Safety, Pharmacokinetics, and Efficacy of AT 1501 in Patients Undergoing Kidney Transplant

Sponsor

Eledon Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05027906

Collaborator

(none)

Enrollment

Location

Arm

19.4

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety, PK, and efficacy of AT 1501 in patients undergoing kidney transplantation.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant	Drug: AT-1501	Phase 1/Phase 2

Detailed Description

This study will evaluate the safety, PK, and efficacy of AT 1501 in patients undergoing kidney transplantation. Up to 12 de novo kidney transplant recipients will receive AT-1501 in combination with rATG induction with corticosteroids (CS), and mycophenolate as maintenance therapy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Phase 1b, open label, single-arm studyPhase 1b, open label, single-arm study

Masking:

None (Open Label)

Masking Description:

None ( Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b, Multicenter, Open Label Study to Evaluate the Safety, Pharmacokinetics and Efficacy of AT 1501 in Patients Undergoing Kidney Transplant

Actual Study Start Date :

Feb 18, 2022

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Oct 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AT-1501 Single Arm AT-1501 monoclonal antibody targeting CD40L given as an IV infusion	Drug: AT-1501 Investigative Arm

Arm

Intervention/Treatment

Experimental: AT-1501 Single Arm

AT-1501 monoclonal antibody targeting CD40L given as an IV infusion

Drug: AT-1501

Investigative Arm

Outcome Measures

Primary Outcome Measures

Safety Incidences [Through study completion, an average up to 20 months]
Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and Adverse Events of Special Interest (AEoSI)
Pharmacokinetic- PK profile [Day 1 and at steady state Month 3]
PK profile of the first dose of AT 1501 and at steady state Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (Ct), calculated using the linear trapezoidal method (AUC0-t)
Pharmacokinetic- Area under the plasma concentration [Day 1 and at steady state Month 3]
Area under the plasma concentration versus time curve from time 0 extrapolated to infinity, calculated using the linear trapezoidal method (AUC0-inf)
Pharmacokinetic- Cmax [Day 1 and at steady state Month 3]
Maximum observed plasma concentration (Cmax)
Pharmacokinetic- Tmax [Day 1 and at steady state Month 3]
Time to reach maximum observed plasma concentration (Tmax)
Pharmacokinetic- Ke [Day 1 and at steady state Month 3]
Terminal elimination rate constant (Ke)
Pharmacokinetic- (t1/2) [Day 1 and at steady state Month 3]
Terminal phase half-life (t1/2)
Pharmacokinetic- CL [Day 1 and at steady state Month 3]
Clearance (CL)
Pharmacokinetic- (Vdss) [Day 1 and at steady state Month 3]
Volume of distribution at steady state (Vdss)

Other Outcome Measures

Incidence of BPAR [6 and 12 months post-transplant]
Incidence of BPAR (T cell-mediated rejection [TCMR] Banff Grade ≥ 1A and antibody mediated rejection [AMR])
Change in eGFR [Month 1 to Month 3, 6, 12, and 15 post-transplant]
Changes in eGFR
Rate of composite endpoint [12 months post-transplant]
Rate of composite endpoint (graft failure, BPAR, or death)
Incidence of DSA [1, 3, 6, 9, 12, and 15 months post-transplant and at the time of for cause biopsies]
DSA
Incidence of donor derived cell free DNA (dd-cfDNA) [3, 6, 9, 12, and 15 months post-transplant and at the time of for cause biopsies]
(dd-cfDNA)
Pharmacodynamic Studies [Day 0 and Months 3, 6, 9, 12, and 15 post-transplant and at the time of for-cause biopsies]
CD40L receptor occupancy and gene expression studies
Trough levels of AT-1501 [Days 7, 14, 21 and Months 1, 3, 6, 9, 12, and 15 post-transplant]
Trough levels
Anti-AT-1501 antibody studies [Months 1, 3, 6, 12, and 15 post-transplant]
Incidence of anti- AT-1501 antibodies

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female ≥ 18 years of age
Recipient of their first kidney transplant from a living or deceased donor

Exclusion Criteria:

Induction therapy, other than study assigned rATG, planned as part of initial immunosuppressive regimen
Currently treated with any systemic immunosuppressive regimen, including immunologic biologic therapies, with the exception of 5 mg prednisone or equivalent daily;
Previous treatment with AT 1501 or any other anti CD40LG therapy
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
Will receive a kidney with an anticipated cold ischemia time of > 30 hours;
Will receive a kidney from a donor that meets any of the following:

• Donation after Cardiac Death (DCD) criteria; or

Extended Criteria Donor (ECD) criteria, defined as:

Is blood group (ABO) incompatible; or
Age ≥ 60 years; or
Age 50-59 years with any 2 of the following criteria
Death due to cerebrovascular accident
History of hypertension
Terminal creatinine ≥ 133 μmol/L

Human leukocyte antigen identical (two haplotype match or zero HLA mismatch) donor
Medical conditions that require chronic use of systemic steroids at a dose higher than 5 mg prednisone or equivalent per day
History of a TE event, known hypercoagulable state, or condition requiring long term anticoagulation:
Patients with a history of clotted venous access not requiring long term anticoagulation may be included at the Investigator's discretion if have no other history of TE events or known hypercoagulable state