Back to results

Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in ZIKV Infected Patients

Primary Purpose

Treatment of Acute Zika Virus Infection

Status

Withdrawn

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

Tyzivumab

Placebo

About this trial

This is an interventional treatment trial for Treatment of Acute Zika Virus Infection

Eligibility Criteria

21 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Adult volunteers, aged 21 to 60, men or women
a. Women must fulfil one (1) of the following criteria: i. Post-menopausal; either amenorrhea ≥ 12 months or follicle stimulating hormone > 40 mIU/mL ii. Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation iii. Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening day until 100 days post-infusion b. Male subjects who are non-vasectomized (or vasectomized less than six (6) months prior to dosing) and have female partners of childbearing potential must be willing to use an effective birth control method when having heterosexual intercourse, from screening day until 100 days post-infusion
Any one or a combination of symptoms and signs suggestive of ZIKV acute infection, presenting within 48 hours from onset
Positive ZIKV PCR for acute ZIKV infection
Subjects who are willing to comply with the requirements of the study protocol and attend scheduled visit
Subjects who give written informed consent approved by the Ethical Review Board governing the site
Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations that are acceptable for study entry
Accessible vein in the forearm for blood collection

Exclusion Criteria:

History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders
Evidence of clinically significant anaemia (HB < 10 g/dL) or any other significant active haematological disease, or having donated > 450 mL of blood within the past three (3) months
Evidence of substance abuse, or previous substance abuse
Participation or planned participation in a study involving the administration of an investigational compound within the past four (4) months or during this study period
Planned administration of any vaccine not foreseen by the study protocol 12 weeks before first dosing day and up to four (4) months after dosing
Receipt of immunoglobulins and/or any blood products within nine (9) months of study enrolment or planned administration of any of these products during the study period
History of any reaction to monoclonal antibodies
Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception
Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the subject

Sites / Locations

SingHealth Investigational Medicine Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm Type

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

2 mg/kg

2 mg/kg - Placebo

5 mg/kg

5 mg/kg - Placebo

10 mg/kg

10 mg/kg - Placebo

20 mg/kg

20 mg/kg - Placebo

Arm Description

Subject will be administered with 2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Subject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Subject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Subject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability)

Presence or absence of infusion reaction (hypersensitivity / anaphylaxis / etc.) in dose cohorts.

Secondary Outcome Measures

Viral Clearance Post-Tyzivumab Infusion (Efficacy)

Time taken to achieve ZIKV clearance (CL) from blood via negative virus isolation in subjects acutely infected with ZIKV when given an IV infusion of Tyzivumab

Full Information

NCT ID

NCT03776695

First Posted

December 12, 2018

Last Updated

March 8, 2022

Sponsor

Tychan Pte Ltd.

Collaborators

Singapore Clinical Research Institute, Duke-NUS Graduate Medical School

1. Study Identification

Unique Protocol Identification Number

NCT03776695

Brief Title

Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in ZIKV Infected Patients

Official Title

Phase 1 Time Lagged, Parallel-Group, Randomized, Placebo-Controlled, Single-Blind, Single Ascending Dose Study of Tyzivumab in ZIKV Infected Patients

Study Type

Interventional

2. Study Status

Record Verification Date

March 2022

Overall Recruitment Status

Withdrawn

Why Stopped

Lack of Zika infected patients

Study Start Date

October 9, 2018 (Actual)

Primary Completion Date

January 5, 2022 (Actual)

Study Completion Date

January 5, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tychan Pte Ltd.

Collaborators

Singapore Clinical Research Institute, Duke-NUS Graduate Medical School

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Zika virus (ZIKV) infection is a new emerging arbovirus disease, caused by the same vector that transmits Dengue virus, Aedes aegypti. ZIKV is a growing public health problem, rapidly spreading throughout the continents since the first epidemic was reported in the French Polynesian islands. Currently, there are several ZIKV vaccine candidates in clinical trials. However, no ZIKV therapy (biologic or small molecule) has advanced to clinical trials. Tyzivumab will be the first therapeutic in the world, specifically targeting ZIKV, to enter clinical trials. This is a Phase 1, time-lagged, parallel-group, randomized, placebo-controlled, single-blind, single ascending dose, Tyzivumab, ZIKV monoclonal antibody (mAb), study to be conducted in ZIKV polymerase chain reaction (PCR) positive patients. Tyzivumab will be administered once through single IV infusion over 30 minutes. Total duration of study participation is estimated at approximately 85 days from the date of screening. Post-trial monitoring through weekly telephone calls will continue from Day 85 post-dose onwards for another three (3) more months. The main objective of this study is to evaluate the safety of Tyzivumab in acutely infected adult patients. Assessment of time taken to achieve negative ZIKV isolation from acute ZIKV infected subjects' blood will be the study's secondary objectives.

Detailed Description

Dose escalation in this study will include 28 ZIKV-infected patients in four (4) dose cohorts. Eligible subjects will be enrolled into dose cohorts of seven (7) subjects each. Within each dose cohort, subjects will be randomized to either Tyzivumab or Placebo Groups, with five (5) subjects receiving Tyzivumab and two (2) receiving Placebo per cohort. There will be up to four (4) dose levels / cohorts, for a total of 28 subjects. The proposed doses to be studied are 2, 5, 10, and 20 mg/kg. Within each dose cohort, a minimum of 48-hour interval is required between Tyzivumab dosing of subject 1 and 2 and between subject 2 and 3, and a minimum of 24-hour interval is required between Tyzivumab dosing of subject 3 and 4 and between subject 4 and 5. No such time interval will be required for the Placebo dosing of subjects (i.e. a Placebo subject can be dosed concurrently with or immediately after a Tyzivumab treatment subject). Dosing of the last dose cohort (20 mg/kg) is optional if a trend of reduction in viral load and viral isolation has been observed in dose level 1 (2 mg/kg), 2 (5 mg/kg) or 3 (10 mg/kg). Dose escalations will be guided by review of clinical signs, adverse events (AEs), and laboratory tests (including viral titre data) of the prior group (up to Day 7 after dosing) by a safety monitoring committee. Safety analysis (up to Day 7) will also be completed for the equivalent dose of ZKT-001 prior to the commencement of dosing in ZKT-002 for each specified dose. PD, PK and ADA measurements will be conducted at various time points throughout the study. Subjects will be followed for up to approximately Day 84 safety and tolerability assessment. Serum samples for PD, PK and ADA assessments, and urine samples for PD assessments will be taken at specified time points.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Treatment of Acute Zika Virus Infection

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

Participant

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

2 mg/kg

Arm Type

Experimental

Arm Description

Subject will be administered with 2 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Arm Title

2 mg/kg - Placebo

Arm Type

Placebo Comparator

Arm Description

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Arm Title

5 mg/kg

Arm Type

Experimental

Arm Description

Subject will be administered with 5 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Arm Title

5 mg/kg - Placebo

Arm Type

Placebo Comparator

Arm Description

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Arm Title

10 mg/kg

Arm Type

Experimental

Arm Description

Subject will be administered with 10 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Arm Title

10 mg/kg - Placebo

Arm Type

Placebo Comparator

Arm Description

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Arm Title

20 mg/kg

Arm Type

Experimental

Arm Description

Subject will be administered with 20 mg/kg of Tyzivumab via IV infusion over a period of 30 minutes.

Arm Title

20 mg/kg - Placebo

Arm Type

Placebo Comparator

Arm Description

Subject will be administered with 0.9% saline via IV infusion over a period of 30 minutes.

Intervention Type

Biological

Intervention Name(s)

Tyzivumab

Intervention Description

Tyzivumab Injection, (100 mg/5 mL/Vial), Zika Virus (ZIKV) Monoclonal Antibody (mAb)

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

0.9% Saline

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Event (Safety and Tolerability)

Description

Presence or absence of infusion reaction (hypersensitivity / anaphylaxis / etc.) in dose cohorts.

Time Frame

84 Days

Secondary Outcome Measure Information:

Title

Viral Clearance Post-Tyzivumab Infusion (Efficacy)

Description

Time taken to achieve ZIKV clearance (CL) from blood via negative virus isolation in subjects acutely infected with ZIKV when given an IV infusion of Tyzivumab

Time Frame

84 Days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adult volunteers, aged 21 to 60, men or women a. Women must fulfil one (1) of the following criteria: i. Post-menopausal; either amenorrhea ≥ 12 months or follicle stimulating hormone > 40 mIU/mL ii. Surgically sterile; hysterectomy, bilateral oophorectomy, or tubal ligation iii. Women of childbearing potential participating in heterosexual sexual relations must be willing to use adequate contraception from screening day until 100 days post-infusion b. Male subjects who are non-vasectomized (or vasectomized less than six (6) months prior to dosing) and have female partners of childbearing potential must be willing to use an effective birth control method when having heterosexual intercourse, from screening day until 100 days post-infusion Any one or a combination of symptoms and signs suggestive of ZIKV acute infection, presenting within 48 hours from onset Positive ZIKV PCR for acute ZIKV infection Subjects who are willing to comply with the requirements of the study protocol and attend scheduled visit Subjects who give written informed consent approved by the Ethical Review Board governing the site Satisfactory baseline medical assessment as assessed by physical examination and normal laboratory values or minor variations that are acceptable for study entry Accessible vein in the forearm for blood collection Exclusion Criteria: History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders Evidence of clinically significant anaemia (HB < 10 g/dL) or any other significant active haematological disease, or having donated > 450 mL of blood within the past three (3) months Evidence of substance abuse, or previous substance abuse Participation or planned participation in a study involving the administration of an investigational compound within the past four (4) months or during this study period Planned administration of any vaccine not foreseen by the study protocol 12 weeks before first dosing day and up to four (4) months after dosing Receipt of immunoglobulins and/or any blood products within nine (9) months of study enrolment or planned administration of any of these products during the study period History of any reaction to monoclonal antibodies Pregnant or lactating women, or women of childbearing potential who are unwilling to use adequate contraception Any condition that, in the opinion of the investigator, would complicate or compromise the study or well-being of the subject

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jenny Low, MBBS

Organizational Affiliation

Singapore General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

SingHealth Investigational Medicine Unit

City

Singapore

ZIP/Postal Code

169608

Country

Singapore

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Safety and Tolerability of an Antibody Against Zika Virus (Tyzivumab) in ZIKV Infected Patients

We'll reach out to this number within 24 hrs