Clinical trial NCT04837092: Phase I/II Study of FR104 First Administration in Patient with Renal Transplantation: FIRsT Study
Official title: A Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of FR104, a Novel Antagonist Pegylated Anti-CD28 Fab' Antibody Fragment in De Novo Renal Transplant Patients
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Kidney Transplantation
Keywords: FR104
Renal transplant
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: OSE Immunotherapeutics
First posted: 2021-04-08
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety, tolerability, pharmacokinetics (PK) of FR104 as well as its potential clinical effect on acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard criteria donors.


Eligibility criteria: Inclusion Criteria:

1. Male or female ≥ 18 years old
2. Signed and dated written informed consent prior to any study procedure
3. First kidney transplantation
4. Willing and able to participate to the study
5. Women of childbearing potential must use appropriate method(s) of contraception during the clinical trial (oral contraception, implant or intrauterine device) throughout the study period and for 90 days after the last dose of FR104
6. Women of childbearing potential must have a negative urinary pregnancy test the day of transplantation
7. All sexually active male subjects must agree to use an adequate method of contraception throughout the study period and for 90 days after the last dose of study drug and agree to no sperm donation until the end of the study, or for 90 days after the last dose of FR104, whichever is longer
8. Recipient of a kidney from deceased donor -
9. Recipient of a de novo kidney transplant able to start the immunosuppressive regimen at the protocol-specified time point
10. Recipients of a kidney with a cold ischemia time \< 36 hours
11. Patients with French social security

Exclusion Criteria:

1. Recipient of a kidney from living donor
2. Patient at high immunological risk of rejection as determined for assessment of anti-donor reactivity:

   High TGI \>20% or Presence of pre-formed DSA with MFI\>500 (results 12 weeks prior to enrollment are acceptable if no blood transfusion or abortion occurred during this period)
3. Any retransplantation and combined transplantations
4. ABO incompatible transplantation
5. HIV-positive, EBV-negative or suffering active viral hepatitis B (AgHbs positive excluded) or hepatitis C, syphilis serology- positive recipient
6. CMV negative recipients of CMV positive donors (R-D+)
7. Patient with known history of tuberculosis
8. Uncontrolled concomitant infection or any other unstable medical condition (heart failure, severe liver disease, psychiatric disorders, substance abuse) that could interfere with the study objectives
9. A known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components
10. Previous history of cancer (except appropriately treated non-melanoma skin cancer or localized cervical cancer, or other local tumors considered cured)
11. Pregnant woman or likely to become pregnant or nursing
12. Patient under guardianship or trusteeship
13. Patient participating in another interventional clinical trial
14. Live viral or bacterial vaccines/treatment agents given from 3 months prior to FR104 administration (12 months for BCG vaccine)

Primary outcomes:
measure: Safety of FR104 - Adverse Events with a focus on infectious complications. In particular
timeFrame: Until Month 12
Secondary outcomes:
measure: Efficacy on Renal function
timeFrame: Month 6 and Month 12
measure: Efficacy on Biopsy-proven acute rejection (BPAR)
timeFrame: Month 12
measure: Efficacy on clinically-treated acute rejections
timeFrame: Month 12
measure: Efficacy on steroid-resistant episodes
timeFrame: Month 12
measure: Efficacy on multiples rejection episodes
timeFrame: Month 12
measure: Efficacy on chronic allograft nephropathy
timeFrame: Month 12
measure: Efficacy on graft survival
timeFrame: Month 12
measure: Treatment failure time
timeFrame: Month 12
measure: Evaluate the first Biopsy-proven acute rejection time
timeFrame: Month 12
measure: Evaluate the appearance of Donor specific Antibodies
timeFrame: Month 12
Other outcomes:
Locations:
city: Nantes
country: France
facility: Blancho
Study officials:
References: