Pediatric Kidney DiseasePhase 3Pro-TacNCT06057545

Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation

A Phase 3 study testing Envarsus® and Prograf in people with Pediatric Kidney Disease, run by University Hospital, Essen at 4 sites in Germany.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

Who is it for?: Ages 8 to 18 years
Conditions the study is for: Pediatric Kidney Disease
What is being tested?: Envarsus® and Prograf
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 30 participants
Where: 4 sitesGermany
Study dates: 25 Apr 2023to Mar 2025
Phase: Phase 3
Are there results?: None posted in the registry

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 8 to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

caucasian paediatric kidney transplant recipients (single-organ recipients)
aged ≥ 8 years but ≤ 18 years who are under tacrolimus (Prograf®) therapy and who are able to swallow tablets with a minimum dose of 0.75 mg / day Envarsus®
not less than 6 months after transplantation
stable kidney function (delta eGFR < 10 ml/min/1.73 m2 (CKID formula) over the last 3 months)
women of childbearing potential and women without childbearing potential
patient/parents/legal guardian(s) must be capable of understanding purpose and risks of the study
signed informed consent obtained by patient and parents/legal guardians

Who cannot join

coefficient of variation of tacrolimus trough levels > 0.35 over the previous 6 months
pregnancy/breast feeding
instable kidney function
hypersensitivity to any of the components of the medications used
not eligible for any reason according to the investigator's valuation
known positive HIV-1 or HCV test
participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior to enrolment)

Trial locations and contacts

4 sites in 1 country.

Julia Grimm contact

+4920172377414

julia.grimm@uk-essen.de

Germany4 sites, 4 recruiting

University Hospital Cologne, Pediatrics
Cologne
Lutz Weber, Prof. Dr.
Recruiting
University Hospital of Essen, Pediatrics II
Essen
Lars Pape, Prof. Dr.
Recruiting
University Hospital of Hamburg-Eppendorf
Hamburg
Jun Oh, Prof. Dr.
Recruiting
University Hospital of Heidelberg
Heidelberg
Burkhard Tönshoff, Prof. Dr.
Recruiting

Other trials in Germany

About this study

Official title: A Multi-center Interventional Study to Assess Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation

Recently, a new prolonged-release tablet version of tacrolimus (Envarsus®) using the so-called MeltDose™ (US Patent No. 7,217,431) drug-delivery technology has been approved as immunosuppressive medication for patients after kidney and liver transplantation in adults but not yet in children. Studies in adults proved that Envarsus® provides the same therapeutic effectiveness as the conventional immediate-release tacrolimus formulation (Prograf®) with improved bioavailability, a more consistent pharmacokinetic profile and reduced peak to trough which might result in reduced tacrolimus dosing and subsequently reduced CNI related toxicity. Furthermore, the once daily formulation might result in improved drug adherence.

The aim of this study is to assess pharmacokinetic profiles of Envarsus® as well as effectiveness and tolerability of this drug in children and adolescents ≥ 8 and ≤ 18 years of age.

Conditions: Pediatric Kidney Disease
Being tested: Envarsus®, Prograf

What participants receive

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

Envarsus®Drug
Treatment sequence: 4 weeks prolonged-release tacrolimus (Envarsus®) once daily
PrografDrug
Treatment sequence: 4 weeks intermediate-release tacrolimus (Prograf®) twice daily

Study groups in NCT06057545
Study group	Role	What they receive
Group A - Envarsus followed by Prograf	Experimental	4 weeks treatment sequence 1 (Envarsus) followed by 4 weeks treatment sequence 2 (Prograf) Receives: Drug: Envarsus®; Drug: Prograf
Group B - Prograf followed by Envarsus	Experimental	4 weeks treatment sequence 2 (Prograf) followed by 4 weeks treatment sequence 1 (Envarsus) Receives: Drug: Envarsus®; Drug: Prograf

What is being measured

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

Full tacrolimus AUC
full tacrolimus AUC calculated from Tac measures before administration of drug and 1.5, 2, 4, 6, 8, 12, 13.5, 14, 16, 20, 24 hours after administration of drug at the time point of 2 weeks (14±7 days) after end of build-up period for each patient under both treatments within two time periods with each a length of 4 weeks
Measured: 4 weeks

Secondary outcomes (11)

Pharmacodynamic analysis
Assessment of efficacy in terms of residual expression of NFAT regulated genes, expressed as % of expression at C0 (time point before drug administration set at 100%) at 1.5, 2, 4, 6, 8, 12, 13.5, 14, 16, 20, 24 hours after administration of drug at the time point of 2 weeks (14±7 days) after end of build-up period for each patient under both treatments within two time periods with each a length of 4 weeks
Measured: 4 weeks
Pharmacogenetic analysis
Number of patients with SNPs in selected genes (CYP3A4, CYP3A5, ABCD1)
Measured: 4 weeks
Tacrolimus trough levels
Tacrolimus trough levels in ng/mL, compared intra- and interindividually.
Measured: 4 weeks
Doses of prolonged-release tacrolimus
Doses of prolonged-release tacrolimus (Envarsus®) in ng/mL.
Measured: 4 weeks
Number of patients with adverse event or toxicity
Cumulative dosage and signs of tacrolimus toxicity and adverse events. Potentially tacrolimus associated adverse events and toxicity are recorded individually and compared with individual tacrolimus AUCs. Special attention is taken e.g. towards metabolic (elevated concentration of blood glucose, fat), hematopoetic (cell counts), neurological (tremor, headache), renal (change in glomerular filtration rate), gastrointestinal (diarrhea, nausea), hepatic (cholestasis, elevated transaminases, blood clotting disorder), elevated blood pressure.
Measured: 10 weeks
Number of adverse events or toxicity per patient
Special attention is taken e.g. towards metabolic (elevated concentration of blood glucose, fat), hematopoetic (cell counts), neurological (tremor, headache), renal (change in glomerular filtration rate), gastrointestinal (diarrhea, nausea), hepatic (cholestasis, elevated transaminases, blood clotting disorder), elevated blood pressure.
Measured: 10 weeks
eGFR (CKiD formula)
eGFR (CKiD formula) comparing the two study phases
Measured: 4 weeks
Treatment failure rate
composite endpoint: any patient who experienced death, graft failure, BPAR or lost to follow-up
Measured: 10 weeks
limited sampling strategy (LSS)
LSS driven 24h-AUC estimation
Measured: 4 weeks
Taxonomy of the gut microbiome
Taxonomy of the gut microbiome using metagenomic sequencing
Measured: 10 weeks
Gut microbial metabolism
Functional assessment of the gut microbiome using LC-MS based metabolomics
Measured: 10 weeks

Timeline

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

25 Apr 2023Mar 2025

First posted28 Sep 2023
Study start25 Apr 2023
Primary completionDec 2024 (estimated)
Study completionMar 2025 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Pediatric Kidney DiseaseStudies of the same condition, open and under way.
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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Model description: Multi-center, prospective, interventional, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b
Masking: None (open label)
Enrolment: 30 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06057545
Sponsor's protocol ID: Pro-Tac
Acronym: Pro-Tac
Status last verified: Sep 2023
First submitted: 24 Apr 2023
Last updated: 28 Sep 2023
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Karaterzi S, Tonshoff B, Ahlenstiel-Grunow T, Baghai M, Beck B, Buscher A, Eifler L, Giese T, Lezius S, Muller C, Oh J, Zapf A, Weber LT, Pape L. A multi-center interventional study to assess pharmacokinetics, effectiveness, and tolerability of prolonged-release tacrolimus after pediatric kidney transplantation: study protocol for a prospective, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b trial. Front Nephrol. 2024 Feb 20;4:1331510. doi: 10.3389/fneph.2024.1331510. eCollection 2024.
PubMed 38444519

Study at a glance

From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multi-center Interventional Study to Assess Pharmacokinetics, Effectiveness and Tolerability of Prolonged-release Tacrolimus After Paediatric Kidney Transplantation
ClinicalTrials.gov ID: NCT06057545
Acronym / sponsor ID: Pro-Tac / Pro-Tac
Conditions: Pediatric Kidney Disease
Phase: Phase 3
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 30 participants (estimated)
Lead sponsor: University Hospital, EssenUniversity, hospital or other
Study start: 25 Apr 2023 (actual)
Primary completion: Dec 2024 (estimated)
Study completion: Mar 2025 (estimated)
First posted: 28 Sep 2023 (actual)
Results: Not posted in the source record

Clinical summary

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

The aim of this study is to assess pharmacokinetic profiles of Envarsus® as well as effectiveness and tolerability of this drug in children and adolescents ≥ 8 and ≤ 18 years of age.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2
Model description: Multi-center, prospective, interventional, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b

Arm	Type	Receives
Group A - Envarsus followed by Prograf	Experimental	Drug: Envarsus®, Drug: Prograf4 weeks treatment sequence 1 (Envarsus) followed by 4 weeks treatment sequence 2 (Prograf)
Group B - Prograf followed by Envarsus	Experimental	Drug: Envarsus®, Drug: Prograf4 weeks treatment sequence 2 (Prograf) followed by 4 weeks treatment sequence 1 (Envarsus)

Who may qualify

Ages: 8 to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

caucasian paediatric kidney transplant recipients (single-organ recipients)
aged ≥ 8 years but ≤ 18 years who are under tacrolimus (Prograf®) therapy and who are able to swallow tablets with a minimum dose of 0.75 mg / day Envarsus®
not less than 6 months after transplantation
stable kidney function (delta eGFR < 10 ml/min/1.73 m2 (CKID formula) over the last 3 months)
women of childbearing potential and women without childbearing potential

Key exclusion criteria (7 listed)

coefficient of variation of tacrolimus trough levels > 0.35 over the previous 6 months
pregnancy/breast feeding
instable kidney function
hypersensitivity to any of the components of the medications used
not eligible for any reason according to the investigator's valuation

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
Envarsus®Treatment sequence: 4 weeks prolonged-release tacrolimus (Envarsus®) once daily	Drug	Group A - Envarsus followed by Prograf, Group B - Prograf followed by Envarsus
PrografTreatment sequence: 4 weeks intermediate-release tacrolimus (Prograf®) twice daily	Drug	Group A - Envarsus followed by Prograf, Group B - Prograf followed by Envarsus

Primary outcome

Full tacrolimus AUC
Time frame: 4 weeks
full tacrolimus AUC calculated from Tac measures before administration of drug and 1.5, 2, 4, 6, 8, 12, 13.5, 14, 16, 20, 24 hours after administration of drug at the time point of 2 weeks (14±7 days) after end of build-up period for each patient under both treatments within two time periods with each a length of 4 weeks

11 secondary outcomes

Pharmacodynamic analysis
Time frame: 4 weeks
Pharmacogenetic analysis
Time frame: 4 weeks
Tacrolimus trough levels
Time frame: 4 weeks
Doses of prolonged-release tacrolimus
Time frame: 4 weeks
Number of patients with adverse event or toxicity
Time frame: 10 weeks
Number of adverse events or toxicity per patient
Time frame: 10 weeks
eGFR (CKiD formula)
Time frame: 4 weeks
Treatment failure rate
Time frame: 10 weeks
limited sampling strategy (LSS)
Time frame: 4 weeks
Taxonomy of the gut microbiome
Time frame: 10 weeks
Gut microbial metabolism
Time frame: 10 weeks

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
Derived from this study: PubMed 38444519Karaterzi S, Tonshoff B, Ahlenstiel-Grunow T, Baghai M, Beck B, Buscher A, Eifler L, Giese T, Lezius S, Muller C, Oh J, Zapf A, Weber LT, Pape L. A multi-center interventional study to assess pharmacokinetics, effectiveness, and tolerability of prolonged-release tacrolimus after pediatric kidney transplantation: study protocol for a prospective, open-label, randomized, two-phase, two-sequence, single dose, crossover, phase III b trial. Front Nephrol. 2024 Feb 20;4:1331510. doi: 10.3389/fneph.2024.1331510. eCollection 2024.

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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.

Julia Grimm contact

+4920172377414

julia.grimm@uk-essen.de

Lars Pape, Prof. Dr. principal investigator

University Hospital of Essen, Pediatrics II

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Envarsus® and Prograf in people with Pediatric Kidney Disease, run by University Hospital, Essen at 4 sites in Germany.

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

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. 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: status not confirmed, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Germany. 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 phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Results are not available in the source record.

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

Contact Julia Grimm (+4920172377414, julia.grimm@uk-essen.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Full tacrolimus AUC (time frame: 4 weeks). 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 NCT06057545, which also lists 1 linked publication.

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 2023.