Safety Study of CD24Fc When Administered Intravenously in Healthy Adult Subjects

A Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of CD24Fc When Administered Intravenously in Healthy Adult Subjects

Patrocinadores

Patrocinador principal: OncoImmune, Inc.

Colaborador: National Institute of Neurological Disorders and Stroke (NINDS)

Fuente OncoImmune, Inc.
Resumen breve

The purpose of this study is to evaluate the safety and tolerability of single ascending intravenous (IV) doses of CD24Fc in healthy adult subjects.

Descripción detallada

This was a Phase I, randomized, double-blind, placebo-controlled, single ascending dose study to assess the safety, tolerability, and PK of CD24Fc in healthy male and female adult subjects.

The population for this study was healthy males and females between the ages of 18 and 55 years, inclusive, with a body mass index between 18 kg/m2 and 30 kg/m2, inclusive.

A total of 40 subjects were enrolled in this study, in 5 cohorts of 8 subjects each. Six of the 8 subjects in each cohort received study drug and 2 subjects received placebo (0.9% sodium chloride, saline). The first cohort was dosed with 10 mg. Succeeding cohorts received 30 mg, 60 mg, 120 mg, and 240 mg of CD24Fc or matching placebo and were dosed at least 3 weeks apart to allow for review of safety and tolerability data for each prior cohort. Administration of the next higher dose to a new cohort of subjects was permitted only if adequate safety and tolerability had been demonstrated.

In each cohort, the initial 2 subjects were 1 study drug recipient and 1 placebo recipient on Day 1 (sentinel subjects). Subjects 3 to 5 and 6 to 8 were dosed after Day 7 (a minimum of 24 hours apart between the subgroups). Each subject was dosed at least 1 hour apart in the same subgroup. If necessary, dosing of the rest of the subjects was delayed pending review of any significant safety issues that may have arisen during the post-dose period involving the first or second subgroups in that cohort. The subsequent cohort was dosed at least 3 weeks after the prior cohort.

The total study duration for each subject was up to 63 days. Single dose administration occurred on Day 1.

The Screening Visit (Visit 1) occurred up to 21 days prior to the beginning of the active treatment period. After providing informed consent, subjects underwent screening procedures for eligibility.

Subjects were admitted to the Clinical Pharmacology Unit (CPU) on Day -1 (Visit 2), and the randomized treatment period began on Day 1 following a 10-hour minimum overnight fast. Subjects were randomly assigned to treatment with CD24Fc or placebo as a single dose. Subjects remained confined until the morning of Day 4.

All subjects returned to the CPU on Day 7, Day 14, Day 21, Day 28, and Day 42 (±1 day) for follow-up visits (Visit 3, Visit 4, Visit 5, Visit 6, and Visit 7). Visit 7 was the final visit for all subjects.

The assessment of safety was based primarily on the frequency of adverse events, clinical laboratory assessments (chemistry, hematology, and urinalysis), physical examinations, vital signs, 12-lead electrocardiograms (ECGs), and continuous telemetry monitoring. The Intent-to-Treat (ITT) Population was used for all summaries.

PK parameters were calculated using actual collection times. The following PK parameters for CD24Fc were calculated from the individual plasma concentrations profile by non compartmental approaches.

The PK Evaluable Population was defined as all subjects in the ITT Population who had evaluable concentration-time profiles for CD24Fc. The PK Evaluable Population was the population used for all PK analyses.

The PK listing, summary, and analysis were performed based on the plasma concentration of CD24Fc by treatment. Pharmacokinetic parameters were calculated using actual collection times. The PK parameters for CD24Fc (Cmax, Tmax, kel, t½, AUC0-42d, AUC0-inf, AUCextr, CL, and Vd) were calculated from the individual plasma concentrations profile by non-compartmental approaches.

The concentration of CD24Fc was summarized descriptively at each nominal time point by treatment (e.g., n, mean, standard deviation [SD], coefficient of variation [CV%], standard error, median, minimum, and maximum). Mean concentration (±SD) was plotted on a linear scale against nominal time points by treatment. Geometric mean concentration was plotted on a semi-logarithmic scale against nominal time points. The PK Evaluable Population was used for the summary and individual concentrations.

Individual concentration-time curves for CD24Fc were plotted on both a linear and semi-logarithmic scale against actual sampling times by subject.

Pharmacokinetic parameters were summarized for the PK Evaluable Population. All parameters were summarized by treatment with the number of observations, mean, SD, CV%, standard error, median, maximum, and minimum. Geometric mean and geometric CV% were also provided for the summary of AUCs and Cmax.

Dose proportionality of CD24Fc plasma PK parameters (AUCs and Cmax) was assessed using the power model: y = a DoseB, where y denotes the PK parameter being analyzed and a depends on subject. Dose proportionality implies that B = 1 and was assessed by estimated β along with its 90% confidence interval (CI). The exponent, B, in the power model was estimated by regressing the log-transformed PK parameter on log-transformed dose.

The power model was fitted by restricted maximum likelihood using SAS Proc Mixed. Both the intercept and slope were fitted as fixed effects. The mean slope was estimated from the power model and the corresponding 90% CI calculated.

The ITT Population consisted of all subjects who received at least 1 dose of the study drug. The ITT Population was the primary analysis population for subject information and safety evaluation.

The assessment of safety was based primarily on the frequency and nature of adverse events, clinical laboratory assessments (chemistry, hematology, and urinalysis), physical examinations, vital signs, 12-lead ECGs, and telemetry monitoring. The ITT Population was used for all summaries.

All adverse events were summarized by system organ class, preferred term, and treatment. A list of subjects who had serious adverse events (SAEs) and who discontinued from the study due to an adverse event was provided. The number and percentage of subjects who experienced at least 1 treatment-emergent adverse event (TEAE) were presented for each system organ class and for each preferred term by treatment. Treatment-emergent adverse events that were considered by the Investigator to be related to study drug were summarized in the same manner. Serious adverse events and adverse events leading to discontinuation from the study were listed separately.

Clinical laboratory evaluations (chemistry, hematology, and urinalysis) were summarized by treatment and visit. Change from baseline was also summarized. Vital signs (blood pressure, heart rate, respiratory rate, and temperature) were summarized by treatment and time point. Change from baseline was also summarized. All physical examination data were listed. Electrocardiogram parameters and the change from baseline were summarized. Overall interpretations were listed.

Estado general Completed
Fecha de inicio February 2014
Fecha de Terminación December 2016
Fecha de finalización primaria January 2015
Fase Phase 1
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Assessment of Safety Based Primarily on the Frequency and Nature of Adverse Events, Clinical Laboratory Assessments (Chemistry, Hematology, and Urinalysis), Physical Examinations, Vital Signs, 12-lead ECGs, and Telemetry Monitoring. 42 days after treatment
Resultado secundario
Medida Periodo de tiempo
Pharmacokinetics of Drug. 42 days after treatment
Pharmacokinetics of Drug Cmax. 42 days after treatment.
Pharmacokinetics of AUC 42 days after treatment.
Determine Plasma Drug Half Life. 42 days
Inscripción 40
Condición
Intervención

Tipo de intervención: Biological

Nombre de intervención: CD24Fc

Descripción: Recombinant fusion protein consisting of the extracellular domain of mature human CD24 linked to the human immunoglobulin G1 (IgG1) Fc domain

Etiqueta de grupo de brazo: CD24Fc

Otro nombre: CD24IgG

Tipo de intervención: Drug

Nombre de intervención: Saline

Descripción: 0.9% sodium chloride

Etiqueta de grupo de brazo: Saline

Otro nombre: Normal saline

Elegibilidad

Criterios:

Inclusion Criteria:

- Healthy male and female volunteers between the ages of 18 and 55 years, inclusive, in good health based on medical history, physical examination, electrocardiogram (ECG), and routine laboratory tests (blood chemistry, hematology, urinalysis, and drug screen). Any routine laboratory test could be repeated per Investigator judgment;

- Body mass index (BMI) between 18 kg/m2 and 30 kg/m2, inclusive;

- Subjects must have been non-smokers or had quit smoking >6 months prior to Screening;

- Women of childbearing potential with a negative urine pregnancy test at Screening who were not breastfeeding, did not plan to become pregnant during the study, and agreed to use dual methods of birth control during the study (i.e., 2 of the following: diaphragm or cervical cap with spermicide, intrauterine device [IUD] hormonal contraceptives [stable for at least 3 months prior to Screening], male partner using condom with spermicide) from Day 1 until 60 days following the administration of study drug; or female subjects of non-childbearing potential were either surgically sterile (hysterectomy, bilateral oophorectomy, or bilateral tubal ligation) or >1 year post-menopausal with a follicle-stimulating hormone (FSH) in the post menopausal range (post-menopausal taking hormone replacement therapy [stable for at least 3 months prior to Screening] did not require an FSH level);

- All male subjects were required to use barrier contraception (condom with spermicide) in addition to having their female partner (if of childbearing potential) use another acceptable form of contraception (IUD, diaphragm with spermicide, hormonal contraceptives [stable for at least 3 months prior to Screening]) from Day 1 until 60 days following the last administration of study drug;

- Negative alcohol, cotinine, and drug screen;

- Willing to abstain from alcohol for 48 hours prior to any visit;

- Willing and able to be confined to the CPU as required by the protocol;

- Willing and able to comply with the investigational nature of the study and able to communicate well with the Principal Investigator and clinical staff; and

- Ability to comprehend and willingness to provide written informed consent in accordance with institutional and regulatory guidelines.

Exclusion Criteria:

- Subjects with evidence or history of clinically significant immunologic, hematologic, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies), surgical conditions, cancer or any other condition that, in the Investigator's opinion, might significantly interfere with the absorption, distribution, metabolism, or excretion of the study drug;

- Subjects who had received any investigational drug or device within 30 days or less than 5 half lives of investigational drug prior to dosing;

- Subjects taking any prescription or over-the-counter medications within 7 days prior to dosing, or were not willing to refrain from these medications throughout the study period;

- Subjects who had a history of alcoholism or drug abuse within 2 years prior to dosing;

- Subjects with a typical consumption of 14 alcoholic drinks weekly;

- Subjects who had a history of or positive tests for human immunodeficiency virus (HIV) or hepatitis C virus (HCV), or subjects who had a positive hepatitis B surface antigen (HBsAg) at Screening;

- Subjects who had donated blood or blood products within 30 days prior to dosing;

- Subjects with inadequate venous access;

- Subjects with an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 the upper limit of normal (ULN) at Screening or Day -1;

- Subjects with a total bilirubin >1.5 ULN at Screening or Day -1;

- Subjects who were currently undergoing treatment with weight loss medication or prior weight loss surgery (e.g., gastric bypass surgery);

- Subjects who had poor mental function or any other reason to expect subject difficulty in complying with the requirements of the study; or

- Subjects who had a history or presence of any medical condition or disease that, in the opinion of the Investigator, could interfere with the conduct of the study or would put the subject at unacceptable risk.

Género: All

Edad mínima: 18 Years

Edad máxima: 55 Years

Voluntarios Saludables: Accepts Healthy Volunteers

Oficial general
Apellido Papel Afiliación
Douglas Logan, MD Principal Investigator Medpace Clinical Pharmacology Unit
Ubicación
Instalaciones: Medpace Clinical Pharmacology Unit (CPU)
Ubicacion Paises

United States

Fecha de verificación

January 2020

Fiesta responsable

Tipo: Sponsor

Tiene acceso ampliado No
Número de brazos 2
Grupo de brazo

Etiqueta: CD24Fc

Tipo: Experimental

Descripción: Single dose of CD24Fc is administrated as intravenous infusion in one hour. There are 5 dose cohorts, 10mg, 30mg, 60mg, 120mg, 240mg. Each cohort has 6 subjects in CD24Fc and 2 subject in placebo.

Etiqueta: Saline

Tipo: Placebo Comparator

Descripción: Single dose of 100 ml normal saline is administrated as intravenous infusion in one hour.

Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Other

Enmascaramiento: Double (Participant, Investigator)

Fuente: ClinicalTrials.gov