Renal ImpairmentPhase 1NCT05541159

Pharmacokinetics Study of TNO155 in Participants With Mild, Moderate, or Severe Renal Impairment Compared to Matched Healthy Participants

A Phase 1 study testing TNO155 in people with Renal Impairment, run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Trial summary

The purpose of this Phase 1 study is to evaluate the effect of various degrees of renal impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155. The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with… Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Renal Impairment
What is being tested?: TNO155
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 19 Mar 2025to 15 Jul 2025
Phase: Phase 1
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 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

All participants Participants must weigh at least 50 kg and no more than 120 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants. Must be a non-smoker or and agree to remain a non-smoker from screening until the End of Study.
Group 1
•eGFR as determined by Chronic Kidney Disease Epidemiology Collaboration [CKD EPI] equation and conversion within normal range as determined by GFR 90 mL/min at screening and baseline.
Groups 2 to 4
Participants with different levels of impaired renal function satisfying criteria for renal impairment as determined at screening by the eGFR at screening
Participants must have documented stable renal disease without evidence of renal progressive disease

Who cannot join

All Participants
Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort), within 4 weeks prior to dosing until completion of the End of Study Visit.
Participant has received a renal transplant at any time in the past and is on immunosuppressant therapy Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, at screening or baseline.
Uncontrolled hypertension despite medical treatment at screening or baseline. Group 1
Significant illness, which has not been resolved within 2 weeks prior to dosing of study treatment.
History or presence of renal disease or kidney injury Groups 2, 3 and 4

Show all 11Show fewer

Severe albuminuria
Other laboratory values grade 2 severity according to NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Participants undergoing any method of dialysis.
Participants with renal impairment due to hepatic disease (hepatorenal syndrome).
Other protocol-defined inclusion/exclusion criteria may apply

About this study

Official title: A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of TNO155 in Participants With Mild, Moderate, or Severe Renal Impairment Compared to Matched Healthy Control Participants

Read the detailed description

This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe renal impairment compared to matched healthy control participants with normal renal function. The study will be divided into 2 parts. Participants in the renal impairment groups will be staged by their respective degree of renal function (mild, moderate, or severe) according to the estimated glomerular filtration rate (eGFR) determined at the screening visit. Each renal impairment participant must be matched to a healthy control participant with respect to age (±10 years), body weight (±20%) and sex. Each participant in the healthy control group (Group 1) can be matched to one or more participants from any renal impairment group (Groups 2, 3, and 4).

On Day 1 morning, participants will receive a single oral dose of TNO155 .All participants will be domiciled from Day -1 until Day 11. All participants should have a poststudy safety follow-up contact conducted approximately 30 days after administration of study treatment. The study will be considered complete once all the participants have finished the required assessments, dropped out, or been lost to follow-up before completing the required assessments.

Conditions: Renal Impairment
Being tested: TNO155
Keywords: TNO155, renal Impairment, SHP2
Medical subject headings: Renal Insufficiency

What participants receive

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

TNO155Drug
Single oral dose of TNO155 on Day 1

Study groups in NCT05541159
Study group	Role	What they receive
Group 1	Experimental	Healthy control participants with normal renal function Receives: Drug: TNO155
Group 2	Experimental	Mild renal impairment Receives: Drug: TNO155
Group 3	Experimental	Moderate renal impairment Receives: Drug: TNO155
Group 4	Experimental	Severe renal impairment Receives: Drug: TNO155

What is being measured

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

Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
AUC from time zero to time "t" (AUC0-t) of TNO155
AUC0-t will be calculated as needed based on TNO155 plasma concentrations and non-compartmental methods. The definition of time "t" may be data-driven post-hoc to mitigate treatment bias due to within participant differences in Tlast between the treatments, or may be selected to allow between-study exposure comparisons that use a common time window.
Measured: AUC from time zero to time "t" (AUC0-t) of TNO155
AUC from time zero to infinity (AUCinf) of TNO155
AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Maximum (peak) observed plasma concentration (Cmax) of TNO155
Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Time to reach maximum observed plasma concentration (Tmax) of TNO155
Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods
Measured: Up to 240 hours post single dose
Elimination half-life (T1/2) of TNO155
T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Sampling time of the last measurable plasma concentration (Tlast) of TNO155
Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Apparent plasma clearance (CL/F) of TNO155
CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose
Apparent volume of distribution during terminal phase (Vz/F) of TNO155
Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Measured: Up to 240 hours post single dose

Secondary outcomes (8)

Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.
Measured: Up to 30 days post single dose
Unbound Cmax (Cmax,u) of TNO155
Cmax,u will be calculated based on the unbound fraction of TNO155 in plasma.
Measured: Up to 240 hours post single dose
Unbound AUClast (AUClast,u) of TNO155
AUClast,u will be calculated based on the unbound fraction of TNO155 in plasma.
Measured: Up to 240 hours post single dose
Unbound AUCinf (AUCinf,u) of TNO155
AUCinf,u will be calculated based on the unbound fraction of TNO155 in plasma
Measured: Up to 240 hours post single dose
Unbound CL/F (CL/F,u) of TNO155
CL/F,u will be calculated based on the unbound fraction of TNO155 in plasma.
Measured: Up to 240 hours post single dose
Renal clearance (CLr) of TNO155
CLr will be calculated based on urinary excretion data of TNO155.
Measured: Up to 240 hours post single dose
Apparent non-renal clearance (CLNR/F) of TNO155
CLNR/F will be calculated based on urinary excretion data of TNO155.
Measured: Up to 240 hours post single dose
Fraction of dose excreted in urine (fe) of TNO155
Fe will be calculated based on urinary excretion data of TNO155.
Measured: Up to 240 hours post single dose

Timeline

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

19 Mar 202515 Jul 2025

First posted15 Sep 2022
Study start19 Mar 2025 (estimated)
Primary completion15 Jul 2025 (estimated)
Study completion15 Jul 2025 (estimated)

Why it stopped: Sponsor's decision

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Renal ImpairmentStudies 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
Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Model description: The study will be divided into 2 parts. Participants in the renal impairment groups will be staged by their respective degree of renal function (mild, moderate, or severe) according to the estimated glomerular filtration rate determined at the screening visit. Healthy participants who were identified and enrolled as matching partners for a renal impairment group in Part I can serve as matching partners for participants in renal impairment group (Group 4) in Part II if they fulfilled the matching criteria. Otherwise, additional matched healthy participants will be enrolled. Part I: will include participants with mild and moderate levels of renal impairment as well as healthy control participants Part II: will include participants with severe renal impairment, if allowed after results of interim analysis (IA) obtained for mild and moderate groups.
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05541159
Sponsor's protocol ID: CTNO155A12105
Status last verified: Feb 2024
First submitted: 12 Sep 2022
Last updated: 29 Feb 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

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?

Official record

Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
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Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
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Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant

All Renal Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of TNO155 in Participants With Mild, Moderate, or Severe Renal Impairment Compared to Matched Healthy Control Participants
ClinicalTrials.gov ID: NCT05541159
Acronym / sponsor ID: CTNO155A12105
Conditions: Renal Impairment
Keywords: TNO155, renal Impairment, SHP2
Phase: Phase 1
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Sponsor's decision
Enrolment: 0 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Collaborators: Pharmaceutical Research Associates
Study start: 19 Mar 2025 (estimated)
Primary completion: 15 Jul 2025 (estimated)
Study completion: 15 Jul 2025 (estimated)
First posted: 15 Sep 2022 (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.

Detailed description

Study design

Primary purpose: Diagnosis
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4
Model description: The study will be divided into 2 parts. Participants in the renal impairment groups will be staged by their respective degree of renal function (mild, moderate, or severe) according to the estimated glomerular filtration rate determined at the screening visit. Healthy participants who were identified and enrolled as matching partners for a renal impairment group in Part I can serve as matching partners for participants in renal impairment group (Group 4) in Part II if they fulfilled the matching criteria. Otherwise, additional matched healthy participants will be enrolled. Part I: will include participants with mild and moderate levels of renal impairment as well as healthy control participants Part II: will include participants with severe renal impairment, if allowed after results of interim analysis (IA) obtained for mild and moderate groups.

Arm	Type	Receives
Group 1	Experimental	Drug: TNO155Healthy control participants with normal renal function
Group 2	Experimental	Drug: TNO155Mild renal impairment
Group 3	Experimental	Drug: TNO155Moderate renal impairment
Group 4	Experimental	Drug: TNO155Severe renal impairment

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

All participants Participants must weigh at least 50 kg and no more than 120 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants. Must be a non-smoker or and agree to remain a non-smoker from screening until the End of Study.
Group 1
•eGFR as determined by Chronic Kidney Disease Epidemiology Collaboration [CKD EPI] equation and conversion within normal range as determined by GFR 90 mL/min at screening and baseline.
Groups 2 to 4
Participants with different levels of impaired renal function satisfying criteria for renal impairment as determined at screening by the eGFR at screening

Key exclusion criteria (11 listed)

All Participants
Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort), within 4 weeks prior to dosing until completion of the End of Study Visit.
Participant has received a renal transplant at any time in the past and is on immunosuppressant therapy Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, at screening or baseline.
Uncontrolled hypertension despite medical treatment at screening or baseline. Group 1
Significant illness, which has not been resolved within 2 weeks prior to dosing of study treatment.

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
TNO155Single oral dose of TNO155 on Day 1	Drug	Group 1, Group 2, Group 3, Group 4

Primary outcome

Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
Time frame: Up to 240 hours post single dose
AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
AUC from time zero to time "t" (AUC0-t) of TNO155
Time frame: AUC from time zero to time "t" (AUC0-t) of TNO155
AUC0-t will be calculated as needed based on TNO155 plasma concentrations and non-compartmental methods. The definition of time "t" may be data-driven post-hoc to mitigate treatment bias due to within participant differences in Tlast between the treatments, or may be selected to allow between-study exposure comparisons that use a common time window.
AUC from time zero to infinity (AUCinf) of TNO155
Time frame: Up to 240 hours post single dose
AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Maximum (peak) observed plasma concentration (Cmax) of TNO155
Time frame: Up to 240 hours post single dose
Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time to reach maximum observed plasma concentration (Tmax) of TNO155
Time frame: Up to 240 hours post single dose
Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods
Elimination half-life (T1/2) of TNO155
Time frame: Up to 240 hours post single dose
T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Sampling time of the last measurable plasma concentration (Tlast) of TNO155
Time frame: Up to 240 hours post single dose
Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Apparent plasma clearance (CL/F) of TNO155
Time frame: Up to 240 hours post single dose
CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Apparent volume of distribution during terminal phase (Vz/F) of TNO155
Time frame: Up to 240 hours post single dose
Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.

8 secondary outcomes

Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Up to 30 days post single dose
Unbound Cmax (Cmax,u) of TNO155
Time frame: Up to 240 hours post single dose
Unbound AUClast (AUClast,u) of TNO155
Time frame: Up to 240 hours post single dose
Unbound AUCinf (AUCinf,u) of TNO155
Time frame: Up to 240 hours post single dose
Unbound CL/F (CL/F,u) of TNO155
Time frame: Up to 240 hours post single dose
Renal clearance (CLr) of TNO155
Time frame: Up to 240 hours post single dose
Apparent non-renal clearance (CLNR/F) of TNO155
Time frame: Up to 240 hours post single dose
Fraction of dose excreted in urine (fe) of TNO155
Time frame: Up to 240 hours post single dose

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
Individual participant dataSharing planned: No

Related trials for Renal Impairment

Active, not recruitingPhase 2
Safety and Efficacy of Empagliflozin in Hemodialysis
End Stage Renal Disease
RecruitingPhase 3
Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Atrasentan in Pediatric Patients With Primary IgAN
Berger Disease, Bergers Disease
Recruiting
NightWare and Cardiovascular Health in Women With PTSD
Post Traumatic Stress Disorder, Cardiovascular Diseases
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TNO155 in people with Renal Impairment, run by Novartis Pharmaceuticals.

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 6 inclusion and 11 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: withdrawn, as of the sponsor's last update on 29 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155 (time frame: Up to 240 hours post single dose). The study lists 9 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 NCT05541159.

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 29 Feb 2024.