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

9 gennaio 2019 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

280

Fase

  • Fase 1

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

    • Texas
      • Dallas, Texas, Stati Uniti, 75247
        • Covance Clinical Research Inc.

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Altro
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: ETI-204
A single intravenous dose of 16 mg/kg ETI-204 infused over 90 minutes on Day 1
Monoclonal Antibody
Comparatore placebo: Placebo for ETI-204
A single intravenous dose of ETI-204-placebo infused over 90 minutes on Day 1
Placebo per ETI-204

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants Who Experienced Adverse Events
Lasso di tempo: 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.

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Maximum Observed Plasma Concentration of ETI-204 (Cmax)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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.

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Investigatori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

9 luglio 2013

Completamento primario (Effettivo)

29 novembre 2013

Completamento dello studio (Effettivo)

29 novembre 2013

Date di iscrizione allo studio

Primo inviato

2 agosto 2013

Primo inviato che soddisfa i criteri di controllo qualità

26 agosto 2013

Primo Inserito (Stima)

27 agosto 2013

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

8 aprile 2019

Ultimo aggiornamento inviato che soddisfa i criteri QC

9 gennaio 2019

Ultimo verificato

1 gennaio 2019

Maggiori informazioni

Termini relativi a questo studio

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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