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

Gliknik

Status and phase: Enrolling; Phase 1

Conditions: First in Man Study to Evaluate Initial Safety

Treatments: Drug: Placebo; Drug: GL-0719

Study type: Interventional

Funder types: Industry

Identifiers

NCT05318534

GL0719-01

2021-004925-57 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 57 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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 Cohort 8

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.

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.

Exclusion Criteria for Cohort 8

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.

Other protocol defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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57 participants in 2 patient groups, including a placebo group

GL-0719

Experimental group

Description:

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.

Treatment:

Drug: GL-0719

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo