- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04441905
Phase 1 Study of SAR440894 vs Placebo
A Phase 1, Randomized, Double-Blind, Multi-Site, Single Dose Escalation Study to Evaluate the Safety, Pharmacokinetics, and Immunogenicity of SAR440894 vs Placebo in Healthy Adults
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Kristie Miller
- Phone Number: 15127471504
- Email: kristie.miller@ppd.com
Study Locations
-
-
Florida
-
Orlando, Florida, United States, 32806
- Pharmaceutical Product Development - Orlando Clinical Research Unit
-
-
North Carolina
-
Durham, North Carolina, United States, 27710
- Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit
-
-
Texas
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Austin, Texas, United States, 78744-1645
- PPD - Austin Clinical Research Unit
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
Participants of childbearing potential* having vaginal intercourse must use an effective method of contraception** from 45 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 (eg., Essure(R)); (d) effective intrauterine device (IUD); (e) hormonal implants (eg., 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)
- Women of childbearing potential must agree not to donate ova or oocytes (ie, human eggs) during the study.
- 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.
- Must have adequate venous access for IV infusions and blood draws.
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.
- Is able to understand the informed consent process and procedures and signs the consent form.
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.
- Will agree to avoid travel to endemic areas (as defined by the Center for Disease Control (CDC)) for Chikungunya Virus (CHIKV) at any point during the Follow-up period (https://www.cdc.gov/chikungunya/geo/index.html).
Exclusion Criteria:
- Has any medical condition (renal dysfunction) that, in the opinion of the site PI or appropriate sub-investigator listed on Form Food and Drug Administration (FDA) 1572, is a contraindication to study participation.
- Has any clinically significant (CS) electrocardiogram (ECG) abnormalities in the opinion of the site Principal Investigator (PI) or appropriate sub-investigator been listed on Form FDA 1572.
- 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 45 days prior to proposed dosing or delay vaccination until after Day 56. Subjects will be instructed to obtain the last dose of any vaccine for SARS-CoV-2 (COVID-19) at least 45 days prior to proposed dosing or delay vaccination until after Day 56.
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. In the event an OTC oral contraceptive becomes available during the course of the study, it must be reviewed and approved by the site PI.
- 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.
- Hypotension, with confirmed systolic BP less than 90 mm Hg.
- Resting heart rate (HR) less than 45 bpm or greater than 100 bpm at Screening.
- Body weight less than 50 kg.
- 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).
- Known diagnosis of prolonged QT interval, congenital long QT syndrome, bradyarrhythmias, or uncompensated heart failure.
Males with a mean QTcF greater than 450 msec or females with a mean QTcF greater than 470 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 mean QTcF value from the 3 tracings exceeds the limits stated, the subject is disqualified.
- Any history of malignancy ever, except low-grade skin cancer (ie, basal cell carcinoma thought to be cured).
- History of drug abuse, alcohol abuse, or significant psychiatric history according to the investigators' judgment within 12 months before Screening.
- Positive for hepatitis B virus surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody at Screening.
- 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.
- Consumption of alcohol within 24 hours before study product administration.
- Use of nicotine-containing products within 45 days before study product administration through the final study visit.
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.
- If female, serum positive pregnancy test at Screening or serum positive pregnancy test on Day -1.
- Breastfeeding throughout the duration of the study
Total WBC and platelet counts, hemoglobin*, total bilirubin*, alanine/aspartate aminotransferase* and sodium* are Grade 1 or higher** at Screening visit***.
*For sodium; potential subjects excluded prior to Protocol Version 6.0 with Grade 1 sodium values may be rescreened.
For hemoglobin; a lower limit within 0.5 g/dL of the lower limit of normal (LLN) is allowable at Screening.
For total bilirubin; ULN values will be allowed at Screening and Day -1/baseline provided the AST and ALT are within normal limits. Potential subjects excluded prior to Protocol Version 6.0 with bilirubin values below the Version 6.0 upper limit may be rescreened.
- For ALT/AST; subjects who screened prior to Protocol Version 11.0 were excluded if AST/ALT results were Grade 1 or higher at Screening. Subjects who screen with Protocol Version 11.0, AST/ALT is exclusionary if Screening results are 1.5 × ULN or if assessed as CS by the site PI.
Grade 1 or higher toxicity, see Appendix C and Appendix D for subjects who screened and enrolled prior to Protocol Version 11.0. Subjects who screen and enroll with Protocol Version 11.0, toxicity will be assessed with the NCI CTCAE, Version 5.0 - November 2017. 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, other than those noted above, will not exclude subjects from participation.
- All other abnormal laboratory values collected at Screening and on Day -1 will be exclusionary at the discretion of the PI.
Potassium, bicarbonate or creatinine/eGFR* results are Grade 1 or higher at either Screening or Day -1/Baseline visits.
*For creatinine; subjects who screened prior to Protocol Version 11.0 were excluded if creatinine results were Grade 1 or higher. Subjects who screen with Protocol Version 11.0, creatinine is not an exclusionary criterion, instead subjects should have a calculated eGFR using Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation (CKD-EPI) of >/= 90 mL/min/1.73m2 to be enrolled in the study.
Received an experimental agent (vaccine, drug, biologic, device, or medication) within 45 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.
- Is participating in or plans to participate in another clinical trial with an interventional agent that will be received during this trial.
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.
- Has a history of serologically-proven Chikungunya virus (CHIKV) exposure at any point, or positive anti CHIKV antibodies (ie., positive IgM or IgG) at Screening.
- Has received blood products within 120 days prior to Screening.
- Has received mAb in the past 3-months or 5 half-lives (whichever is longer) prior to Screening, whether licensed or investigational, or plans to receive a mAb outside of this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / 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.
|
One time 60-minute IV infusion of lyophilized placebo for 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.
|
One time 60-minute IV infusion of lyophilized placebo for 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.
|
One time 60-minute IV infusion of lyophilized placebo for 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.
|
One time 60-minute IV infusion of lyophilized placebo for 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.
|
One time 60-minute IV infusion of lyophilized placebo for SAR440894
One time 60-minute IV infusion of SAR440894 monoclonal antibody (IgG1) directed against the E2 envelope protein of chikungunya virus
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Occurrence of adverse events (AEs)
Time Frame: Day 1 through Day 150
|
Day 1 through Day 150
|
|
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.
|
Day 1 through Day 150
|
Occurrence of serious adverse events (SAEs)
Time Frame: Day 1 through Day 150
|
Day 1 through Day 150
|
|
Occurrence of clinically significant (CS) 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.
|
Day 1 through Day 150
|
Occurrence of clinically significant (CS) 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.
|
Day 1 through Day 150
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Day 1 through Day 150
|
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.
|
Day 1 through Day 150
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18-0006
- HHSN272201500006I
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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