Phase I/II Study of FR104 First Administration In Patient With Renal Transplantation: FIRsT Study

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Kidney Transplantation

Intervention / Treatment
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* Drug: FR104


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years old Signed and dated written informed consent prior to any study procedure First kidney transplantation Willing and able to participate to the study 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 Women of childbearing potential must have a negative urinary pregnancy test the day of transplantation 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 Recipient of a kidney from deceased donor - Recipient of a de novo kidney transplant able to start the immunosuppressive regimen at the protocol-specified time point Recipients of a kidney with a cold ischemia time < 36 hours Patients with French social security Exclusion Criteria: Recipient of a kidney from living donor 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) Any retransplantation and combined transplantations ABO incompatible transplantation HIV-positive, EBV-negative or suffering active viral hepatitis B (AgHbs positive excluded) or hepatitis C, syphilis serology- positive recipient CMV negative recipients of CMV positive donors (R-D+) Patient with known history of tuberculosis 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 A known allergy, hypersensitivity, or intolerance to the study drug, or to any of its components Previous history of cancer (except appropriately treated non-melanoma skin cancer or localized cervical cancer, or other local tumors considered cured) Pregnant woman or likely to become pregnant or nursing Patient under guardianship or trusteeship Patient participating in another interventional clinical trial Live viral or bacterial vaccines/treatment agents given from 3 months prior to FR104 administration (12 months for BCG vaccine)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FR104 Treatment<br> | Drug: FR104<br>* FR104 treatment administration at day 0, day 14 then every 28 days until month 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of FR104 - Adverse Events with a focus on infectious complications. In particular | Type, severity (grades 3 and 4 adverse effects)., number and percent of Adverse Events with a focus on infectious complications. In particular, the following cumulative incidences will be calculated: Incidence of bacterial, fungal, viral, or parasitic infection, incidence of new malignancies, lymphopenia, anemia, leucopenia, cytopenia or biochemical disturbances related to the study drug. | Until Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy on Renal function | Calculated glomerular filtration rate (CKD EPI) at each visit. | Month 6 and Month 12 | 
| Efficacy on Biopsy-proven acute rejection (BPAR) | Acute cellular rejection seen on renal biopsy for cause up to Month 12 (per Banff criteria 2017) | Month 12 | 
| Efficacy on clinically-treated acute rejections | Graft acute rejection up to Month 12. Number of AE related to treatment. Incidence and grade of rejection proven on Biopsy analysed after M12. | Month 12 | 
| Efficacy on steroid-resistant episodes | Steroid resistant episodes up to Month 12. Corticoresistant rejection up to month 12 defined as non response at day 5-6 after steroid boluses. | Month 12 | 
| Efficacy on multiples rejection episodes | Rejection episodes up to Month 12. Number of rejection after M12. According to histology. Incidence of biopsy-proven rejection (by banff grade). | Month 12 | 
| Efficacy on chronic allograft nephropathy | Chronic allograft nephropathy seen on renal biopsy for cause up to Month 12 | Month 12 | 
| Efficacy on graft survival | Renal dialysis or new kidney transplant up to Month 12 | Month 12 | 
| Treatment failure time | Time to treatment failure up to M12 (Biopsy-proven acute rejection, Graft Loss or Death) | Month 12 | 
| Evaluate the first Biopsy-proven acute rejection time | Time to the first Biopsy-proven acute rejection | Month 12 | 
| Evaluate the appearance of Donor specific Antibodies | Appearance of Donor specific Antibodies | Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FR104, Renal transplant