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

NCT ID: NCT02800811

Last Updated: 2016-07-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2016-07-31

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.

Detailed Description

This study is a 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.

64 healthy male and female subjects are selected according to the inclusion and exclusion criteria, i.e., 50 subjects in Part 1 (SAD: 2 cohorts of 22 [Cohort A], 28 [Cohort B], respectively) and 14 subjects in Part 2 (MAD). The total duration of the study is 10 months.

All FR104 doses are administered intravenously by a slow infusion of at least 30 minutes. A staggered approach is observed within all dose levels. An interval of at least 14 days (last to first administration) is observed between all dose levels. Individual subjects on a same day of dosing are dosed at least 60 minutes apart.

Conditions

Rheumatoid Arthritis; Complication of Transplant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Part 1: Cohort A, Group 1, FR104

Dose: single 0.005 mg/kg.

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 2, FR104

Dose: single 0.05 mg/kg.

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 3, FR104

Dose: single 0.2 mg/kg.

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 4, FR104

Dose: single 0.5 mg/kg.

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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, placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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 B, Group 7, FR104

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

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 B, Group 8, FR104

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

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 B, Group 9, FR104

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

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 B, Group 9 bis, FR104

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

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 B, placebo

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Part 2: Group 10, FR104

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

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 2: Group 11, FR104

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

Group Type: EXPERIMENTAL

FR104

Intervention Type: 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 2: placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

FR104

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects meeting all of the following criteria are eligible to participate in this study:

1. Male or female, aged 18 to 60 years, extremes includes;

2. In good health condition [medically stable] as determined on the basis of medical history, vital signs, clinical laboratory testing, and general physical examination performed at screening; Note: a retest can be done in case of an out of range clinical laboratory test value that will determine a subject's eligibility. This retest is preferably to be done at an unscheduled visit. The result of the retest are considered for subject eligibility. If the retest is outside normal reference ranges, the subject are eligible for inclusion only if the investigator judges the abnormalities to be not clinically significant.

3. 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.

4. 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;

5. Negative urine test for selected drugs of abuse at screening;

6. Negative alcohol breath test at screening;

7. Female subject is postmenopausal or surgically sterile (having had a hysterectomy, bilateral oophorectomy, or tubal ligation);

8. Female subject has a negative pregnancy test at screening;

9. 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 ;

10. Male subject has to agree not to donate sperm until 90 days after the last administration of study drug;

11. Willing to adhere to the prohibitions and restrictions specified in this protocol;

12. 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;

13. Subjects were to be EBV-positive as per positive IgG Epstein-Barr nuclear antigen (EBNA) test;

14. 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:

15. The subject did not undergo a KLH challenge.

Exclusion Criteria

Subjects meeting one or more of the following criteria are excluded from participation in this study:

1. 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;

2. A known allergy, hypersensitivity, or intolerance to the study drug, or to any of its compounds;

3. The subject has a history of severe allergic or anaphylactic reactions;

4. 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);

5. Evidence or history of any clinically significant infections within the past 3 months;

6. 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;

7. Subjects with known clinically relevant immunological disorders, or auto-immune disorders, (e.g., rheumatoid arthritis, lupus erythematosus, scleroderma, etc...);

8. Subjects with a recent infection of EBV diagnosed by a positive IgM VCA;

9. 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;

10. 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.

11. The subject is pregnant or breastfeeding;

12. The subject has received a vaccine within 60 days prior to study drug administration;

13. The subject has received any systemic immunosuppressant agent within 6 months prior to study drug administration;

14. The subject has received any antibody or biologic medicinal product within 6 months prior to study drug administration;

15. The subject has received any systemic steroid within 2 months prior to study drug administration;

16. Use of a prohibited therapy within 14 days prior to study drug administration;

17. Receipt of any investigational drug within 30 days or ten half-lives, whichever is longer, prior to the initial study drug administration;

18. The subject is participating in another clinical trial or has participated in another dose group of the current trial;

19. Had a significant blood loss (including blood donation [>500 mL]) or having had a transfusion of any blood product within the 60 days or donated plasma within 7 days prior to the initial study drug administration;

20. A condition that, in the opinion of the investigator, could compromise the well-being of the subject or course of the study, or prevent the subject from meeting or performing any study requirements.

21. Intent to visit regions where tuberculosis and mycosis are endemic during the period of 3 months after dosing (4 months after dosing for subjects in Cohort C) , i.e., deserts areas, Eastern Europe, Central and South America, Africa except Egypt, Russia, Asia, Indonesia.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

OSE Immunotherapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Ramael

Role: PRINCIPAL_INVESTIGATOR

SGS Antwerpen

Locations

SGS Antwerpen

Antwerp, , Belgium

Countries

Belgium

Other Identifiers

2015-000302-19

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

FR104-CT01

Identifier Type: -

Identifier Source: org_study_id