A Prospective, Open-label, Multicenter, Randomized Study to Evaluate the Benefits and Risks of
Conversion of Existing Adolescent Renal Allograft Recipients Aged 12 to Less Than 18 Years of
Age to a Belatacept-based Immunosuppressive Regimen as Compared to Continuation of a
Calcineurin Inhibitor-based Regimen, and Their Adherence to Immunosuppressive Medications

Renal transplantation is the treatment of choice for most patients with end
stage renal disease, as it offers the best option for long-term survival with
an improved quality of life. In turn, successful kidney transplantation is
heavily dependent upon lifelong administration of immunosuppressive medications
with diverse safety profiles and off-target effects that, in and of themselves,
may have an adverse impact on quality of life, thereby predisposing to
non-adherence with the prescribed regimens.
Adolescent renal allograft recipients are at significantly higher risk of renal
allograft graft failure than are younger children or adults 31-45 years of age;

Belatacept was developed to address the medical need for a novel
immunosuppressive therapy for kidney transplant recipients that can avoid the
renal, cardiovascular, and metabolic toxicities of existing, calcineurin
inhibitor (CNI)-based regimens, while offering comparable short-term patient
and graft survival. The calcineurin inhibitors have also been associated with
adverse effects on neurological and cognitive function that may interfere with
work and school, as well as with untoward effects on physical appearance that,
in turn, may discourage regular adherence to the
prescribed oral dosing regimen.

Belatacept is administered by intravenous infusion under medical supervision
every 4 weeks, thus providing an opportunity for more frequent monitoring of
compliance with prescribed, orally administered concomitant immunosuppressive
drugs.

This study has been transitioned to CTIS with ID 2022-501677-39-00 check the CTIS register for the current data.

Evaluation of patient and functional graft survival of adolescent renal
allograft recipients converted from CNI to belatacept-based immunosuppression
at least 6 months post-transplant as compared to those of recipients remaining
on CNI at 24 months post-randomization.

This is a Phase 3b, open-label, randomized, multicenter study that will
evaluate the benefits and risks of conversion from CNI- to belatacept-based
immunosuppression following a 3-6-month CNI taper when compared to continuation
of CNI-based immunosuppression in adolescent renal
transplant recipients.

Upon meeting the enrollment criteria, participants will be randomized in a 2:1
ratio to one of two open-label treatment arms:
Arm 1: Conversion from established CNI treatment to belatacept following taper
and discontinuation of CNI.
Arm 2: Continue established CNI treatment at doses sufficient to achieve trough
whole blood concentrations (C0 levels) of 50 - 250 ng/mL (CsA) or 4 - 11 ng/mL
(TAC).

• A complete physical examination
• Vital signs
• Performing of a chest X-Ray if results are not available from one previously
done during the 6 months before this visit.
• Performing of an ECG (electrocardiogram) to check their heart rate and rhythm.
• Performing of a urine or blood pregnancy for all female participants.
• Blood draws for analyses
• Collection of a urine sample to check for protein, glucose (sugar), red and
white blood cells, and the creatinine level.
• Usage of a nasal swab to test for a current infection with SARS-CoV-2, the
coronavirus virus. This test must be negative in order for the subject to take
part in the study. If this test is positive, they may be retested one more
time, after at least 10 days.
• Completion of 3 questionnaires on the following points during the
study: Day 1 and Months 6, 12, 18, and 24; and Day 1 and Months 3, 6, 9, 12,
15, 18, 21 and 24 (child + parent).

• Group 1. subjects in this group will receive belatacept on Days 1, 15, 29,
43, and 57, and then every 28 days after that. In addition, the dose of the CNI
will be reduced, and then stopped completely, during the first 12 to 24 weeks
after the start of receiving belatacept.
• Group 2. subjects in this group will continue on the same CNI treatment they
were receiving when they entered the study.

Monitoring Safety of the subjects
The study subject will receive a dose of belatacept at all study visits, and
will be contacted by the study staff within 48 hours after each one, to see if
they have experienced any adverse effects during the 24-hour period after each
infusion.

If the study doctor suspects that the study subject may be experiencing acute
rejection, up to an additional 14 ml of blood (about 3-1/2 teaspoons) will be
collected for related testing. In addition, a kidney biopsy will be needed to
determine whether rejection is present.

Safety Follow-up Period:
When the patient stops or completes the study treatment period, they will begin
the last part of the study, known as the safety follow-up period. During this
period, the study doctor will continue to assess their health. It is important
to know, for example, if they have recovered, developed an illness, or suffered
an important adverse event.
The follow up period includes a visit for all subjects at week 8 after their
last dose of study medication. Subjects in Group 2 (CNI continuation) may have
a phone call instead of the clinic visit. If the subject is assigned to Group 1
(conversion to belatacept), and does not continue to receive belatacept after
the Month 24 (Week 104) study visit is completed, or earlier if they
prematurely discontinue belatacept before or at the time of the week 104 study
visit, they will be required to have clinic visits at 8, 12, and 24 weeks after
the last dose. Each follow-up visit should last about 1 hour.

Data Monitoring Committee: will be convened to provide oversight of
benefit-risk considerations for participants in the study and, if necessary, to
make recommendations to BMS to better ensure the ongoing safety of study
participants.