Phase I/II Study of FR104 First Administration in Patient with Renal Transplantation: FIRsT Study

Phase 1

Active, not recruiting

• Conditions: Kidney Transplantation
• Interventions: Drug: FR104

• Registration Number: NCT04837092
• Lead Sponsor: Nantes University Hospital

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 available

Study Timeline

• Study First Submitted: 2020-12-03
• Study First Submitted QC: 2021-04-06
• Study First Posted: 2021-04-08
• Study Start: 2021-06-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-29
• Primary Completion: 2025-03
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 10

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FR104 Treatment	FR104	-

Primary Outcome Measures

Name	Time	Method
Safety of FR104 - Adverse Events with a focus on infectious complications. In particular	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.

Secondary Outcome Measures

Name	Time	Method
Efficacy on Renal function	Month 6 and Month 12	Calculated glomerular filtration rate (CKD EPI) at each visit.
Efficacy on clinically-treated acute rejections	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 multiples rejection episodes	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 steroid-resistant episodes	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 graft survival	Month 12	Renal dialysis or new kidney transplant up to Month 12
Treatment failure time	Month 12	Time to treatment failure up to M12 (Biopsy-proven acute rejection, Graft Loss or Death)
Evaluate the appearance of Donor specific Antibodies	Month 12	Appearance of Donor specific Antibodies
Efficacy on Biopsy-proven acute rejection (BPAR)	Month 12	Acute cellular rejection seen on renal biopsy for cause up to Month 12 (per Banff criteria 2017)
Efficacy on chronic allograft nephropathy	Month 12	Chronic allograft nephropathy seen on renal biopsy for cause up to Month 12
Evaluate the first Biopsy-proven acute rejection time	Month 12	Time to the first Biopsy-proven acute rejection

Trial Locations

Locations (1)

Blancho; 🇫🇷 Nantes, France