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Safety, Tolerability, and PK of a Single Intravenous Dose of ETI-204 in Adult Volunteers

9. januar 2019 oppdatert av: Elusys Therapeutics

A Double-Blind, Randomized, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Dose of ETI-204 in Adult Volunteers

To evaluate the safety and tolerability and pharmacokinetics (PK) of a single intravenous (IV) dose of ETI-204 in adult volunteers.

Studieoversikt

Status

Fullført

Intervensjon / Behandling

Detaljert beskrivelse

A double-blind, randomized, placebo-controlled study of a single IV dose of 16 mg/kg ETI-204 in adult volunteers (210 subjects ETI-204; 70 subjects placebo).

The total duration of the study for each subject will be approximately 100 days divided as follows:

Screening: Days -28 to -2; In-unit Phase: Day -1, Day 1, and Day 2; Out-of-unit Visits: Day 8 (±2 days); Day 15 (±3 days); Day 29 (±3 days); Day 43 (±3 days); Final Visit: Day 71 (±4 days).

Following completion of a screening visit subjects who qualify for entry into the study will be randomized to receive either ETI-204 or matching placebo on Day 1 in a 3:1 ratio. Subjects will be discharged from the clinic on Day 2 following completion of study assessments and will return for five additional visits on Days 8, 15, 29, 43 and 71.

The first 12 subjects will be dosed in groups of no more than 4 subjects/day. A blinded safety review of the available clinical and laboratory AE data up to and including Day 2 will be completed for the first 12 subjects before any additional subjects are dosed. This review will be conducted by the Investigator in conjunction with the Clinical Trial Steering Committee. If the outcome of this review is satisfactory, dosing of additional subjects will be permitted to continue and subjects may be dosed in group sizes larger than 4.

After Amendment 1, premedication with 50 mg oral diphenhydramine approximately 30 minutes prior to the start of study drug infusion was required.

Studietype

Intervensjonell

Registrering (Faktiske)

280

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

    • Texas
      • Dallas, Texas, Forente stater, 75247
        • Covance Clinical Research Inc.

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria:

  1. Females or males ≥ 18 years of age
  2. All females, regardless of childbearing potential, must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test at Screening and Day -1
  3. 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 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
  4. 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
  5. Females who have undergone surgical sterilization, including hysterectomy, bilateral oophorectomy, bilateral salpingectomy, tubal ligation, or tubal essure
  6. 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
  7. Provide written informed consent
  8. Willing to comply with study restrictions

Exclusion Criteria:

  1. Pregnant or lactating woman
  2. Clinically significant comorbidity that would interfere with completion of the study procedures or objectives, or compromise the subject's safety
  3. Seated systolic blood pressure (BP) ≥ 150 mmHg or ≤ 90 mmHg or diastolic BP ≥ 95 mmHg
  4. Use of H1 receptor antagonists (i.e. antihistamines) within 5 days prior to Day 1
  5. Evidence of drug or alcohol abuse as determined by the Investigator within 6 months of Day 1
  6. Positive test result for drugs of abuse (with the exception of medically prescribed drugs) at Screening or on Day -1
  7. Positive test for alcohol at Screening; exclusion is subject to the Investigator's discretion; subjects who test positive for alcohol at Day -1 are excluded from the study
  8. Treatment with an investigational agent within 30 days of Day 1 or within five half-lives of the investigational agent at Day 1 (whichever is longer)
  9. Congenital or acquired immunodeficiency syndrome
  10. Prior solid organ or bone marrow transplant
  11. Positive test for Hepatitis B (surface antigen), Hepatitis C, or human immunodeficiency virus (HIV) at Screening
  12. History of prior treatment for anthrax exposure or prior anthrax infection
  13. 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)
  14. 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
  15. 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
  16. Donation or loss of > 500 mL of blood within 30 days or plasma within 7 days of Day 1
  17. Prior stroke, epilepsy, relapsing or degenerative central nervous system disease, or relapsing or degenerative ocular disease
  18. Myocardial infarction or acute coronary syndrome in the past 5 years, active angina pectoris, or heart failure (New York Heart Association scale > 1)
  19. History of chronic liver disease
  20. Calculated creatinine clearance (CrCl) of < 30 mL/min using the Cockcroft-Gault equation
  21. 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.
  22. History of allergic or hypersensitivity reactions to other therapeutic antibodies or immunoglobulins
  23. 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 (i.e., basal cell carcinoma) or the cervix
  24. 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

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Annen
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Dobbelt

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: ETI-204
A single intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Day 1
Monoclonal Antibody
Placebo komparator: Placebo for ETI-204
A single intravenous dose of ETI-204-placebo infused over 90 minutes on Day 1
Placebo for ETI-204

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Number of Participants Who Experienced Adverse Events
Tidsramme: 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.
Safety was assessed for all subjects in the safety population by collecting and monitoring vital signs, clinical laboratory tests, ECGs, physical examinations, skin assessments, infusion site assessments, and adverse events.
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.

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Maximum Observed Plasma Concentration of ETI-204 (Cmax)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Time to Maximum Observed Plasma Concentration of ETI-204 (Tmax)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration (AUC0-last)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Terminal Half-life (t1/2)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Systemic Clearance (CL)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Volume of Distribution (Vd)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Volume of Distribution at Steady State (Vss)
Tidsramme: On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
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.
On Day 1, prior to the start of infusion, at the end of infusion, and 3 and 8 hours after the start of infusion and on Days 2, 8, 15, 29, 43, and 71.
Number of Participants With Anti-ETI-204 Antibodies
Tidsramme: On Day 1 prior to the start of infusion and on Days 8, 43, and 71.
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.
On Day 1 prior to the start of infusion and on Days 8, 43, and 71.

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Etterforskere

  • Hovedetterforsker: Alex King, MD, Covance
  • Hovedetterforsker: Lori Sieboldt, MD, Covance Clinical Research - Evansville, IN
  • Hovedetterforsker: Debra Mandarino, MD, Covance Research, Madison, WI
  • Hovedetterforsker: H. Frank Farmer, PhD, MD, Covance Research - Daytona Beach, Fl

Publikasjoner og nyttige lenker

Den som er ansvarlig for å legge inn informasjon om studien leverer frivillig disse publikasjonene. Disse kan handle om alt relatert til studiet.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

9. juli 2013

Primær fullføring (Faktiske)

29. november 2013

Studiet fullført (Faktiske)

29. november 2013

Datoer for studieregistrering

Først innsendt

2. august 2013

Først innsendt som oppfylte QC-kriteriene

26. august 2013

Først lagt ut (Anslag)

27. august 2013

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

8. april 2019

Siste oppdatering sendt inn som oppfylte QC-kriteriene

9. januar 2019

Sist bekreftet

1. januar 2019

Mer informasjon

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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