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Phase 1 Study of SAR440894 vs Placebo

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ClinicalTrials.gov Identifier: NCT04441905
Recruitment Status : Recruiting
First Posted : June 22, 2020
Last Update Posted : March 30, 2021
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
A single, ascending-dose design with five dose-cohorts of 8 subjects. Forty healthy adults aged 18 to 45, inclusive, will be recruited and admitted at one US site. Each subject will be randomized to receive either SAR440894 or matching placebo via 60-minute intravenous infusion. In each cohort of 8 subjects, the randomization ratio will be 6 active to 2 placebo, and 2 sentinel subjects (one from each active and placebo group) will be dosed first. Dosing of the next dose-cohort will be dependent on acceptable meeting predefined safety criteria in the preceding cohort. Each subject's participation will take place over approximately 150 days, not including the screening visit. There are no hypotheses for this phase I study. The primary objective will be to determine the safety of single ascending intravenous (IV) infusions of SAR440894 when administered in healthy adults.

Condition or disease Intervention/treatment Phase
Chikungunya Virus Infection Other: Placebo Biological: SAR440894 Phase 1

Detailed Description:
A single, ascending-dose design with five dose-cohorts of 8 subjects. Forty healthy adults aged 18 to 45, inclusive, will be recruited and admitted at one US site. Each subject will be randomized to receive either SAR440894 or matching placebo via 60-minute intravenous infusion. In each cohort of 8 subjects, the randomization ratio will be 6 active to 2 placebo, and 2 sentinel subjects (one from each active and placebo group) will be dosed first. Dosing of the next dose-cohort will be dependent on acceptable meeting predefined safety criteria in the preceding cohort. Each subject's participation will take place over approximately 150 days, not including the screening visit. There are no hypotheses for this phase I study. The primary objective will be to determine the safety of single ascending intravenous (IV) infusions of SAR440894 when administered in healthy adults. The secondary objectives are: 1) to determine the pharmacokinetics (PK) of single ascending doses of 60-minute IV infusions SAR440894 in healthy adults and 2) to asses the immunogenicity of single ascending doses of 60-minute IV infusions SAR440894 in healthy adults.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1, Randomized, Double-Blind, Single Center, Single Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of SAR440894 vs Placebo in Healthy Adults
Actual Study Start Date : October 14, 2020
Estimated Primary Completion Date : February 26, 2022
Estimated Study Completion Date : February 26, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chikungunya

Arm Intervention/treatment
Experimental: Cohort 1
0.3 mg/kg of SAR440894 (n=6) or placebo (n=2) administered once during a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (SAR440894 n=1, placebo n=1) before remainder of cohort.
Other: Placebo
One time 60-minute IV infusion of lyophilized placebo for SAR440894

Biological: SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus

Experimental: Cohort 2
1 mg/kg of SAR440894 (n=6) or placebo (n=2) administered once during a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (SAR440894 n=1, placebo n=1) before remainder of cohort.
Other: Placebo
One time 60-minute IV infusion of lyophilized placebo for SAR440894

Biological: SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus

Experimental: Cohort 3
3 mg/kg of SAR440894 (n=6) or placebo (n=2) administered once during a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (SAR440894 n=1, placebo n=1) before remainder of cohort.
Other: Placebo
One time 60-minute IV infusion of lyophilized placebo for SAR440894

Biological: SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus

Experimental: Cohort 4
10 mg/kg of SAR440894 (n=6) or placebo (n=2) administered once during a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (SAR440894 n=1, placebo n=1) before remainder of cohort.
Other: Placebo
One time 60-minute IV infusion of lyophilized placebo for SAR440894

Biological: SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus

Experimental: Cohort 5
20 mg/kg of SAR440894 (n=6) or placebo (n=2) administered once during a 60-minute intravenous (IV) infusion. 2 sentinel subjects will receive dosing for review of safety data (SAR440894 n=1, placebo n=1) before remainder of cohort.
Other: Placebo
One time 60-minute IV infusion of lyophilized placebo for SAR440894

Biological: SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus




Primary Outcome Measures :
  1. Occurrence of adverse events (AEs) [ Time Frame: Day 1 through Day 150 ]
  2. Occurrence of changes from baseline in clinical safety laboratory values [ Time Frame: Day 1 through Day 150 ]
    Clinical safety laboratory evaluations include hematology, chemistry, urinalysis, and coagulation.

  3. Occurrence of changes from baseline in vital signs [ Time Frame: Day 1 through Day 150 ]
    Vitals signs include temperature, heart rate, blood pressure, and respiratory rate.

  4. Occurrence of clinically significant changes in ECG parameters from baseline [ Time Frame: Day 1 through Day 150 ]
    Significant changes are defined as the following: Any significant change in rate or rhythm as determined by the site PI, QTcF interval of greater than 450 ms (male) or greater than 460 ms (female), Increase from the QTcF baseline (defined as median of pre-dose measurements) greater than 50 ms until the change resolves.

  5. Occurrence of serious adverse events (SAEs) [ Time Frame: Day 1 through Day 150 ]

Secondary Outcome Measures :
  1. Changes in concentration of SAR440894 plasma human anti-drug antibody (ADA) [ Time Frame: Day 1 through Day 150 ]
    Will be used to determine immunogenicity of SAR440894.

  2. Presence/absence of SAR440894 plasma human anti-drug antibody (ADA) [ Time Frame: Day 1 through Day 150 ]
    Will be used to determine immunogenicity of SAR440894.

  3. SAR440894 plasma concentration [ Time Frame: Day 1 through Day 150 ]
    Plasma concentration will be determined by using a validated enzyme-linked immunosorbent assay. Plasma concentrations will be used to determine plasma PK of SAR440894.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Must be a healthy adult 18 to 45 years of age, inclusive, with a body mass index (BMI) greater than 18 or less than 35 kg/m^2, inclusive.
  2. Participants of childbearing potential* having vaginal intercourse must use an effective method of contraception** from 30 days before study product administration through the final study visit.

    *Not sterilized via hysterectomy or bilateral oophorectomy and/or salpingectomy or be less than 1 year from the last menses if menopausal.

    **Includes any of the following (a) exclusive non-male sexual relationships; (b) monogamous relationship with vasectomized partner (greater than or equal to 180 days between procedure and subject receipt of investigational product); (c) bilateral tubal ligation or tubal occlusion (Essure(R)) with documented radiographic confirmation at 90 days; (d) effective intrauterine device (IUD); (e) hormonal implants (Implanon(R)); (f) other hormonal contraceptives (such as birth control pills, vaginal rings, patches or injections); (g) barrier methods (condom, diaphragm, cervical cap) PLUS spermicide (gel or foam)

  3. Women of childbearing potential must agree not to donate ova or oocytes (ie, human eggs) during the study.
  4. Male subjects (including those with vasectomies) whose partners are of childbearing potential should use condoms with spermicide and not donate sperm for the duration of the study.
  5. Must have adequate venous access for IV infusions and blood draws.
  6. Agrees to be available for all study visits and willing to cooperate fully with the requirements* of the study protocol.

    *Requirements include remaining in confinement for at least 72 hours after receiving study product and other activities outlined in the protocol's Schedule of Events.

  7. Is able to understand the informed consent process and procedures and signs the consent form.
  8. Will agree not to donate any blood or blood products* for the duration of the study.

    • Includes whole blood, red blood cells, platelets, plasma, or plasma derivatives.
  9. Will agree to avoid travel to endemic areas (as defined by the Center for Disease Control (CDC)) for Chikungunya virus at any point during the follow-up period. https://www.cdc.gov/chikungunya/geo/index.html

Exclusion Criteria:

  1. Has any medical condition (e.g., renal dysfunction) that, in the opinion of the site PI or appropriate sub-investigator listed on Food and Drug Administration (FDA) Form 1572, is a contraindication to study participation.
  2. Has any clinically significant (CS) electrocardiogram (ECG) abnormalities in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator been listed on FDA Form 1572?
  3. Use of any prohibited prescription medication (excluding contraceptives in females) within 14 days before study product administration, through Day 56* *Prohibited medications include immunosuppressives; immune modulators; oral corticosteroids (topical/intranasal steroids are acceptable); prescription Non-Steroidal Anti-inflammatory Drugs (NSAIDs); anti-neoplastic agents; any vaccine (licensed or investigational). If study activities overlap with the influenza season, subjects will be instructed to obtain influenza vaccine at least 30 days prior to proposed dosing or delay vaccination until after Day 56.
  4. Use of nonprescription systemic drugs within 7 days before study product administration (includes vitamins, antacids*, over-the-counter drugs**, herbal/dietary supplements, etc.) through Day 28***

    *Nonprescription drugs and supplements may be allowed before Day 28 at the discretion of the site PI.

    **Includes proton pump inhibitors and H2-blockers (Histamine-2 blockers)

    ***Nonprescription drugs and supplements may be allowed before Day 28 at the discretion of the site PI.

  5. Hypertension, with confirmed systolic blood pressure (BP) greater than 140 mm Hg or confirmed diastolic BP greater than 90 mm Hg, measured after 5 minutes of rest at screening.
  6. Hypotension, with confirmed systolic BP less than 90 mm Hg.
  7. Resting heart rate (HR) less than 45 bpm or greater than 100 bpm at screening.
  8. Body weight less than 50 kg.
  9. History of a significant illness, per the investigators' clinical judgment, within 2 weeks before dosing (subjects can screen after illness is resolved for 2 weeks).
  10. Known diagnosis of prolonged QT interval, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
  11. Males with a median QTcF greater than 450 msec or females with a median QTcF greater than 460 msec (Fridericia's correction) at Screening.*

    *ECG tracings should be recorded at least 1 minute apart, after at least 5 minutes of rest in the supine position. If the median QTcF value from the 3 tracings exceeds the limits stated, the subject is disqualified.

  12. Any history of malignancy ever, except low-grade skin cancer (ie, basal cell carcinoma thought to be cured).
  13. History of drug abuse, alcohol abuse, or significant psychiatric history according to the investigators' judgment within 12 months before Screening.
  14. Positive screen for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody.
  15. Excessive consumption of beverages containing xanthine bases, or more than 400 mg of caffeine per day within 1 week of study product administration through the final study visit.
  16. Consumption of alcohol within 24 hours before study product administration.
  17. Use of nicotine-containing products within 30 days before study product administration through the final study visit.
  18. Positive drug screen*, positive cotinine screen, or positive breathalyzer test for alcohol at Screening or admission (Day -1).

    *Cannabinoids, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and phencyclidine. Subjects should be notified by phone not to consume any poppy seeds within 24 hours before the screening urine test to avoid a false positive opioid test result.

  19. If female, serum positive pregnancy test at Screening or serum positive pregnancy test on Day -1.
  20. Breastfeeding throughout the duration of the study
  21. Total WBC and platelet counts, hemoglobin, total bilirubin, alanine/aspartate aminotransferase and sodium* are Grade 1 or higher** at Screening visit.

    *For sodium only; Grade 1 lower limit values (132-134 mmol/L) will be allowed at Screening and Day -1/baseline. If the result is Grade 1 at screening, the participant will be scheduled to repeat the test during the screening period but before Day-1 to assure that it is at or > the initial measurement. Sodium values below 132 mmol/L are exclusionary

    **Grade 1 or higher toxicity, see Appendix C or Appendix D. Safety laboratory tests drawn on Day -1 or Screening if within 48 hours of planned dosing will serve as baseline values. Day -1 laboratory tests with a Grade 1 severity will not exclude subjects from participation.

  22. Potassium, bicarbonate or creatinine results are Grade 1 or higher at either Screening or Day -1/Baseline visits.
  23. Received an experimental agent (vaccine, drug, biologic, device, or medication) within 30 days or 5 half-lives (whichever is longer) before study product administration.*

    *Prior participation at any time in noninvasive methodology trials in which no drugs were given is acceptable.

  24. Is participating in or plans to participate in another clinical trial with an interventional agent that will be received during this trial.
  25. Has donated more than 500 mL of blood or blood products* within the month before Screening.

    *Includes whole blood, red blood cells, platelets, plasma, or plasma derivatives.

  26. Has a history of serologically-proven Chikungunya virus (CHIKV) exposure at any point, or positive anti CHIKV antibodies at Screening.
  27. Has received blood products within 120 days prior to Screening.
  28. Has received any mAb in the past, whether licensed or investigational, or plans to receive a mAb during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04441905


Contacts
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Contact: Michael Cohen-Wolkowiez 19196688812 michael.cohenwolkowiez@duke.edu

Locations
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United States, North Carolina
Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit Recruiting
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04441905    
Other Study ID Numbers: 18-0006
HHSN272201500006I
First Posted: June 22, 2020    Key Record Dates
Last Update Posted: March 30, 2021
Last Verified: March 27, 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Chikungunya Virus
dose escalation
healthy adults
Immunogenicity
Pharmacokinetics
phase 1
placebo
SAR440894
Additional relevant MeSH terms:
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Chikungunya Fever
Virus Diseases
Alphavirus Infections
Togaviridae Infections
RNA Virus Infections