Safety Study of Dengushield in Healthy Adults

Study Overview
=================
Brief Summary
-----------------
This Phase 1 study to evaluate the safety of a single dose of Dengushield (dengue monoclonal antibody) in healthy adults.

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.

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

Conditions
-----------------
Phase 1, Dengue

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy adults aged 18-45 years, men, or women. Negative Dengue NS1 at screening indicating no current dengue infection Seronegative for dengue IgG Participants who are willing to comply with the requirements of the study protocol and attend scheduled visit. Participants who give written informed consent. Participants having laboratory parameters within normal range Participants with Body Mass Index (BMI) between 18 to 30 (both inclusive) Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations that is acceptable for study entry. Exclusion Criteria: 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 History or presence of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, autoimmune, dermatologic or immunosuppressive disorders. Evidence of any other significant active haematological disease, or having donated > 450 mL of blood within the past three months. Evidence or history of substance abuse including alcohol, or previous substance abuse within the last year. Participation or planned participation in a study involving the administration of an investigational compound within the past one month or during this study period. Planned administration of any vaccine not foreseen by the study protocol 4 weeks before and after dosing except for influenza vaccination. 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. Laboratory confirmed infection with hepatitis B virus (HBsAg positive), hepatitis C virus (anti-HCV positive) or human immunodeficiency virus (HIV positive) at screening. History of allergic disease, allergic reactions or known hypersensitivity to any component of the study product (Mild non-medication allergies allowed). Known bleeding disorders. Women who are pregnant, breast-feeding, or considering becoming pregnant. Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the participant.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase 1, randomized, partially-blind (observer-blind), placebo controlled, single dose ascending study in healthy adults. For the Cohort 1 (Initial Safety Cohort), no placebo control will be used and hence, blinding is not applicable. There will be 4 dose levels. The proposed doses to be studied are; 1 mg/kg, 3 mg/kg, 12 mg/kg and 25 mg/kg. Total of 40 participants will be dosed and followed till Day 84 from dosing.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (Initial Safety Cohort) 1 mg/kg<br>4 participants will be administered Dengushield at 1 mg/kg body weight as Intravenous injection. | Biological: Dengushield 1 mg/kg (Cohort 1) intravenous<br>* Participants will be administered Dengushield 1 mg/kg as slow intravenous injection.<br>|
| Experimental: Cohort 2 Experimental 3mg/kg<br>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<br>* Participants will be administered Dengushield 3 mg/kg as slow intravenous infusion.<br>|
| Placebo Comparator: Cohort 2 Placebo 3 mg/kg<br>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<br>* Participants will be administered Placebo 3 mg/kg as slow intravenous infusion.<br>|
| Experimental: Cohort 3 Experimental 7 mg/kg<br>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<br>* Participants will be administered Dengushield 7 mg/kg as slow intravenous infusion.<br>|
| Placebo Comparator: Cohort 3 Placebo 7 mg/kg<br>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<br>* Participants will be administered Placebo 7 mg/kg as slow intravenous infusion.<br>|
| Experimental: Cohort 4 Experimental 12 mg/kg<br>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<br>* Participants will be administered Dengushield 12 mg/kg as slow intravenous infusion.<br>|
| Placebo Comparator: Cohort 4 Placebo 12 mg/kg<br>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<br>* Participants will be administered Placebo 12 mg/kg as slow intravenous infusion.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dengue