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

• ClinicalTrials.gov Identifier: NCT04837092
• Recruitment Status: Active, not recruiting
• First Posted: April 8, 2021
• Last Update Posted: November 15, 2023
• Sponsor: Nantes University Hospital
• Collaborator: OSE Immunotherapeutics
• Information provided by (Responsible Party): Nantes University Hospital

Tracking Information

• First Submitted Date: December 3, 2020
• First Posted Date: April 8, 2021
• Last Update Posted Date: November 15, 2023
• Actual Study Start Date: June 28, 2021
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2021)

Safety of FR104 - Adverse Events with a focus on infectious complications. In particular [ Time Frame: Until Month 12 ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 6, 2021)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Kidney Transplantation

Intervention

Drug: FR104

FR104 treatment administration at day 0, day 14 then every 28 days until month 12

Study Arms

Experimental: FR104 Treatment

Intervention: Drug: FR104

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: April 6, 2021): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2025
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04837092
• Other Study ID Numbers: RC20_0007
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Nantes University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Nantes University Hospital
• Original Study Sponsor: Same as current
• Collaborators: OSE Immunotherapeutics
• Investigators: Not Provided
• PRS Account: Nantes University Hospital
• Verification Date: November 2023