Recombinant Hyperimmune Polyclonal Antibody (GIGA-2050) in COVID-19 Patients

A Phase 1 Single Ascending Dose Study of a Recombinant Hyperimmune Polyclonal Antibody Against SARS CoV-2 (GIGA-2050) in Patients Hospitalized With COVID-19

The purpose of this study is to evaluate the safety and tolerability of single ascending IV dose administrations of GIGA-2050 in patients hospitalized with COVID-19.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: GIGA-2050

Detailed Description

This is a Phase 1, first in human (FIH) study utilizing a 3+3 design to assess the safety and pharmacology of single ascending doses (SAD) of GIGA-2050 in patients hospitalized with confirmed COVID-19. Participants will receive a single intravenous (IV) infusion dose of GIGA-2050 and followed for safety, pharmacology and efficacy assessments during hospitalization, after discharge (if applicable), and through study discontinuation or end of study visit (Day 56).

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participant is ≥ 18 years of age.
• Positive result of a SARS CoV-2 RNA diagnostic test result ≤48 hours before enrollment, warranting hospital admission as per Investigator's judgement.
• COVID-19 pneumonia findings on imaging (chest X-ray or CT Scan).
• Requires oxygen supplementation with FIO2 approximately 30% or greater administered by nasal cannula, mask, or NIV.
• Participants can be on other medication on-label to treat COVID-19 respiratory disease that the Investigator deems clinically relevant in combination with the study drug, including corticosteroids. Passage of 24 hours after administration of the EUA drug will be required prior to dosing GIGA-2050.
• Men or non-lactating female participants who are surgically sterile or post-menopausal, or a Woman of Childbearing Potential (WCBP) with a negative pregnancy test at screening willing to use highly effective contraception methods.

Exclusion Criteria:

• Acute respiratory failure requiring invasive mechanical ventilation or ECMO at enrollment.
• Systolic Blood Pressure (SBP) <110 mmHg or heart rate >120 bpm.
• Pre-existing heart failure or unstable angina or myocardial infarction in the last month prior to screening.
• Pre-existing chronic respiratory condition(s).
• Evidence of acute kidney injury, increase of serum creatinine of ≥1.5 x baseline, or urine output of <0.5mL/kg/hr sustained for at least 6 hours once volume repleted.
• Aspartate aminotransferase (AST) ≥2.5 x ULN, alanine aminotransferase (ALT) ≥2.5 x ULN, and/or total bilirubin >1.5 x ULN, or severe hepatic impairment.
• Known systemic hypersensitivity to recombinant antibody therapies.
• Female participant who is pregnant.
• Participant is expected to transfer to a non-investigative facility from the investigation site and cannot be monitored for compliance with protocol-required safety monitoring procedures.
• Participants who are currently participating or have participated in another clinical trial within 30 days prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 mg GIGA-2050 per kg BW; Participants will receive a single IV infusion of 5 mg GIGA-2050 per kg BW	Drug: GIGA-2050; Recombinant Hyperimmune Polyclonal Antibody
Experimental: 15 mg GIGA-2050 per kg BW; Participants will receive a single IV infusion of 15 mg GIGA-2050 per kg BW, or as determined by SRC review	Drug: GIGA-2050; Recombinant Hyperimmune Polyclonal Antibody
Experimental: 50 mg GIGA-2050 per kg BW; Participants will receive a single IV infusion of 50 mg GIGA-2050 per kg BW, or as determined by SRC review	Drug: GIGA-2050; Recombinant Hyperimmune Polyclonal Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Frequency of TEAEs graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	Day 1 up to Day 56
Incidence of dose limiting toxicities (DLTs)	Frequency of DLTs at each dose level	Day 1 up to Day 3
Change from baseline of vital signs, physical examination, and clinical laboratory assessments	Numeric summaries of all observed findings and changes for vital signs, laboratory assessments, physical examinations, and ECG	Day 1 up to Day 56
Incidence of infusion-related reactions (IRR) and hypersensitivity reactions	Frequency of IRR and hypersensitivity reactions	Day 1 through Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacological evaluation of single doses of GIGA-2050	Serum titers of antibodies directed against SARS CoV-2 will be measured for the pharmacological profile of single doses of GIGA-2050	Day 1 up to Day 28

Collaborators and Investigators

• Sponsor: GigaGen, Inc.
• Investigators: Principal Investigator: Sean Liu, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Keating SM, Mizrahi RA, Adams MS, Asensio MA, Benzie E, Carter KP, Chiang Y, Edgar RC, Gautam BK, Gras A, Leong J, Leong R, Lim YW, Manickam VA, Medina-Cucurella AV, Niedecken AR, Saini J, Simons JF, Spindler MJ, Stadtmiller K, Tinsley B, Wagner EK, Wayham N, Tracy L, Lundberg CV, Buscher D, Terencio JV, Roalfe L, Pearce E, Richardson H, Goldblatt D, Ramjag AT, Carrington CVF, Simmons G, Muench MO, Chamow SM, Monroe B, Olson C, Oguin TH, Lynch H, Jeanfreau R, Mosher RA, Walch MJ, Bartley CR, Ross CA, Meyer EH, Adler AS, Johnson DS. Generation of recombinant hyperimmune globulins from diverse B-cell repertoires. Nat Biotechnol. 2021 Aug;39(8):989-999. doi: 10.1038/s41587-021-00894-8. Epub 2021 Apr 15.

Study record dates

Study Major Dates

• Study Start (Actual): May 24, 2021
• Primary Completion (Actual): January 11, 2022
• Study Completion (Actual): January 11, 2022

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 12, 2021

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; SARS CoV-2
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: GG-GIGA-2050-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No current plan to share IPD due to evaluation of potential DLTs.

Drug and device information, study documents

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