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Completed

NCT Number: NCT01932242

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

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

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Key information

Conditions

Inhalational Anthrax Anthrax Bacillaceae Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Inhalation anthrax

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Quintiles, Overland Park, Kansas, United States

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About this study

A double-blind, randomized, placebo-controlled, study in 70 healthy adult subjects. The total duration of the study for each subject will be approximately 220 days divided as follows:

  • Screening: Days -28 to -2
  • Three In-Unit Stays: Days -1 to 2; Days 13 to 15; and Days 119 to 121
  • Out-of-Unit Visit Days: Day 8 (±2 days); Day 28 (±3 days); Day 43 (±3 days); Day 71 (±3 days); Day 85 (±3 days); Day 128 (±3 days); Day 134 (±3 days); Day 149 (±3 days); and Day 163 (±3 days)
  • Final Visit: Day 191 (±3 days)

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

Subjects who qualify for entry into the study following completion of the Screening visit will arrive at the clinical research unit (CRU) on Day -1. The next day, Day 1, qualified subjects will be randomized and will receive a single IV dose of ETI-204. Subjects will be pretreated with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of the study drug infusion.

Subjects will be discharged from the CRU on Day 2, and will return to the CRU for an additional visit on Day 8.

Subjects will return to the CRU on Day 13 for their second in-unit stay. The next day, Day 14, subjects will be pretreated with 50 mg oral diphenhydramine and will receive study drug according to their randomized treatment assignment. Subjects will be discharged on Day 15 and will return to the CRU for four additional visits on Days 28 (±3 days), 43 (±3 days), 71 (±3 days), and 85 (±3 days).

Subjects will return to the CRU again on Day 119 for their third in-unit stay. On Day 120, subjects will be pretreated with 50 mg oral diphenhydramine and will receive study drug (either ETI 204 or placebo) according to their randomized treatment assignment. Subjects will be discharged on Day 121 and will return to the CRU for five additional visits on Days 128,134, 149, 163, and 191.

The first 20 subjects randomized and treated in the study will be dosed in groups of no more than 4 subjects/day. For the first 8 subjects, dosing of individual subjects on Day 14 and Day 120 will be separated by 30-60 minutes for safety monitoring. If no severe infusion reactions occur in any of the first 8 subjects at the time of the second dose, staggered dosing is not required for the remaining subjects receiving their second dose. Similarly, if no severe infusion reactions occur in any of the first 8 subjects at the time of the third dose, staggered dosing is not required for the remaining subjects receiving their third dose.

Enrollment of additional subjects will be paused until the first 20 subjects have received their second dose of study drug and a blinded review of the available clinical and laboratory AE data up to and including Day 15 is completed for the first 20 subjects. This review will be conducted by the Investigator in conjunction with the Clinical Trial Steering Committee and will focus on the possible development of new or more severe AEs with the Day 14 dose. If the outcome of this review is satisfactory, dosing of additional subjects will be permitted to continue in groups larger than 4 subjects. In the event that significant AEs are observed and unblinding should become necessary, it will be performed by an independent statistician who is not involved with the conduct of the study.

A second blinded safety review will be completed at least two weeks before any subject receives the third dose of study drug, (i.e. before any subject is dosed on Day 120). The Investigator in conjunction with the Clinical Trial Steering Committee will review all AEs seen to date in the study. This review will focus on AE data seen in association with the second infusion (Day14). If the outcome of this review is satisfactory, subjects may receive their third dose of study drug.

A third blinded safety review will be conducted after the initial cohort of 20 subjects has completed Day 121. No additional subjects should receive a third dose of study medication until the Investigator along with the Clinical Trial Steering Committee has completed a blinded safety review of the Day 120 and 121 clinical and laboratory AE data. This review will focus on the development of new or more severe AEs seen with repeat dosing. If the outcome of this review is satisfactory, the remaining subjects may receive their third dose of study drug.

In the event that significant AEs are observed and unblinding becomes necessary it will be performed by an independent statistician who is not involved with the conduct of the study.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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
  • Positive test for alcohol at Screening; exclusion is at the Investigator's discretion; subjects who test positive for alcohol at Day -1 are excluded from the study
  • 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
  • Prior stroke, epilepsy, relapsing or degenerative central nervous system disease, or relapsing or degenerative ocular disease
  • Myocardial infarction or acute coronary syndrome in the past 5 years, active angina pectoris, or heart failure (New York Heart Association scale > 1)
  • History of chronic liver disease
  • Calculated creatinine clearance (CrCl) of < 30 mL/min using the Cockcroft-Gault equation (see Section 5.1)
  • Any clinically significant abnormality, in the Investigator's opinion, on electrocardiogram (ECG) or clinical laboratory tests (hematology, clinical chemistry, or urinalysis) at Screening; Out of range results may be repeated to confirm.
  • History of allergic or hypersensitivity reactions to other therapeutic antibodies or immunoglobulins
  • History of any malignant neoplasm within the last 5 years, with the exception of adequately treated, localized or in situ non-melanoma carcinoma of the skin (e.g., basal cell carcinoma) or the cervix
  • Subjects who, in the opinion of the Investigator, are not suitable candidates for enrollment or who may not comply with the requirements of the study

-

Treatment and study plan

ETI-204

Biological

Monoclonal Antibody

Placebo

Other

Placebo for ETI-204

Primary outcomes

  1. Number of Participants Who Experienced Adverse Events

    Time frame: 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.

    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.

Secondary outcomes

  1. 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)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.The PK parameter, Cmax, was derived from ETI-204 serum concentrations by sequence group and treatment period for the PK analysis population.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120).

    All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

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

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  3. 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)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.The PK parameter, Tmax, was derived from ETI-204 serum concentrations by sequence group and treatment period for the PK analysis population. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

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

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  5. 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)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  6. 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 120 (Sequence B)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  7. Area Under the Concentration-Time Curve From Time Zero to 191 Days (AUC0-191days) After a Dose of 16 mg/kg ETI-204 on Days 1 and 14 (Sequence A)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  8. Area Under the Concentration-Time Curve From Time Zero to 120 Days (AUC0-120days) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B)

    Time frame: On Day 1 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

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

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  10. Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)

    Time frame: On Day 120 prepose, 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  11. Terminal Half-life (t1/2) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  12. Terminal Half-life (t1/2) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.The PK parameter, Cmax, was derived from ETI-204 serum concentrations by sequence group and treatment period for the PK analysis population. Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  13. Systemic Clearance (CL) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  14. Systemic Clearance (CL) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  15. Volume of Distribution (Vd) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B) or Two Doses on Days 1 and 14 (Sequence A)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  16. Volume of Distribution (Vd) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  17. Volume of Distribution at Steady State (Vdss) After a Dose of 16 mg/kg ETI-204 on Day 1 (Sequence B)

    Time frame: On Day 1 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  18. Volume of Distribution at Steady State (Vdss) After a Dose of 16 mg/kg ETI-204 on Day 120 (Sequence B)

    Time frame: 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.

    Blood samples were obtained and serum concentrations were determined using a validated enzyme-linked immunosorbent assay method with an assay range of 100 ng/mL to 5000 ng/mL.

    Sequence A - there were insufficient serum concentration data to adequately characterize ETI 204 PK separately after each dose administration (Day 1 and Day 14), therefore it was treated as one 32 mg/kg dose split into two 16 mg/kg administrations. Sequence B was treated as 2 separate 16 mg/kg doses (Day 1 and Day 120). All 70 subjects who received ETI-204 were included in the PK population: 35 in Sequence A and 35 in Sequence B; however, the full complement of PK parameters could not be determined in all subjects.

  19. Number of Participants With Anti-ETI-204 Antibodies

    Time frame: On Days 1,14, and 120 predose and on Days 8, 43, 85, 128, 163, and 191

    Serum anti-ETI-204 antibody titers were determined for all subjects in the safety population. Blood samples were collected and serum samples were assayed at an initial dilution of 1:10. Samples that were positive at the 1:10 dilution were serially diluted 1:2 and assayed until a negative result was attained. The titer of the most dilute sample yielding a positive result was recorded as the titer for that time point. Immunogenicity was measured by the number of participants in each study arm with anti-ETI-204 antibody values post-treatment ≥ 4-times higher than baseline at Day 8, 43 or 71, or if the titer was negative at baseline, the post-treatment sample(s) required a titer of at least 1:20 for it to be considered positive.

Sponsors and collaborators

Lead sponsor

Elusys Therapeutics

Other

Registry information

Official study title

A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Repeat Administration of Intravenous ETI-204 in Adult Volunteers

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Aug 30, 2013
Registry last updated
May 14, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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