Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects and Safety, Tolerability, Pharmacokinetics, and Pilot Efficacy Biomarkers in Subjects With Cold Agglutinin Disease

GL-0719 - A Phase 1, Double-blind, Placebo-controlled, Single Ascending Intravenous and Subcutaneous Injection Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects and an Open-label Evaluation of Safety, Tolerability, Pharmacokinetics, and Pilot Efficacy Biomarkers in Subjects With Cold Agglutinin Disease

The purpose of this first-in-human (FIH) study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GL-0719 following single intravenous (IV) and subcutaneous injection (SC) doses in healthy adult male and female subjects.

In addition, safety, tolerability, PK, and pilot efficacy biomarkers will be evaluated in subjects with cold agglutinin disease (CAD).

Study Overview

• Status: Recruiting
• Conditions: First in Man Study to Evaluate Initial Safety
• Intervention / Treatment: Drug: GL-0719; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gliknik Clinical Trials Group; Phone Number: 410-665-0662; Email: gliknikclinicaltrialinquiries@gliknik.com

Study Locations

• United Kingdom
  • Leeds, United Kingdom, LS2 9LH
    • Recruiting
    • Fortrea Clinical Research Unit Ltd
    • Principal Investigator: Jim Bush, MBChB, PhD
    • Contact: Jim Bush, MBChB, PhD; Phone Number: 01133013500

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Cohorts 1 to 7

1. Healthy female or male subjects who, at the time of screening, are between the ages of 18 and 65 years, inclusive.
2. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
3. Body mass index of 18.0 to 32.0 kg/m^2, inclusive; and a total body weight > 50 kg up to a maximum of 110 kg.
4. Study subjects must have received a quadrivalent meningococcal conjugate vaccine (meningococcal serogroups A, C, W, and Y) within the past 5 years or vaccination a minimum of 14 days prior to initial study drug administration.
5. The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent.

Inclusion Criteria for Cohorts 8 to 9

1. Female or male subjects who, at the time of screening, are at least 18 years of age with a total body weight of ≥ 50 kg.
2. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception.
3. The subject must be capable of understanding the investigational nature, potential risks and benefits of the study and capable of providing valid informed consent.
4. The subject must be willing to return to the study center for study treatment and study-related follow-up procedures as required by the protocol.
5. Study subjects must have received a quadrivalent meningococcal conjugate vaccine (meningococcal serogroups A, C, W, and Y) within the past 5 years or vaccination a minimum of 14 days prior to initial study drug administration.
6. The Participant Identification Center (PIC) site will have provided evidence that the PIC site used to confirm diagnosis of Cold Agglutinin Disease (CAD)
7. Primary Cold Agglutinin Disease (CAD) or CAD secondary to active lymphoid or other hematologic malignancy (Cold Agglutinin Syndrome).
8. Hemoglobin level < 105 gram per liter (g/L).
9. Bilirubin level above the normal reference range.

Key Exclusion Criteria for Cohorts 1 to 7

1. History of any clinically significant (as determined by the investigator) cardiac, endocrine, hematological, hepatic, immunological, metabolic, urological, pulmonary, neurological, dermatological, psychiatric, renal, or other major disease.
2. Evidence of clinically significant medical condition or other condition that might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study.
3. Signs and symptoms of, or diagnosis consistent with a chronic autoimmune disorder and/or positive antinuclear antibodies (ANA) test by indirect immunofluorescence confirmed by ANA titer ≥ 1:160.
4. Documented history of autoimmune disease, or history of a syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy.
5. Any underlying medical condition that, in the opinion of the investigator, renders the subject a poor candidate for this study or could confound the results of the study or put the subject at undue risk.

Key Exclusion Criteria for Cohorts 8 to 9

1. CAD secondary to infection or an autoimmune disorder.
2. CAD secondary to active lymphoid or other hematologic malignancy not meeting the inclusion criteria.
3. Diagnosis of any other malignancy except for adequately treated basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the subject has been disease-free for ≥ 5 years.
4. Clinically relevant infection of any kind within the month preceding enrollment (example, active hepatitis C, pneumonia).
5. Clinical diagnosis of Systemic Lupus Erythematosus (SLE), other autoimmune disorders, or ANA titer > 1:160 at Screening.
6. Positive hepatitis panel and/or positive HIV (Human Immuno Deficiency) test. Subjects whose results are compatible with prior immunization may be included at the discretion of the investigator.
7. Positive HIV antibody at Screening.
8. Treatment with an investigational drug within 90 days or five half-lives preceding the first dose of IP (whichever is longer), with the exception of subjects who received GL-0719 in this study in Cohort 8, who cannot be re-enrolled in Cohort 9 within 60 days after their last dose of GL-0719.
9. Concurrent plasma exchange therapy.

Other protocol defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Dose level cohorts randomized in a 3:1 ratio to GL-0719 or placebo treatment, respectively. The study will comprise a single-dose, sequential-group design. Single Ascending IV Dose Cohorts; Cohort 1: 4 subjects; Cohort 2: 8 subjects; Cohort 3: 8 subjects; Cohort 4: 8 subjects; Cohort 5: 8 subjects Subcutaneous Injection Cohort; Cohort 6: 8 subjects; Cohort 7: 8 subjects	Drug: Placebo; Administration route: intravenous infusion and subcutaneous injection
Experimental: GL-0719; Dose level cohorts randomized in a 3:1 ratio to GL-0719 or placebo treatment, respectively. The study will comprise a single-dose, sequential-group design. Single Ascending IV Dose Cohorts; Cohort 1: 4 subjects; Cohort 2: 8 subjects; Cohort 3: 8 subjects; Cohort 4: 8 subjects; Cohort 5: 8 subjects Subcutaneous Injection Cohort; Cohort 6: 8 subjects; Cohort 7: 8 subjects; Cohort 8 (Patient Arm): Up to 6 subjects with Cold Agglutinin Disease (CAD); Placebo is not applicable.; Cohort 9 (Patient Arm): Up to 12 subjects with Cold Agglutinin Disease (CAD); Placebo is not applicable.	Drug: GL-0719; Administration route: intravenous infusion and subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of adverse events (AEs)	Day 1 to Follow-up (Day 31±2)
Incidence of laboratory abnormalities, based on hematology, clinical chemistry, and urinalysis test results	Screening (Days -42 to -15) to Follow-up (Day 31±2)
Incidence of abnormal clinical laboratory findings in 12-lead ECG parameters, vital signs, physical examination and measurement of cytokines	Screening (Days -42 to -15) to Follow-up (Day 31±2)

Secondary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration time Curve from Time 0 Extrapolated to Infinity (AUC0-∞)	Day 1 to Follow-up (Day 31±2)
Area Under the Concentration time Curve from Time 0 to the Time of the Last (AUC0-tlast)	Day 1 to Follow-up (Day 31±2)
Maximum Observed Concentration (Cmax)	Day 1 to Follow-up (Day 31±2)
Time of the maximum observed concentration (tmax)	Day 1 to Follow-up (Day 31±2)
Apparent terminal elimination half-life (t1/2)	Day 1 to Follow-up (Day 31±2)
Incidence of anti-drug antibodies	Day -1, Day 15±1 and Follow-up (Day 31±2)
The degree of complement classical pathway inhibition in study subjects over time	Day 1 to Follow-up (Day 31±2)

Collaborators and Investigators

• Sponsor: Gliknik Inc.
• Investigators: Principal Investigator: Jim Bush, MBChB, PhD, Fortrea Clinical Research Unit Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: March 28, 2022
• First Submitted That Met QC Criteria: April 7, 2022
• First Posted (Actual): April 8, 2022

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: complement-mediated diseases
• Additional Relevant MeSH Terms: Autoimmune Diseases; Immune System Diseases; Hematologic Diseases; Anemia, Hemolytic; Anemia; Anemia, Hemolytic, Autoimmune
• Other Study ID Numbers: GL0719-01; 2021-004925-57 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No