Phase 1 Study of SAR440894 vs Placebo

NCT04441905 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 18-0006
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

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 multiple sites. 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.

Conditions

Chikungunya Virus Infection

Keywords

Chikungunya Virus; dose escalation; healthy adults; Immunogenicity; Pharmacokinetics; phase 1; placebo; SAR440894

Outcome Measures

Primary Outcomes (8)

• Frequency of Adverse Events (AEs)

  The number of participants who experienced at least one unsolicited AE. An AE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered intervention-related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Any medical condition that was present at screening was considered a baseline finding and not reported as an AE. However, if the severity (i.e., grade) of any pre-existing medical condition increases, it was recorded as an AE. For participants who enrolled prior to protocol v11.0, AEs were assessed with protocol defined criteria. For participants who enrolled under protocol v11.0, AEs were assessed with NCI CTCAE, Version 5.0.

  Day 1 through Day 150

• Frequency of Serious Adverse Events (SAEs)

  The number of participants who experienced at least one SAE throughout the course of the study. An AE is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: * Death * A life-threatening adverse event * Inpatient hospitalization or prolongation of existing hospitalization * A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or * A congenital anomaly/birth defect.

  Day 1 through Day 150

• Frequency of Clinically Significant Vital Signs Results

  The number of participants who experienced at least one clinically significant vital signs abnormality post-dosing is summarized by parameter. Clinical significance was determined by the site investigator for all results that met toxicity grading criteria. For participants who enrolled prior to protocol v11.0, vital signs results were graded according to protocol-defined toxicity criteria. For participant who enrolled under protocol v11.0, vital signs results were graded according to the NCI CTCAE, Version 5.0.

  Day 1 through Day 150

• Frequency of Clinically Significant Chemistry Laboratory Results

  The number of participants who experienced at least one clinically significant chemistry laboratory abnormality post-dosing is summarized by parameter. Clinical significance was determined by the site investigator for all results that were outside the normal range. For participants who enrolled prior to protocol v11.0, laboratory results were graded according to protocol-defined toxicity criteria. For participants who enrolled under protocol v11.0, laboratory results were graded according to the NCI CTCAE, Version 5.0.

  Day 1 through Day 150

• Frequency of Clinically Significant Hematology Laboratory Results

  The number of participants who experienced at least one clinically significant hematology laboratory abnormality post-dosing is summarized by parameter. Clinical significance was determined by the site investigator for all results that were outside the normal range. For participants who enrolled prior to protocol v11.0, laboratory results were graded according to protocol-defined toxicity criteria. For participants who enrolled under protocol v11.0, laboratory results were graded according to the NCI CTCAE, Version 5.0.

  Day 1 through Day 150

• Frequency of Clinically Significant Coagulation Laboratory Results

  The number of participants who experienced at least one clinically significant coagulation laboratory abnormality post-dosing is summarized by parameter. Clinical significance was determined by the site investigator for all results that were outside the normal range. For participants who enrolled prior to protocol v11.0, laboratory results were graded according to protocol-defined toxicity criteria. For participants who enrolled under protocol v11.0, laboratory results were graded according to the NCI CTCAE, Version 5.0.

  Day 1 through Day 150

• Frequency of Clinically Significant Urinalysis Laboratory Results

  The number of participants who experienced at least one clinically significant urinalysis laboratory abnormality post-dosing is summarized by parameter. Clinical significance was determined by the site investigator for all results that were outside the normal range. For participants who enrolled prior to protocol v11.0, laboratory results were graded according to protocol-defined toxicity criteria. For participants who enrolled under protocol v11.0, laboratory results were graded according to the NCI CTCAE, Version 5.0.

  Day 1 through Day 150

• Frequency of Clinically Significant Electrocardiogram (ECG) Results

  The number of participants who experienced at least one clinically significant ECG result post-dosing. Clinical significance was determined by the site investigator.

  Day 1 through Day 150

Secondary Outcomes (11)

• Maximum Concentration (Cmax) of SAR440894 in Plasma

  Day 1 through Day 150

• Minimum Concentration (Cmin) of SAR440894 in Plasma

  Day 1 through Day 150

• Time of Maximum Concentration (Tmax) of SAR440894 in Plasma

  Day 1 through Day 150

• Time of Minimum Concentration (Tmin) of SAR440894 in Plasma

  Day 1 through Day 150

• Area Under the Concentration-Time Curve From 0 h (Pre-Dose) to the Lase Concentration Above the Lower Limit of Quantitation (AUC0-last) of SAR440894 in Plasma

  Day 1 through Day 150

Study Arms (5)

Cohort 1

EXPERIMENTAL

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; Biological: SAR440894

Cohort 2

EXPERIMENTAL

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; Biological: SAR440894

Cohort 3

EXPERIMENTAL

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; Biological: SAR440894

Cohort 4

EXPERIMENTAL

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; Biological: SAR440894

Cohort 5

EXPERIMENTAL

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; Biological: SAR440894

Interventions

Placebo OTHER

One time 60-minute IV infusion of lyophilized placebo for SAR440894

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

SAR440894 BIOLOGICAL

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

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Pharmaceutical Product Development - Orlando Clinical Research Unit

Orlando, Florida, 32806, United States

Location

Duke University School of Medicine - Duke Clinical Research Institute - Duke Clinical Research Unit

Durham, North Carolina, 27710, United States

Location

PPD - Austin Clinical Research Unit

Austin, Texas, 78744-1645, United States

Location

MeSH Terms

Conditions

Chikungunya Fever

Condition Hierarchy (Ancestors)

Alphavirus Infections; Arbovirus Infections; Vector Borne Diseases; Infections; Mosquito-Borne Diseases; Virus Diseases; Togaviridae Infections; RNA Virus Infections

Results Point of Contact

• Title: Kristie Miller, MD
• Organization: Pharmaceutical Product Development (PPD), part of Thermo Fisher Scientific

kristie.miller@ppd.com

512-747-1504

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2020
• First Posted: June 22, 2020
• Study Start: October 14, 2020
• Primary Completion: August 22, 2024
• Study Completion: August 22, 2024
• Last Updated: January 13, 2026
• Results First Posted: August 26, 2025

Record last verified: 2025-09-11

Locations

US (3)