Safety, Tolerability and PK of Intravenous (IV) ETI-204 Alone and in Presence of Ciprofloxacin in Adult Volunteers

NCT01952444 | Completed Phase 1 Results

• 1 other identifier: AH110
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) ETI-204 alone and in the presence of IV and oral ciprofloxacin

Conditions

Inhalational Anthrax

Keywords

monoclonal antibody, ETI-204, ciprofloxacin, 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, clinical laboratory tests, ECGs, physical assessments, skin assessments, infusion site assessments, and adverse events (AEs).

  Up to 71 days or 101 days (30 days after the final study visit) for subjects with ongoing adverse events at the final study visit, for each group.

Secondary Outcomes (9)

• Maximum Observed Plasma Concentration of ETI-204 (Cmax)

  On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.

• Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)

  On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.

• Area Under the Concentration-Time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last))

  On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.

• Area Under the Concentration-Time Curve From Time 0 to Infinity (AUC0-inf)

  On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.

• Terminal Half-life (t1/2)

  On Day 1 at predose, at the end of ETI-204 infusion, 2.5, 4.5 and 7.5 hours after the start of the ETI-204 infusion, and on Days 2 (24 hours), 9, 16, 29, 43, and 71.

Study Arms (2)

Group 1 ETI-204 and Ciprofloxacin

EXPERIMENTAL

Participants will receive a single IV dose of 16 mg/kg ETI-204 infused over 90 minutes on Day 1, immediately followed by an IV dose of ciprofloxacin 400 mg infused over 60 minutes, followed by oral doses of ciprofloxacin (750 mg every 12 hours) from Day 2 to Day 8 and a final dose on the morning of Day 9.

Biological: ETI-204; Drug: Ciprofloxacin

Group 2 ETI-204 Alone

OTHER

Participants will receive a single IV dose of 16 mg/kg ETI-204 infused over 90 minutes on Day 1.

Biological: ETI-204

Interventions

ETI-204 BIOLOGICAL

A single IV infusion of 16 mg/kg ETI-204 over 90 minutes on Day 1

Also known as: Obiltoxaximab

Group 1 ETI-204 and Ciprofloxacin; Group 2 ETI-204 Alone

Ciprofloxacin DRUG

A single IV Infusion of 400 mg Ciprofloxacin over 60 minutes immediately following the infusion of ETI-204 on Day 1, followed by oral Ciprofloxacin (750 mg every 12 hours) on Days 2-8, and a final oral dose on the morning of Day 9.

Group 1 ETI-204 and Ciprofloxacin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Females or males between 18 and 60 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
• 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. Note this does not apply to males who have undergone a vasectomy and can provide documentation of confirmatory sperm count 3 months post procedure.
• Provide written informed consent
• Willing to comply with study restrictions (see Section 4.5.3 for a complete list of 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
• Supine 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
• Positive test for alcohol at Screening or 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 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
• Therapeutic 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

Sponsors & Collaborators

• Elusys Therapeutics: lead

Study Sites (1)

Quintiles

Overland Park, Kansas, 66211, 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

Interventions

obiltoxaximab; Ciprofloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

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

• Jolene Berg, MD

  Davita Clinical Research

  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: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2013
• First Posted: September 30, 2013
• Study Start: October 29, 2013
• Primary Completion: April 9, 2014
• Study Completion: April 9, 2014
• Last Updated: April 16, 2019
• Results First Posted: April 8, 2019

Record last verified: 2019-01

Locations

US (1)