First in Man Study to Evaluate Initial Safety
Conditions
Keywords
complement-mediated diseases
Brief summary
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).
Interventions
DRUGGL-0719
Administration route: intravenous infusion and subcutaneous injection
DRUGPlacebo
Administration route: intravenous infusion and subcutaneous injection
Sponsors
Gliknik Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| Incidence of anti-drug antibodies | Day -1, Day 15±1 and Follow-up (Day 31±2) |
| 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) |
| Time of the maximum observed concentration (tmax) | Day 1 to Follow-up (Day 31±2) |
| Maximum Observed Concentration (Cmax) | Day 1 to Follow-up (Day 31±2) |
| Apparent terminal elimination half-life (t1/2) | Day 1 to 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) |
Countries
United Kingdom
Contacts
CONTACTGliknik Clinical Trials Group
PRINCIPAL_INVESTIGATORJim Bush, MBChB, PhD
Fortrea Clinical Research Unit Ltd.
Outcome results
None listed