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

• Register: ClinicalTrials.gov
• Last refreshed on: 8 August 2016
• Main ID: NCT02800811
• Date of registration: 20/05/2016
• Prospective Registration: No
• Primary sponsor: OSE Immunotherapeutics
• Public title: Safety, Tolerability, PK, PD, and Immunogenicity of Single and Multiple Ascending Intravenous Doses of FR104
• Scientific title: Randomized, Double-blind, Placebo-controlled, Dose-escalation Study for the Assessment of Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of Single and Multiple Intravenous Doses of FR104 in Healthy Subjects
• Date of first enrolment: April 2015
• Target sample size: 64
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02800811
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

Belgium

Contacts

• Name: Steven Ramael
• Affiliation: SGS Antwerpen

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 60 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Complication of Transplant

Rheumatoid Arthritis

Intervention(s)

Drug: Placebo

Drug: FR104

Primary Outcome(s)

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). [Time Frame: 4 months]

Secondary Outcome(s)

Terminal half-life (T1/2) of FR104 after single and two repeat iv administrations [Time Frame: 4 months]

Incidence of antidrug antibodies (ADA) and neutralizing antibodies (NAb) after single and two repeat iv administrations of FR104 [Time Frame: 4 months]

Type, incidence, severity, timing, seriousness and relatedness of abnormal cytokine levels after single and two repeat iv administrations of FR104 [Time Frame: 4 months]

Area under the concentration time curve to last quantifiable concentration [AUC (0-T)] after single and two repeat iv administrations of FR104 [Time Frame: 4 months]

Durations of 100%, 50% and 20% CD28 receptor blocade after single and two repeat iv administrations of FR104 [Time Frame: 4 months]

Secondary ID(s)

FR104-CT01

2015-000302-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors