Safety, Tolerability and PK of Repeat Administration of Intravenous ETI-204 in Adult Volunteers

NCT01932242 | Completed Phase 1 Results

• 1 other identifier: AH109
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of repeat administration (two doses) of intravenous (IV) ETI-204.

Conditions

Inhalational Anthrax

Keywords

anthrax, monoclonal antibody, ETI-204, safety, PK

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Experienced Adverse Events

  Safety was assessed for all subjects in the safety population by collecting and monitoring vital signs, laboratory tests, ECGs, physical examinations, skin assessments, infusion site assessments and adverse events.

  Up to 191 days or 221 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each arm.

Secondary Outcomes (19)

• Maximum Observed Plasma Concentration of ETI-204 (Cmax) After a Dose of 16 mg/kg on Day 1(Sequence B) or Two Doses on Days 1 and 14 (Sequence A)

  On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.

• Maximum Observed Plasma Concentration of ETI-204 (Cmax) After a Dose of 16 mg/kg on Day 120 (Sequence B)

  On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.

• Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) After a Dose of 16 mg/kg on Day 1(Sequence B) or Two Doses on Days 1 and 14 (Sequence A)

  On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.

• Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax) After a Dose of 16 mg/kg on Day 120 (Sequence B)

  On Day 120 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.

• Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)

  On Days 1 and 14 predose, at the end of infusion, and 3 and 8 hours after the start of infusion, and on Days 2, 8, 15, 28, 43, 71, 85, 121, 128, 134, 149, 163, and 191.

Study Arms (2)

Sequence A

EXPERIMENTAL

An intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Days 1 and 14 and an intravenous dose of ETI-204-Placebo infused over 90 minutes on Day 120.

Biological: ETI-204; Other: Placebo

Sequence B

EXPERIMENTAL

An intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Days 1 and 120 and an intravenous dose of ETI-204-Placebo infused over 90 minutes on Day 14.

Biological: ETI-204; Other: Placebo

Interventions

ETI-204 BIOLOGICAL

Monoclonal Antibody

Sequence A; Sequence B

Placebo OTHER

Placebo for ETI-204

Sequence A; Sequence B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Females or males ≥ 18 years of age
• All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test at Screening and Day -1
• Females of childbearing potential (i.e., not postmenopausal or surgically sterile) must agree to practice abstinence or to use a medically accepted method of contraception from the time of Screening through 30 days after the final study visit. Acceptable methods of contraception include diaphragm with spermicide; sponge with spermicide; condom with spermicide; or intrauterine device with condom or spermicide. The following contraceptive methods are acceptable only when used with a condom and spermicide: birth control pills, birth control patches, vaginal ring, hormone under the skin, or hormone injections
• Postmenopausal females, defined as females who have had amenorrhea for at least 12 months either naturally or following cessation of all exogenous hormonal treatments, and have a follicle-stimulating hormone (FSH) level of \> 40 mIU/mL at Screening
• Females who have undergone surgical sterilization, including hysterectomy, bilateral oophorectomy, bilateral salpingectomy, tubal ligation, or tubal essure
• Males must agree to practice abstinence or use a condom with spermicide and refrain from sperm donation during the study and for 30 days after the final study visit
• Provide written informed consent
• Willing to comply with study restrictions

You may not qualify if:

• Pregnant or lactating woman
• Clinically significant comorbidity that would interfere with completion of the study procedures or objectives or compromise the subject's safety
• Seated systolic blood pressure (BP) ≥ 150 mmHg or ≤ 90 mmHg or diastolic BP ≥ 95 mmHg
• Use of H1 receptor antagonists (i.e. antihistamines) within 5 days prior to Day 1
• Evidence of drug or alcohol abuse as determined by the Investigator within 6 months of Day 1
• Positive test result for drugs of abuse (with the exception of medically prescribed drugs) at Screening or on Day -1
• Treatment with an investigational agent within 30 days or five half-lives of the investigational agent at Day 1 (whichever is longer)
• Congenital or acquired immunodeficiency syndrome
• Prior solid organ or bone marrow transplant
• Positive test for Hepatitis B (surface antigen), Hepatitis C, or human immunodeficiency virus (HIV) at Screening
• History of prior treatment for anthrax exposure or prior anthrax infection
• Prior immunization with any approved or investigational anthrax vaccine or prior treatment with an approved or investigational anthrax treatment (i.e., ETI-204, raxibacumab, or anthrax immune globulin)
• Military personnel deployed in 1990 or after, unless the subject can provide documentation demonstrating they have not previously received any approved or investigational anthrax vaccine
• Use of systemic steroids, immunosuppressive agents, anticoagulants, or anti-arrhythmics within 1 year prior to Day 1. A single short course (i.e., less than 14 days) of systemic steroid therapy is allowed provided it concluded more than 6 months prior to Day 1
• Donation or loss of \> 500 mL of blood within 30 days or plasma within 7 days of Day 1

Sponsors & Collaborators

• Elusys Therapeutics: lead

Study Sites (2)

Quintiles

Overland Park, Kansas, 66211, United States

Location

DaVita

Minneapolis, Minnesota, 55404, United States

Location

Related Publications (1)

• Nagy CF, Leach TS, Hoffman JH, Czech A, Carpenter SE, Guttendorf R. Pharmacokinetics and Tolerability of Obiltoxaximab: A Report of 5 Healthy Volunteer Studies. Clin Ther. 2016 Sep;38(9):2083-2097.e7. doi: 10.1016/j.clinthera.2016.07.170. Epub 2016 Aug 24.

  PMID: 27568215 DERIVED

MeSH Terms

Conditions

Inhalation anthrax; Anthrax

Interventions

obiltoxaximab

Condition Hierarchy (Ancestors)

Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Director of Regulatory
• Organization: Elusys Therapeutics, Inc.

cdillon@elusys.com

973-808-0222

Study Officials

• David Mathews, MD

  Quintiles, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Study drug will be prepared by an unblinded pharmacist not involved with the conduct of the study. The pharmacist will assign the correct study drug (16 mg/kg ETI-204 or placebo) to each subject according to the randomization scheme.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Seventy subjects will be randomized in a 1:1 ratio to one of the following two treatment sequences: * Sequence A: ETI-204 on Days 1 and 14 and placebo on Day 120 * Sequence B: ETI-204 on Days 1 and 120 and placebo on Day 14

Study Record Dates

• First Submitted: August 2, 2013
• First Posted: August 30, 2013
• Study Start: July 23, 2013
• Primary Completion: April 19, 2014
• Study Completion: April 19, 2014
• Last Updated: May 14, 2019
• Results First Posted: April 22, 2019

Record last verified: 2019-01

Locations

US (2)