Safety, Tolerability, PK, PD, and Immunogenicity of Single and Multiple Ascending Intravenous Doses of FR104

NCT02800811 | Completed Phase 1 DMC

• 2 other identifiers: FR104-CT012015-000302-19
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

First-in-human, phase I, randomized, double-blind, placebo-controlled, single center study evaluating single and multiple ascending intravenous doses of FR104 in healthy subjects.

Conditions

Rheumatoid Arthritis; Complication of Transplant

Keywords

FR104; CD28; immunomodulation; T regulatory cell; Pegylated monovalent anti-CD28 Fab antibody

Outcome Measures

Primary Outcomes (1)

• Type, incidence, severity, timing, seriousness and relatedness of treatment emergent adverse events, and abnormalities in laboratory parameters in healthy volunteers of FR104 compared to placebo after single (SAD) and two IV doses (MAD).

  During each treatment period, subjects will be housed and monitored at the study center from the day before dosing (Day-1) until Day 5. Thenafter, each subject will attend ambulatory visit at predefined days until day 113.

  4 months

Secondary Outcomes (5)

• Area under the concentration time curve to last quantifiable concentration [AUC (0-T)] after single and two repeat iv administrations of FR104

  4 months

• Terminal half-life (T1/2) of FR104 after single and two repeat iv administrations

  4 months

• Durations of 100%, 50% and 20% CD28 receptor blocade after single and two repeat iv administrations of FR104

  4 months

• Incidence of antidrug antibodies (ADA) and neutralizing antibodies (NAb) after single and two repeat iv administrations of FR104

  4 months

• Type, incidence, severity, timing, seriousness and relatedness of abnormal cytokine levels after single and two repeat iv administrations of FR104

  4 months

Other Outcomes (5)

• To explore through study completion the immune activity (whole blood TruCulture® assay) of FR104 (Part 1 and 2).

  4 months

• To explore through study completion the effect of FR104 on the response to keyhole limpet hemocyanin (KLH) challenge (Part 1, Cohort B).

  4 months

• To evaluate through study completion the effect of FR104 on lymphocytes subsets (Part 1: 0.2 and 0.5 mg/kg doses [Cohort A], 2 doses up to 5 (or lower than 0.5) mg/kg [Cohort B, Groups 9 and 9 bis])

  4 months

Study Arms (13)

Part 1: Cohort A, Group 1, FR104

EXPERIMENTAL

Dose: single 0.005 mg/kg.

Drug: FR104

Part 1: Cohort A, Group 2, FR104

EXPERIMENTAL

Dose: single 0.05 mg/kg.

Drug: FR104

Part 1: Cohort A, Group 3, FR104

EXPERIMENTAL

Dose: single 0.2 mg/kg.

Drug: FR104

Part 1: Cohort A, Group 4, FR104

EXPERIMENTAL

Dose: single 0.5 mg/kg.

Drug: FR104

Part 1: Cohort A, placebo

PLACEBO COMPARATOR

Placebo, single administration, double blind (1/4 healthy subject in group 1, 1/4 in group 2, 2/5 in group 3 and 2/5 in group 4).

Drug: Placebo

Part 1: Cohort B, Group 7, FR104

EXPERIMENTAL

Dose: single 0.5 mg/kg. Healthy subject naïve to KLH and that will receive a KLH challenge.

Drug: FR104

Part 1: Cohort B, Group 8, FR104

EXPERIMENTAL

Dose: single 0.2 mg/kg. Healthy subject naïve to KLH and that will receive a KLH challenge.

Drug: FR104

Part 1: Cohort B, Group 9, FR104

EXPERIMENTAL

Dose: single 1.5 mg/kg. Healthy subject naïve to KLH and that will receive a KLH challenge.

Drug: FR104

Part 1: Cohort B, Group 9 bis, FR104

EXPERIMENTAL

Dose: single 0.02 mg/kg group. Healthy subject naïve to KLH and that will receive a KLH challenge.

Drug: FR104

Part 1: Cohort B, placebo

PLACEBO COMPARATOR

placebo, single administration, double-blind: healthy subjects naïve to KLH and that will receive a KLH challenge (2/5 in each group of cohort B)

Drug: Placebo

Part 2: Group 10, FR104

EXPERIMENTAL

Dose: repeat, 0.2 mg/kg. Two administrations separated by an interval of 28 days.

Drug: FR104

Part 2: Group 11, FR104

EXPERIMENTAL

Dose: repeat, 0.5 mg/kg. Two administrations separated by an interval of 28 days.

Drug: FR104

Part 2: placebo

PLACEBO COMPARATOR

placebo, repeat, double-blind: 2/5 subjects in each group of Part 2. Two administrations separated by an interval of 28 days.

Drug: Placebo

Interventions

FR104 DRUG

GMP FR104 is provided to the site in extractable volume vials containing FR104. Appropriate Dilutions in Ringer's lactate solution is made on site.

Part 1: Cohort A, Group 1, FR104; Part 1: Cohort A, Group 2, FR104; Part 1: Cohort A, Group 3, FR104; Part 1: Cohort A, Group 4, FR104; Part 1: Cohort B, Group 7, FR104; Part 1: Cohort B, Group 8, FR104; Part 1: Cohort B, Group 9 bis, FR104; Part 1: Cohort B, Group 9, FR104; Part 2: Group 10, FR104; Part 2: Group 11, FR104

Placebo DRUG

The placebo injection contains the vehicle. For placebo dosing, vehicle is administered in accordance with the volume of study drug administered.

Part 1: Cohort A, placebo; Part 1: Cohort B, placebo; Part 2: placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects meeting all of the following criteria are eligible to participate in this study:
• Male or female, aged 18 to 60 years, extremes includes;
• Electrocardiogram (ECG) within normal range, or showing no clinically relevant deviations, as judged by the investigator; Note: a retest can be done in case of an out of range ECG value that can determine a subject's eligibility.
• Weighs at least 50 kg and no more than 100 kg and has a Body Mass Index (BMI) within normal range: 18.0≤BMI\<30.0 kg/m2;
• Negative urine test for selected drugs of abuse at screening;
• Negative alcohol breath test at screening;
• Female subject is postmenopausal or surgically sterile (having had a hysterectomy, bilateral oophorectomy, or tubal ligation);
• Female subject has a negative pregnancy test at screening;
• Non-vasectomized male subjects having a female partner of childbearing potential must agree to the use of an effective method of contraception until 90 days after the last administration of study drug ;
• Male subject has to agree not to donate sperm until 90 days after the last administration of study drug;
• Willing to adhere to the prohibitions and restrictions specified in this protocol;
• Informed Consent Form (ICF) signed voluntarily before any study-related procedure is performed, indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study;
• Subjects were to be EBV-positive as per positive IgG Epstein-Barr nuclear antigen (EBNA) test;
• Nonsmoker or light smoker, i.e., smokes maximal 5 cigarettes (or 3 cigars or 3 pipe-full) per day, and ability and willingness to refrain from smoking during confinement and ambulant visits in the clinical research center.
• For Part 1, Cohort B only:

You may not qualify if:

• Subjects meeting one or more of the following criteria are excluded from participation in this study:
• A history of any clinically significant (as determined by the investigator) cardiac, endocrinology, hematology, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, and/or other major disease or malignancy excluding non-melanoma skin cancer;
• A known allergy, hypersensitivity, or intolerance to the study drug, or to any of its compounds;
• The subject has a history of severe allergic or anaphylactic reactions;
• The subject has a history of consuming more than 21 (14 for females) units of alcoholic beverages per week or has a history of alcoholism or drug/chemical/substance abuse within past 2 years prior to screening (Note: one unit = 330 mL of beer, 110 mL of wine or 28 mL of spirits);
• Evidence or history of any clinically significant infections within the past 3 months;
• History of or evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) diagnosed by a positive QuantiFERON® TB-Gold In Tube test or a positive tuberculin skin test ("Mantoux") in case of a weak positive QuantiFERON® TB-Gold In Tube test;
• Subjects with known clinically relevant immunological disorders, or auto-immune disorders, (e.g., rheumatoid arthritis, lupus erythematosus, scleroderma, etc...);
• Subjects with a recent infection of EBV diagnosed by a positive IgM VCA;
• A positive hepatitis panel (including hepatitis B surface antigen \[HBsAg\] and anti-hepatitis C virus \[HCV\] antibodies \[Abs\]) or positive human immunodeficiency virus (HIV) antibody screens;
• The subject has a supine systolic blood pressure (SBP) \<90 or \>160 mmHg and a diastolic blood pressure (DBP) \<50 or \>90 mmHg, or pulse rate higher than 100 bpm, either at screening (blood pressure measurements taken after subject has been resting in a supine position for a minimum of 5 minutes); Note: a retest can be done in case of an out of range vital signs value that will determine a subject's eligibility. The result of the retest are considered for subject eligibility.
• The subject is pregnant or breastfeeding;
• The subject has received a vaccine within 60 days prior to study drug administration;
• The subject has received any systemic immunosuppressant agent within 6 months prior to study drug administration;
• The subject has received any antibody or biologic medicinal product within 6 months prior to study drug administration;

Sponsors & Collaborators

• OSE Immunotherapeutics: lead

Study Sites (1)

SGS Antwerpen

Antwerp, Belgium

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Steven Ramael

  SGS Antwerpen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: June 15, 2016
• Study Start: April 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: July 1, 2016
• Last Updated: July 21, 2016

Record last verified: 2016-07

Locations

BE (1)