Kidney TransplantationPhase 1/2NCT02217410

CCFZ533X2201 - PoC Study in de Novo Renal Transplantation

A Phase 1/2 study testing CFZ533, Tacrolimus (Tac) and Mycophenolate mofetil (MMF) in people with Kidney Transplantation, run by Novartis Pharmaceuticals at 14 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study was to investigate the safety, tolerability, pharmacokinetics (PK) and potential for CFZ533 to replace calcineurin inhibitors (CNI), while providing a similar rate of acute rejection prophylaxis and renal function in a de novo renal transplant population receiving an allograft from standard… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Kidney Transplantation
What is being tested?: CFZ533, Tacrolimus (Tac) and Mycophenolate mofetil (MMF)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 59 participants
Where: 14 sitesin 4 countries
Study dates: 5 Feb 2015to 29 Nov 2017
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Main Inclusion Criteria:

Written informed consent must be obtained before any assessment is performed.
Recipients of a kidney transplant from a heart-beating deceased, living unrelated or non-human leukocyte antigen (HLA) identical living related donor.
Recipients of a kidney with a cold ischemia time (CIT) < 30 hours.

Main Exclusion Criteria:

Recipients of an organ from a non-heart beating donor.
ABO incompatible or complement-dependent lymphocytotoxic (CDC) crossmatch positive transplant.
Subjects receiving a second kidney allograft, unless the first allograft was lost due to surgical complication.
Subjects at high immunological risk for rejection
Subjects at risk for tuberculosis (TB)
Subject with severe systemic infections, current or within the two weeks prior to randomization/enrollment.
Any additional contraindication to the use of tacrolimus or mycophenolate mofetil according to the national labeling information of these products (see local product label).

Trial locations and contacts

14 sites in 4 countries.

Country

City, postcode or hospital

14 sites in 4 countries

United States6 sites

Novartis Investigative Site
Ann Arbor, Michigan, 48109 5271
Novartis Investigative Site
Aurora, Colorado, 80045
Novartis Investigative Site
Baltimore, Maryland, 21201
Novartis Investigative Site
Cincinnati, Ohio, 45267-0585
Novartis Investigative Site
Detroit, Michigan, 48202
Novartis Investigative Site
Livingston, New Jersey, 07039

Other trials in United States

Germany4 sites

Novartis Investigative Site
Berlin, D-13353
Novartis Investigative Site
Essen, 45147
Novartis Investigative Site
Hamburg, 20246
Novartis Investigative Site
Heidelberg, 69120

Other trials in Germany

Netherlands3 sites

Novartis Investigative Site
Groningen, 9713 GZ
Novartis Investigative Site
Rotterdam, 3000 CA
Novartis Investigative Site
Utrecht, The Netherlands, 3508 GA

Other trials in Netherlands

Brazil1 site

Novartis Investigative Site
São Paulo, São Paulo, 04038-002

Other trials in Brazil

About this study

Official title: A 12-month Randomized, Multiple Dose, Open-label, Study Evaluating Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) and Efficacy of an Anti-CD40 Monoclonal Antibody, CFZ533, in Combination With Mycophenolate Mofetil (MMF) and Corticosteroids (CS), With and Without Tacrolimus (Tac), in de Novo Renal Transplant Recipients

Conditions: Kidney Transplantation
Being tested: CFZ533, Tacrolimus (Tac), Mycophenolate mofetil (MMF), Corticosteroids (CS), anti-IL2 Induction
Keywords: renal, de novo,

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CFZ533Biological
Tacrolimus (Tac)Drug
Mycophenolate mofetil (MMF)Drug
Corticosteroids (CS)Drug
anti-IL2 InductionBiological

Study groups in NCT02217410
Study group	Role	What they receive
Regimen A	Experimental	CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS). Receives: Biological: CFZ533; Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS)
Regimen B	Experimental	CFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction Receives: Biological: CFZ533; Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction
Regimen C	Active comparator	Standard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction] Receives: Drug: Tacrolimus (Tac); Drug: Mycophenolate mofetil (MMF); Drug: Corticosteroids (CS); Biological: anti-IL2 Induction

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Cmax Pharmacokinetic Parameter- Part I
Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I
Measured: Day 1
Mean Tmax Pharmacokinetic Parameter - Part I
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Measured: Day 1
Mean AUClast Pharmacokinetic Parameter - Part I
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Measured: Day 1
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II
To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale.
An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.
Measured: 3, 6, 9, and 12 months

Secondary outcomes (7)

Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1
To quantify the change from baseline and recovery of peripheral blood total soluble CD40 and total soluble CD154
Measured: Baseline to end of study (Day 1, Day 29, Day 337)
Free CD40 and Total CD40 on B Cells - Part II
The magnitude and duration of peripheral blood CD40 occupancy. MESF: molecules of equivalent soluble fluorochrome
Measured: Baseline to end of study (Day 1/predose)
Anti-CFZ533 Antibodies - Part I
To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
Measured: Baseline to end of study
Anti-CFZ533 Antibodies - Part II
To evaluate the immunogenicity of CFZ533 via the quantitative analysis of anti-CFZ533 antibodies
Measured: Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)
eGFR - Part II
Renal function as assessed by MDRD (Modification of Diet in Renal Disease) formula.
eGFR: Estimated glomerular filtration rate
Measured: Day 1, Day 29, Day 337,
CFZ533 Plasma PK Concentrations - Part II
Quantify the systemic concentrations of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods. A full pharmacokinetic analysis can be performed on the concentration-time data to evaluate the impact of renal transplantation on the various medications used in the treatment regimen.
Measured: throughout study period (day 84 to day 336)
Total sCD40 Plasma Concentrations - Part II
To quantify the change from baseline and recovery of peripheral blood total soluble CD40
Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Feb 201529 Nov 2017

First posted15 Aug 2014 (estimated)
Study start5 Feb 2015
Primary completion29 Nov 2017
Study completion29 Nov 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Kidney TransplantationStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 59 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02217410
Sponsor's protocol ID: CCFZ533X2201
Status last verified: Sep 2021
First submitted: 7 Aug 2014
Last updated: 28 Sep 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Kidney Transplantation trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 12-month Randomized, Multiple Dose, Open-label, Study Evaluating Safety, Tolerability, Pharmacokinetics/Pharmacodynamics (PK/PD) and Efficacy of an Anti-CD40 Monoclonal Antibody, CFZ533, in Combination With Mycophenolate Mofetil (MMF) and Corticosteroids (CS), With and Without Tacrolimus (Tac), in de Novo Renal Transplant Recipients
ClinicalTrials.gov ID: NCT02217410
Acronym / sponsor ID: CCFZ533X2201
Conditions: Kidney Transplantation
Keywords: renal, de novo,
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 59 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 5 Feb 2015 (actual)
Primary completion: 29 Nov 2017 (actual)
Study completion: 29 Nov 2017 (actual)
First posted: 15 Aug 2014 (estimated)
Results: Posted 21 Dec 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Regimen A	Experimental	Biological: CFZ533, Drug: Tacrolimus (Tac), Drug: Mycophenolate mofetil (MMF), Drug: Corticosteroids (CS)CFZ533 administered with the contemporary standard of care (SoC) consists of concentration-controlled tacrolimus (Tac), combined with mycophenolate mofetil (MMF) and corticosteroids (CS).
Regimen B	Experimental	Biological: CFZ533, Drug: Mycophenolate mofetil (MMF), Drug: Corticosteroids (CS), Biological: anti-IL2 InductionCFZ533 administered with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction
Regimen C	Active comparator	Drug: Tacrolimus (Tac), Drug: Mycophenolate mofetil (MMF), Drug: Corticosteroids (CS), Biological: anti-IL2 InductionStandard of care (SoC) [concentration-controlled tacrolimus (Tac) combined with mycophenolate mofetil (MMF) and corticosteroids (CS) with anti-IL2 induction]

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CFZ533	Biological	Regimen A, Regimen B
Tacrolimus (Tac)	Drug	Regimen A, Regimen C
Mycophenolate mofetil (MMF)	Drug	Regimen A, Regimen B, Regimen C
Corticosteroids (CS)	Drug	Regimen A, Regimen B, Regimen C
anti-IL2 Induction	Biological	Regimen B, Regimen C

Primary outcome

Mean Cmax Pharmacokinetic Parameter- Part I
Time frame: Day 1
Pharmacokinetics as defined by the systemic concentrations and Cmax of certain immunosuppressant medications used in Part I
Mean Tmax Pharmacokinetic Parameter - Part I
Time frame: Day 1
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Mean AUClast Pharmacokinetic Parameter - Part I
Time frame: Day 1
Quantify pharmacokinetics of CFZ533 in combination with MMF, CS, and tacrolimus in de novo renal transplant patients during the treatment and follow-up periods.
Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II
Time frame: 3, 6, 9, and 12 months
To assess the activity of the investigational arm as compared to the standard of care control arm in de novo renal transplant patients as measured by the frequency and severity of tBPAR as measured on the Banff classification scale. An adjudication was performed on all on cause renal biopsies by an independent expert committee blinded to therapy.

7 secondary outcomes

Total Soluble CD40 and Total Soluble CD154 Concentrations in Plasma - Part 1
Time frame: Baseline to end of study (Day 1, Day 29, Day 337)
Free CD40 and Total CD40 on B Cells - Part II
Time frame: Baseline to end of study (Day 1/predose)
Anti-CFZ533 Antibodies - Part I
Time frame: Baseline to end of study
Anti-CFZ533 Antibodies - Part II
Time frame: Baseline to end of study (screening, baseline, Day 141, Day 225, Day 309, Study Completion)
eGFR - Part II
Time frame: Day 1, Day 29, Day 337,
CFZ533 Plasma PK Concentrations - Part II
Time frame: throughout study period (day 84 to day 336)
Total sCD40 Plasma Concentrations - Part II
Time frame: 12 months

Results and safety

Results posted to the registry on 21 Dec 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CFZ533 + TAC + MMF (Part 1)	7	6
CFZ533 + MMF (Part 2)	34	30
Tac + MMF (Part 2)	18	13

Primary outcome: Mean Cmax Pharmacokinetic Parameter- Part I

Time frame: Day 1. Mean (Standard Deviation). Unit: ug/mL

Measure	CFZ533 + TAC + MMF (Part 1) n = 7
Value	66.3 (12.3)

Population analysed: The PK Analysis Set included all patients with at least one available valid (i.e., not flagged for exclusion) PK concentration measurement, who received study drug and experienced no protocol deviations with relevant impact on PK data.

Primary outcome: Mean Tmax Pharmacokinetic Parameter - Part I

Time frame: Day 1. Median (Full Range). Unit: day

Measure	CFZ533 + TAC + MMF (Part 1) n = 7
Value	0.237 (0 to 1.02)

Primary outcome: Mean AUClast Pharmacokinetic Parameter - Part I

Time frame: Day 1. Mean (Standard Deviation). Unit: day*ug/mL

Measure	CFZ533 + TAC + MMF (Part 1) n = 7
Value	367 (52.0)

Primary outcome: Efficacy as Defined by the Frequency and Severity (Banff Classification) of Treated Biopsy Proven Acute Rejection (tBPAR) Adjudicated Data - Part II

Time frame: 3, 6, 9, and 12 months. Number. Unit: events

Measure	CFZ533 + MMF (Part 2) n = 33	Tac + MMF (Part 2) n = 18
Month 3	6	2
Month 6	7	3
Month 9	7	3
Month 12	7	3

CFZ533 + MMF (Part 2) vs Tac + MMF (Part 2): Mean Difference (Final Values): 0.095 (95% CI -0.067 to 0.263), p = 0.8976, Bayesian posterior probability
CFZ533 + MMF (Part 2) vs Tac + MMF (Part 2): Mean Difference (Final Values): 0.093 (95% CI -0.084 to 0.271), p = 0.8836, Bayesian posterior probability
CFZ533 + MMF (Part 2) vs Tac + MMF (Part 2): Mean Difference (Final Values): 0.093 (95% CI -0.085 to 0.272), p = 0.8822, Bayesian posterior probability

Population analysed: PD analysis set included all Patients in the Full Analysis set with available PD data and no protocol deviations with relevant impact on PD data.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 3 years.. Other adverse events reported at 2% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CFZ533 + TAC + MMF (Part 1)	4 of 7 (57.1%)	7 of 7 (100%)	0 of 7
CFZ533 + MMF (Part 2)	21 of 34 (61.8%)	33 of 34 (97.1%)	0 of 34
Tac + MMF (Part 2)	12 of 18 (66.7%)	18 of 18 (100%)	0 of 18
Total	37 of 59 (62.7%)	58 of 59 (98.3%)	0 of 59

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Plain Language Trial Summary is available on novartisclinicaltrials.comLink provided by the sponsor.
Individual participant dataSharing planned: Undecided. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

14 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing CFZ533, Tacrolimus (Tac) and Mycophenolate mofetil (MMF) in people with Kidney Transplantation, run by Novartis Pharmaceuticals at 14 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Germany, Netherlands, Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Dec 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Cmax Pharmacokinetic Parameter- Part I (time frame: Day 1). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02217410.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2021.