Safety Study of Dengushield in Healthy Adults

Phase 1

Completed

• Conditions: Dengue; Phase 1
• Interventions: Biological: Dengushield 7 mg/kg (Cohort 3) intravenous; Biological: Placebo 7 mg/kg (Cohort 3) intravenous; Biological: Placebo 12 mg/kg (Cohort 4) intravenous; 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 12 mg/kg (Cohort 4) intravenous

• Registration Number: NCT03883620
• Lead Sponsor: Serum Institute of India Pvt. Ltd.

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.

Study Timeline

• Study First Submitted: 2019-03-16
• Study First Submitted QC: 2019-03-19
• Study First Posted: 2019-03-21
• Study Start: 2019-03-22
• Primary Completion: 2019-12-23
• Study Completion: 2019-12-23
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-15
• Last Update Posted: 2020-02-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 3 Experimental 7 mg/kg	Dengushield 7 mg/kg (Cohort 3) intravenous	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.
Cohort 3 Placebo 7 mg/kg	Placebo 7 mg/kg (Cohort 3) intravenous	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.
Cohort 4 Placebo 12 mg/kg	Placebo 12 mg/kg (Cohort 4) intravenous	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.
Cohort 1 (Initial Safety Cohort) 1 mg/kg	Dengushield 1 mg/kg (Cohort 1) intravenous	4 participants will be administered Dengushield at 1 mg/kg body weight as Intravenous injection.
Cohort 2 Experimental 3mg/kg	Dengushield 3 mg/kg (Cohort 2) intravenous	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.
Cohort 2 Placebo 3 mg/kg	Placebo 3 mg/kg (Cohort 2) intravenous	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.
Cohort 4 Experimental 12 mg/kg	Dengushield 12 mg/kg (Cohort 4) intravenous	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.

Primary Outcome Measures

Name	Time	Method
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	4 hours post administration of drug	Safety monitoring for 4 hours
The proportion of participants with AEs, discontinuations due to AEs, and serious adverse events (SAEs)	84 days	Safety
Proportion of participants with clinically significant abnormal safety laboratory (hematology and chemistry parameters) findings	28 days	Safety

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CMAX Clinical Research Pty Ltd; 🇦🇺 Adelaide, South Australia, Australia