Safety Study of Dengushield in Healthy Adults

A Phase I, Partially Blind (Observer-blind), Randomized, Single Dose Ascending Study of Dengue Monoclonal Antibody (Dengushield) in Healthy Adults

This Phase 1 study to evaluate the safety of a single dose of Dengushield (dengue monoclonal antibody) in healthy adults.

Study Overview

• Status: Completed
• Conditions: Dengue; Phase 1
• Intervention / Treatment: Biological: Dengushield 1 mg/kg (Cohort 1) intravenous; Biological: Dengushield 3 mg/kg (Cohort 2) intravenous; Biological: Placebo 3 mg/kg (Cohort 2) intravenous; Biological: Dengushield 7 mg/kg (Cohort 3) intravenous; Biological: Placebo 7 mg/kg (Cohort 3) intravenous; Biological: Dengushield 12 mg/kg (Cohort 4) intravenous; Biological: Placebo 12 mg/kg (Cohort 4) intravenous

Detailed Description

This Phase 1 study will evaluate the safety and tolerability of a single dose of Dengushield (dengue monoclonal antibody) in healthy adults in a dose-escalating study design. In addition, pharmacokinetics will also be studied.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • CMAX Clinical Research Pty Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy adults aged 18-45 years, men, or women.
2. Negative Dengue NS1 at screening indicating no current dengue infection
3. Seronegative for dengue IgG
4. Participants who are willing to comply with the requirements of the study protocol and attend scheduled visit.
5. Participants who give written informed consent.
6. Participants having laboratory parameters within normal range
7. Participants with Body Mass Index (BMI) between 18 to 30 (both inclusive)
8. Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations that is acceptable for study entry.

Exclusion Criteria:

1. Presence of acute infection in the preceding 14 days or presence of a temperature ≥ 38.0°C, or acute symptoms of infection greater than of "mild" severity on the scheduled date of first dosing
2. History or presence of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, autoimmune, dermatologic or immunosuppressive disorders.
3. Evidence of any other significant active haematological disease, or having donated > 450 mL of blood within the past three months.
4. Evidence or history of substance abuse including alcohol, or previous substance abuse within the last year.
5. Participation or planned participation in a study involving the administration of an investigational compound within the past one month or during this study period.
6. Planned administration of any vaccine not foreseen by the study protocol 4 weeks before and after dosing except for influenza vaccination.
7. Receipt of immunoglobulins and/or any blood products within 9 months of study enrolment or planned administration of any of these products during the study period.
8. Laboratory confirmed infection with hepatitis B virus (HBsAg positive), hepatitis C virus (anti-HCV positive) or human immunodeficiency virus (HIV positive) at screening.
9. History of allergic disease, allergic reactions or known hypersensitivity to any component of the study product (Mild non-medication allergies allowed).
10. Known bleeding disorders.
11. Women who are pregnant, breast-feeding, or considering becoming pregnant.
12. Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the participant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 (Initial Safety Cohort) 1 mg/kg; 4 participants will be administered Dengushield at 1 mg/kg body weight as Intravenous injection.	Biological: Dengushield 1 mg/kg (Cohort 1) intravenous; Participants will be administered Dengushield 1 mg/kg as slow intravenous injection.
Experimental: Cohort 2 Experimental 3mg/kg; Initially two participants will be randomized in 1:1 ratio to Dengushield or placebo as a sentinel cohort. If there are no causally related serious safety findings, remaining 10 participants for that cohort will be randomized in 9:1 ratio to Dengushield or placebo.	Biological: Dengushield 3 mg/kg (Cohort 2) intravenous; Participants will be administered Dengushield 3 mg/kg as slow intravenous infusion.
Placebo Comparator: Cohort 2 Placebo 3 mg/kg; Initially two participants will be randomized in 1:1 ratio to Dengushield or placebo as a sentinel cohort. If there are no causally related serious safety findings, remaining 10 participants for that cohort will be randomized in 9:1 ratio to Dengushield or placebo and enrolled.	Biological: Placebo 3 mg/kg (Cohort 2) intravenous; Participants will be administered Placebo 3 mg/kg as slow intravenous infusion.
Experimental: Cohort 3 Experimental 7 mg/kg; Initially two participants will be randomized in 1:1 ratio to Dengushield or placebo as a sentinel cohort. If there are no causally related serious safety findings, remaining 10 participants for that cohort will be randomized in 9:1 ratio to Dengushield or placebo.	Biological: Dengushield 7 mg/kg (Cohort 3) intravenous; Participants will be administered Dengushield 7 mg/kg as slow intravenous infusion.
Placebo Comparator: Cohort 3 Placebo 7 mg/kg; Initially two participants will be randomized in 1:1 ratio to Dengushield or placebo as a sentinel cohort. If there are no causally related serious safety findings, remaining 10 participants for that cohort will be randomized in 9:1 ratio to Dengushield or placebo.	Biological: Placebo 7 mg/kg (Cohort 3) intravenous; Participants will be administered Placebo 7 mg/kg as slow intravenous infusion.
Experimental: Cohort 4 Experimental 12 mg/kg; Initially two participants will be randomized in 1:1 ratio to Dengushield or placebo as a sentinel cohort. If there are no causally related serious safety findings, remaining 10 participants for that cohort will be randomized in 9:1 ratio to Dengushield or placebo.	Biological: Dengushield 12 mg/kg (Cohort 4) intravenous; Participants will be administered Dengushield 12 mg/kg as slow intravenous infusion.
Placebo Comparator: Cohort 4 Placebo 12 mg/kg; Initially two participants will be randomized in 1:1 ratio to Dengushield or placebo as a sentinel cohort. If there are no causally related serious safety findings, remaining 10 participants for that cohort will be randomized in 9:1 ratio to Dengushield or placebo.	Biological: Placebo 12 mg/kg (Cohort 4) intravenous; Participants will be administered Placebo 12 mg/kg as slow intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of participants with post-injection/ infusion adverse events (AEs) including hypersensitivity reaction, anaphylactic reaction and other AEs occurring within 4 hours of the start of dosing	Safety monitoring for 4 hours	4 hours post administration of drug
The proportion of participants with AEs, discontinuations due to AEs, and serious adverse events (SAEs)	Safety	84 days
Proportion of participants with clinically significant abnormal safety laboratory (hematology and chemistry parameters) findings	Safety	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to maximum serum concentration of Dengushield - Tmax	Time to maximum serum concentration of Dengushield - Tmax	84 days
Presence or absence of anti-Dengushield antibody in sera samples	Anti-Dengushield antibodies will be checked in sera samples.	84 days
Maximum serum concentration of dengushield - Cmax	Maximum serum concentration of dengushield	84 days
AUC from time 0 to infinity of Dengushield	Area under curve of Dengushield from time 0 to infinity (AUC0-infinity)	84 days
AUC from time 0 to 84 days of Dengushield	Area under curve of Dengushield from time 0 to 84 days (AUC0-84d)	84 days
Half life of Dengushield - t1/2	Half life of Dengushield	84 days
Volume of distribution of Dengushield	Volume of distribution of Dengushield	84 days
Clearance of dengushield	Clearance of dengushield	84 days
Elimination rate constant of dengushield	Elimination rate constant of dengushield	84 days

Collaborators and Investigators

• Sponsor: Serum Institute of India Pvt. Ltd.
• Collaborators: PPD

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2019
• Primary Completion (Actual): December 23, 2019
• Study Completion (Actual): December 23, 2019

Study Registration Dates

• First Submitted: March 16, 2019
• First Submitted That Met QC Criteria: March 19, 2019
• First Posted (Actual): March 21, 2019

Study Record Updates

• Last Update Posted (Actual): February 18, 2020
• Last Update Submitted That Met QC Criteria: February 15, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Dengue
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: Dengushield-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No