Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects

• ClinicalTrials.gov Identifier: NCT05318534
• Recruitment Status: Recruiting
• First Posted: April 8, 2022
• Last Update Posted: September 10, 2022
• Sponsor: Gliknik Inc.
• Information provided by (Responsible Party): Gliknik Inc.

Study Description

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) doses in healthy adult male and female subjects.

Condition or disease	Intervention/treatment	Phase
First in Man Study to Evaluate Initial Safety	Drug: GL-0719; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: GL-0719 - A Phase 1, Double-blind, Placebo-controlled, Single Ascending Intravenous Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study in Healthy Male and Female Subjects
• Actual Study Start Date: April 8, 2022
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
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. Cohort 1: 4 subjects Cohort 2: 8 subjects Cohort 3: 8 subjects Cohort 4: 8 subjects Cohort 5: 8 subjects	Drug: GL-0719; Administration route: intravenous infusion
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. Cohort 1: 4 subjects Cohort 2: 8 subjects Cohort 3: 8 subjects Cohort 4: 8 subjects Cohort 5: 8 subjects	Drug: Placebo; Administration route: intravenous infusion

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Area Under the Concentration time Curve from Time 0 Extrapolated to Infinity (AUC0-∞) [ Time Frame: Day 1 to Follow-up (Day 31±2) ]
2. Area Under the Concentration time Curve from Time 0 to the Time of the Last (AUC0-tlast) [ Time Frame: Day 1 to Follow-up (Day 31±2) ]
3. Maximum Observed Concentration (Cmax) [ Time Frame: Day 1 to Follow-up (Day 31±2) ]
4. Time of the maximum observed concentration (tmax) [ Time Frame: Day 1 to Follow-up (Day 31±2) ]
5. Apparent terminal elimination half-life (t1/2) [ Time Frame: Day 1 to Follow-up (Day 31±2) ]
6. The degree of complement classical pathway inhibition in study subjects over time as evaluated by the MicroVue CH50 Eq EIA assay [ Time Frame: Day 1 to Follow-up (Day 31±2) ]
7. Incidence of anti-drug antibodies [ Time Frame: Day -1, Day 15±1 and Follow-up (Day 31±2) ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

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.
6. 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.

Exclusion Criteria:

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.
6. Concurrent medical condition requiring the chronic concurrent use of systemic steroids or immunosuppressants.

7. Subjects with ANY of the following abnormalities in clinical laboratory tests at screening or on admission, as assessed by the study-specific laboratory and confirmed by a single repeat tests, if deemed necessary:

   • Aspartate aminotransferase or alanine aminotransferase level >1.25 × upper limit of normal (ULN).
   • Total bilirubin level > ULN; subjects with a history of Gilberts syndrome will not be eligible for the study.
   • Serum creatinine levels > ULN.
   • Estimated glomerular filtration rate of < 80 mL/min/1.73m^2 (screening only) calculated using the Modification of Diet in Renal Disease (MDRD) equation.
8. Any history of thromboembolic events or coagulopathy.
9. Diagnosis of a malignancy except for adequately treated and cured 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.
10. Active infection or other immunocompromising condition requiring IV treatment within 28 days of study treatment on Day 1.
11. Prior splenectomy or organ allograft.

Other protocol defined inclusion/exclusion criteria may apply.

Contacts and Locations

Contacts

Contact: Jeffrey M. Herpst, RN, OCN; 410-665-0662; jherpst@gliknik.com

Locations

United Kingdom

Labcorp Clinical Research Unit Ltd; Recruiting

Leeds, United Kingdom, LS2 9LH

Principal Investigator: Jim Bush, MBChB, PhD

Sponsors and Collaborators

Gliknik Inc.

Investigators

• Principal Investigator: Jim Bush, MBChB, PhD; Labcorp Clinical Research Unit Ltd.

More Information

• Responsible Party: Gliknik Inc.
• ClinicalTrials.gov Identifier: NCT05318534
• Other Study ID Numbers: GL0719-01; 2021-004925-57 ( EudraCT Number )
• First Posted: April 8, 2022
• Last Update Posted: September 10, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gliknik Inc.:

complement-mediated diseases