1634 to Day 57

  number of AE

  57 days

• The occurrence of changes from baseline in physical examination following administration of NTM-1634 to the final follow-up visit

  types of changes of physical exam findings

  121 days

• The occurrence of changes from baseline in vital signs following administration of NTM-1634 to the final follow-up visit

  change in vital signs

  121 day

• The occurrence of changes from baseline in clinical safety laboratory values following administration of NTM-1634 to the final follow-up visit

  change in lab values

  121 day

• The occurrence of changes from baseline in ECG parameters post administration of NTM-1634 on Day 1 (day of infusion)

  changes in ECG parameters

  1 day

Secondary Outcomes (4)

• The assessment of Cmax for each of the four monoclonal antibodies of NTM-1634

  121 days

• The assessment of Tmax for each of the four monoclonal antibodies of NTM-1634

  121 days

• The assessment of AUC(0-t) for each of the four monoclonal antibodies of NTM-1634

  121 days

• Development of human anti-human antibodies (HAHA) via blood collection at Days 1, 29, 57, 91 and 121.

  Days 1, 29, 57, 91, and 121

Study Arms (3)

Cohort A

EXPERIMENTAL

Cohort A will have 8 total subjects. 6 subjects will receive 0.33 mg/kg of NTM-1634 and 2 subjects will receive placebo.

Drug: NTM-1634; Drug: Placebo

Cohort B

EXPERIMENTAL

Cohort B will have 8 total subjects. 6 subjects will receive 0.66 mg/kg of NTM-1634 and 2 subjects will receive placebo.

Drug: NTM-1634; Drug: Placebo

Cohort C

EXPERIMENTAL

Cohort C will have 8 total subjects. 6 subjects will receive 1 mg/kg of NTM-1634 and 2 subjects will receive placebo.

Drug: NTM-1634; Drug: Placebo

Interventions

NTM-1634 DRUG

NTM-1634 drug product is a mixture of four human monoclonal IgG1 antibodies. Three dose cohorts (A: 0.33 mg/kg B: 0.66 mg/kg, and C: 1 mg/kg).

Cohort A; Cohort B; Cohort C

Placebo DRUG

placebo

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years - 48 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 ≤30 kg/m2
• If the subject is female and of childbearing potential, she has a negative urine pregnancy test at screening and negative serum test within 24 hours prior to infusion
• Note: 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
• Note: Acceptable contraception methods are restricted to effective devices (Intrauterine Contraceptive Devices , NuvaRing®)
• The hemoglobin, platelet count, white blood cell count and absolute neutrophil count are within normal limits
• The urine dipstick results on protein, glucose and blood are negative or trace
• Chemistry screening laboratory tests as outlined in Section 7.5.1.4 are in the normal reference range
• Note: 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.
• Has adequate venous access for the infusion

You may not qualify if:

• 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.
• Note: 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.
• Note: 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 ≥38°C within 7 days of dosing
• Pregnant or breastfeeding
• Donated blood within 56 days of enrollment
• 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
• 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

Sponsors & Collaborators

• Alachua Government Services, Inc.: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

ICON Early Phase Services, LLC

San Antonio, Texas, 78209, United States

Location

Study Officials

• Dennis Ruff, MD

  ICON Early Phase Services, LLC

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 1, 2017
• First Posted: February 8, 2017
• Study Start: March 20, 2017
• Primary Completion: October 30, 2017
• Study Completion: October 30, 2017
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)