Multicenter, Randomized, Open-Label Study to Evaluate AT-1501 in Patients Undergoing Kidney Transplant

Kidney Transplant Clinical Trial

Official title:

A Phase 2, Multicenter, Randomized, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacodynamics of AT-1501 in Patients Undergoing Kidney Transplant

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04819880
• Other study ID #: AT-1501-K204
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: June 2021
• Est. completion date: March 30, 2025

Study information

• Verified date: March 2021
• Source: Eledon Pharmaceuticals
• Contact: Jennifer Areh
• Phone: 6175952605
• Email: jareh[@]eledon.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, multicenter, open-label, active control, non-inferiority study to assess the safety and efficacy of AT-1501 compared with tacrolimus in the incidence of BPAR events through 6 months post-transplant.

Description:

This is a randomized, multicenter, open-label, active control, non-inferiority study to assess the safety and efficacy of AT-1501 compared with tacrolimus. Approximately 120 de novo kidney transplant recipients will receive rabbit anti-thymoglobulin (rATG) (Thymoglobulin®) induction, corticosteroid maintenance, mycophenolate, and will be randomized 1:1.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: March 30, 2025
• Est. primary completion date: September 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

1. Male or female = 18 years of age;

2. Recipient of their first kidney transplant from a living or deceased donor;

3. If eligible for COVID-19 vaccination in their jurisdiction per local guidelines, have received a complete COVID-19 immunization schedule at least 30 days prior to Screening.

Exclusion Criteria:

1. Induction therapy, other than study-assigned rATG, planned as part of initial immunosuppressive regimen;

2. Currently treated with any systemic immunosuppressive regimen, including immunologic biologic therapies, with the exception of 5 mg prednisone or equivalent daily;

3. The patient has previously received a bone marrow transplant or any other solid organ transplant, including a kidney, or will be undergoing a multi-organ or dual-kidney transplant;

4. Will receive a kidney with an anticipated cold ischemia time of > 30 hours;

5. Will receive a kidney from a donor that meets any of the following:

• Donation after Cardiac Death (DCD) criteria; Or

• Kidney Donor Profile Index (KDPI) of >85%; Or

• Is blood group (ABO) incompatible;

6. Human leukocyte antigen identical (two haplotype match or zero HLA mismatch) donor;

7. Medical conditions that require chronic use of systemic steroids at a dose higher than 5 mg prednisone or equivalent per day;

8. History of a TE event, known hypercoagulable state, or condition requiring long term anticoagulation;

9. Current calculated panel reactive antibody (cPRA) > 20%;

10. Current or history of active tuberculosis infection. Laboratory evidence of infection (positive PPD or QuantiFERON-TB Gold) in the absence of clinical infection is exclusionary unless the patient has completed CDC recommended treatment.

a. Patients with documented BCG vaccination and a negative chest x-ray may be included at the Investigator's discretion;

11. Known hypersensitivity to tacrolimus, mycophenolate, rATG, corticosteroids, or any of their components;

12. Recipient is seronegative for EBV at Screening;

13. Positive T- or B-cell crossmatch that is due to HLA antibodies;

14. Presence of a DSA at Screening;

15. Thrombocytopenia (platelets <75,000 per mm3), leukopenia (WBC <3,000 per mm3), or anemia (hemoglobin <8 g/ dL) at Screening;

16. Desensitization therapy within 6 months of transplant;

Related Conditions & MeSH terms

• Kidney Transplant

Intervention

Drug:
• AT-1501
Patients randomized to treatment arm A will receive induction therapy then AT-1501 and mycophenolate.
• Tacrolimus + mycophenolate
Patients randomized to treatment arm B will receive induction therapy then Tacrolimus and mycophenolate.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eledon Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in eGFR		Month 1 to 3, 6, 12, 18, 24, and 36 months post-transplant
Other	iBox score	iBox is a validated tool for predicting the risk of kidney transplant loss based on artificial intelligence. Range of score is 0%-100%, higher score indicates better kidney survival.	12, 24 and 36 months post transplant
Other	Incidence of donor specific antibodies (DSA)		1, 3, 6, 9, 12, 18, 24, and 36 months post-transplant and at the time of for-cause biopsies
Other	Incidence of donor derived cell-free DNA		3, 6, 9 and 12 months post-transplant and at the time of for-cause biopsies
Other	Rate of composite endpoint	(graft failure, BPAR, or death)	24 and 36 months post-transplant
Other	Incidence of anti-AT-1501 antibodies		3, 6, 12, 24, and 36 months of treatment
Other	Pharmacokinetic profile- area under the curve		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- maximum concentration		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- maximum concentration at steady state		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- volume of distribution , and volume of distribution at steady state		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- half-life		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile-minimum concentration		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile-minimum concentration at steady state		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile-clearance		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- elimination constant		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- time to maximum concentration at steady state		Day 1 and Month 3 in 10 patients
Other	Pharmacokinetic profile- time to maximum concentration		Day 1 and Month 3 in 10 patients
Primary	Incidence of BPAR	T cell-mediated rejection Banff Grade = 1A and antibody-mediated rejection events	6 months post-transplant
Primary	Safety - SAEs , TEAEs and AEoSI	Incidence of serious adverse events (SAEs), treatment emergent adverse events (TEAEs), and AEs of special interest (AEoSI)	Through study completion, an average 2 years
Secondary	Patient and graft survival		12 months post transplant
Secondary	Proportion of patients displaying =10% decrease in estimated glomerular filtration rate (eGFR)		Between 1 and 12 months post transplant
Secondary	Rate of composite endpoint	graft failure, BPAR, or death	12 months post transplant