Nontuberculous Mycobacterial DiseasesPhase 2C-LOADNCT05294146
Pharmacokinetic Study With a Loading Dose of Clofazimine in Adult Patients With Nontuberculous Mycobacterial Disease
A Phase 2 study testing Clofazimine in people with Nontuberculous Mycobacterial Diseases, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
Clofazimine (CFZ) is a promising drug for the treatment of NTM diseases. CFZ is highly active in vitro against M. abscessus and M. avium, the most common NTM pathogens, and shows synergy with macrolides and amikacin. The results from limited clinical studies with CFZ-based treatment regimens are promising. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nontuberculous Mycobacterial Diseases
- What is being tested?
- Clofazimine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteNetherlands
- Study dates
- 14 Feb 2022to 8 Aug 2023
- Phase
- Phase 2
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The participant is diagnosed with pulmonary or extrapulmonary NTM disease and is eligible for treatment with CFZ
- The participant is at least 18 years of age
- The participant has a body weight (in light clothing and with no shoes) of at least 45 kg
- The participant is able and willing to provide written, informed consent
Who cannot join
- The participant is in poor general condition where participation in the study cannot be accepted per discretion of the Investigator
- There is evidence showing the participant has clinically significant metabolic, gastrointestinal, or other abnormalities that could possibly alter the PK of CFZ
- The participant is diagnosed with cystic fibrosis
- The participant has a prolongation of the QTc interval, > 450 milliseconds for males and > 460 milliseconds for females, on the screening ECG
- The participant has abnormal alanine aminotransferase (ALT) and/or aspartate transferase (AST) levels of > 3 times the upper limit of the laboratory reference range at screening
- The participant is pregnant or is using inadequate contraceptive measures (if applicable)
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- The participant is breastfeeding (if applicable)
- The participant has a known or suspected, current drug or alcohol abuse, that is, in the opinion of the Investigator, sufficient to compromise the safety or cooperation of the patient
- The participant has as history of allergy/hypersensitivity to CFZ
- The participant has received clofazimine in the past 3 months before inclusion with the exception of short-term use of no more than 7 days in the period of 1 to 3 months before inclusion
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud university medical center
Nijmegen, Gelderland, 6525 GA
About this study
Clofazimine (CFZ) is a promising drug for the treatment of NTM diseases. CFZ is highly active in vitro against M. abscessus and M. avium, the most common NTM pathogens, and shows synergy with macrolides and amikacin. The results from limited clinical studies with CFZ-based treatment regimens are promising. CFZ is currently considered an alternative drug for patients with M. avium complex infections, who are intolerant of first-line drugs. CFZ is a first-line oral drug for treatment of M. abscessus infections.
CFZ might prove to be a cornerstone in NTM treatment, but its optimal dosage is not known. The current dose for adults is 100 mg oncedaily. However, due to the complex pharmacokinetics (PK) of CFZ - it is highly protein bound, extremely lipophilic and accumulates in fatty tissues resulting in a long elimination half-life of ~30 days - it takes several months before steady state, and presumably effective, concentrations are achieved. With the use of a loading dose regimen concentrations similar to those at steady state could be reached faster, possibly leading to improved early treatment efficacy.
Read more
The overarching aim of this study is to contribute to dose optimization of CFZ in the treatment of NTM diseases. It will be an explorative, single-center, one-arm, open label, pharmacokinetic study. A number of 10 patients with pulmonary or extrapulmonary NTM disease will be included. Patients will receive a loading dose regimen of 300 mg once daily for 4 weeks and will then continue with a standard dose of 100 mg once daily until a total 4 months of treatment with CFZ.
The primary objective of this study is to describe the PK of CFZ, after 4 weeks of treatment with a loading dose regimen of 300 mg once daily, in adult patients with pulmonary or extrapulmonary NTM disease
- Conditions
- Nontuberculous Mycobacterial Diseases
- Being tested
- Clofazimine
- Keywords
- Pulmonary and extrapulmonary NTM diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ClofazimineDrug
Also called Lamprene
All participants will receive an (experimental) oral loading dose regimen of 300 mg clofazimine once daily (= 3 capsules of 100 mg) for 4 weeks. Afterwards, all participants will continue with a standard oral dose of 100 mg clofazimine once daily (= 1 capsule of 100 mg) until a total 4 months of treatment with CFZ.
Blood samples will be taken at Day 28 (+/- 2 days), Day 29 (Day 28 +1) and after 4 months of treatment to assess the pharmacokinetics of CFZ, both with the loading dose and the standard dose. In addition, the safety/tolerability of CFZ will monitored.
| Study group | Role | What they receive |
|---|---|---|
| Loading dose Clofazimine | Experimental | All participants will receive an (experimental) oral loading dose regimen of 300 mg clofazimine (CFZ) once daily (= 3 capsules of 100 mg) for 4 weeks. Afterwards, all participants will continue with a standard oral dose of 100 mg clofazimine once daily (= 1 capsule of 100 mg) until a total 4 months of treatment with CFZ. Receives: Drug: Clofazimine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameters of clofazimine after a loading dose regimen (1)
The area under the curve (AUC0-24), after a loading dose regimen of 300 mg once daily for 4 weeks in adult patients with pulmonary or extrapulmonary NTM disease.
Measured: 24 hours sampling at Day 28 (+/- 2 days)
Pharmacokinetic parameters of clofazimine after a loading dose regimen (2)
The peak plasma concentration (Cmax), after a loading dose regimen of 300 mg once daily for 4 weeks in adult patients with pulmonary or extrapulmonary NTM disease.
Measured: 24 hours sampling at Day 28 (+/- 2 days)
Pharmacokinetic parameters of clofazimine after a loading dose regimen (3)
The plasma trough concentration (Cmin), after a loading dose regimen of 300 mg once daily for 4 weeks in adult patients with pulmonary or extrapulmonary NTM disease.
Measured: 24 hours sampling at Day 28 (+/- 2 days)
Secondary outcomes (6)
Difference between the highest measured concentrations of CFZ in this study and a reference study
Difference between the highest measured concentrations of CFZ in this study and a reference study (PERC study; EudraCT number 2015-003786-28) after approximately 1 and 4 months of treatment.
Measured: After approximately 1 and 4 months of treatment
The predicted time (e.g. weeks) needed to reach steady state concentrations with and without a loading dose
Based on the PK parameters in this study and a reference study (PERC study; EudraCT number 2015-003786-28), the time (in weeks or months) that is needed to reach steady concentrations will be predicted. This will be done for both the loading dose regimen and for a standard dose regimen (i.e. the current clinical care). The goal is to assess how much faster steady state concentrations are reached with a loading dose regimen compared to the standard dose.
Measured: Expected: 1 to 4 months
Predicted PK parameters (1)
The predicted area under the curve (AUC0-24), after approximately 1 and 4 months of treatment in both this study and a reference study (PERC study; EudraCT number 2015-003786-28)
Measured: After approximately 1 and 4 months of treatment
Predicted PK parameters (2)
The predicted peak concentration (Cmax), after approximately 1 and 4 months of treatment in both this study and a reference study (PERC study; EudraCT number 2015-003786-28)
Measured: After approximately 1 and 4 months of treatment
Predicted PK parameters (3)
The predicted trough concentration (C0), after approximately 1 and 4 months of treatment in both this study and a reference study (PERC study; EudraCT number 2015-003786-28)
Measured: After approximately 1 and 4 months of treatment
Adverse Events
The number of (participants with) adverse events will be measured. Adverse events will be graded according to the 'Common Terminology Criteria for Adverse Events' (CTCAE)
Measured: Through study completion, a period of 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2022
- Study start14 Feb 2022
- Primary completion1 May 2023
- Study completion8 Aug 2023
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 Nontuberculous Mycobacterial DiseasesStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe 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 2
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- All participants will receive a loading dose regimen of 300 mg clofazimine (CFZ) once daily for 4 weeks and will then continue with a standard dose of 100 mg CFZ once daily until a total 4 months of treatment with CFZ.
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prof. dr. R.E. Aarnoutse, PharmD, PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05294146
- Sponsor's protocol ID
- C-LOAD
- Acronym
- C-LOAD
- Status last verified
- Sep 2022
- First submitted
- 1 Mar 2022
- Last updated
- 16 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Stemkens R, Lemson A, Koele SE, Svensson EM, Te Brake LHM, van Crevel R, Boeree MJ, Hoefsloot W, van Ingen J, Aarnoutse RE. A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease. J Antimicrob Chemother. 2024 Dec 2;79(12):3100-3108. doi: 10.1093/jac/dkae309.
PubMed 39378281
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Study With a Loading Dose of Clofazimine in Adult Patients With Nontuberculous Mycobacterial Disease
- ClinicalTrials.gov ID
- NCT05294146
- Acronym / sponsor ID
- C-LOAD / C-LOAD
- Conditions
- Nontuberculous Mycobacterial Diseases
- Keywords
- Pulmonary and extrapulmonary NTM diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 14 Feb 2022 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 8 Aug 2023 (actual)
- First posted
- 24 Mar 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.
Clofazimine (CFZ) is a promising drug for the treatment of NTM diseases. CFZ is highly active in vitro against M. abscessus and M. avium, the most common NTM pathogens, and shows synergy with macrolides and amikacin. The results from limited clinical studies with CFZ-based treatment regimens are promising. CFZ is currently considered an alternative drug for patients with M. avium complex infections, who are intolerant of first-line drugs. CFZ is a first-line oral drug for treatment of M. abscessus infections.
CFZ might prove to be a cornerstone in NTM treatment, but its optimal dosage is not known. The current dose for adults is 100 mg oncedaily. However, due to the complex pharmacokinetics (PK) of CFZ - it is highly protein bound, extremely lipophilic and accumulates in fatty tissues resulting in a long elimination half-life of ~30 days - it takes several months before steady state, and presumably effective, concentrations are achieved. With the use of a loading dose regimen concentrations similar to those at steady state could be reached faster, possibly leading to improved early treatment efficacy.
The overarching aim of this study is to contribute to dose optimization of CFZ in the treatment of NTM diseases. It will be an explorative, single-center, one-arm, open label, pharmacokinetic study. A number of 10 patients with pulmonary or extrapulmonary NTM disease will be included. Patients will receive a loading dose regimen of 300 mg once daily for 4 weeks and will then continue with a standard dose of 100 mg once daily until a total 4 months of treatment with CFZ.
The primary objective of this study is to describe the PK of CFZ, after 4 weeks of treatment with a loading dose regimen of 300 mg once daily, in adult patients with pulmonary or extrapulmonary NTM disease
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants will receive a loading dose regimen of 300 mg clofazimine (CFZ) once daily for 4 weeks and will then continue with a standard dose of 100 mg CFZ once daily until a total 4 months of treatment with CFZ.
| Arm | Type | Receives |
|---|---|---|
| Loading dose Clofazimine | Experimental | Drug: ClofazimineAll participants will receive an (experimental) oral loading dose regimen of 300 mg clofazimine (CFZ) once daily (= 3 capsules of 100 mg) for 4 weeks. Afterwards, all participants will continue with a standard oral dose of 100 mg clofazimine once daily (= 1 capsule of 100 mg) until a total 4 months of treatment with CFZ. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- The participant is diagnosed with pulmonary or extrapulmonary NTM disease and is eligible for treatment with CFZ
- The participant is at least 18 years of age
- The participant has a body weight (in light clothing and with no shoes) of at least 45 kg
- The participant is able and willing to provide written, informed consent
Key exclusion criteria (10 listed)
- The participant is in poor general condition where participation in the study cannot be accepted per discretion of the Investigator
- There is evidence showing the participant has clinically significant metabolic, gastrointestinal, or other abnormalities that could possibly alter the PK of CFZ
- The participant is diagnosed with cystic fibrosis
- The participant has a prolongation of the QTc interval, > 450 milliseconds for males and > 460 milliseconds for females, on the screening ECG
- The participant has abnormal alanine aminotransferase (ALT) and/or aspartate transferase (AST) levels of > 3 times the upper limit of the laboratory reference range at screening
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 |
|---|---|---|
| ClofazimineAlso: LampreneAll participants will receive an (experimental) oral loading dose regimen of 300 mg clofazimine once daily (= 3 capsules of 100 mg) for 4 weeks. Afterwards, all participants will continue with a standard oral dose of 100 mg clofazimine once daily (= 1 capsule of 100 mg) until a total 4 months of treatment with CFZ. Blood samples will be taken at Day 28 (+/- 2 days), Day 29 (Day 28 +1) and after 4 months of treatment to assess the pharmacokinetics of CFZ, both with the loading dose and the standard dose. In addition, the safety/tolerability of CFZ will monitored. | Drug | Loading dose Clofazimine |
Primary outcome
Pharmacokinetic parameters of clofazimine after a loading dose regimen (1)
Time frame: 24 hours sampling at Day 28 (+/- 2 days)
The area under the curve (AUC0-24), after a loading dose regimen of 300 mg once daily for 4 weeks in adult patients with pulmonary or extrapulmonary NTM disease.
Pharmacokinetic parameters of clofazimine after a loading dose regimen (2)
Time frame: 24 hours sampling at Day 28 (+/- 2 days)
The peak plasma concentration (Cmax), after a loading dose regimen of 300 mg once daily for 4 weeks in adult patients with pulmonary or extrapulmonary NTM disease.
Pharmacokinetic parameters of clofazimine after a loading dose regimen (3)
Time frame: 24 hours sampling at Day 28 (+/- 2 days)
The plasma trough concentration (Cmin), after a loading dose regimen of 300 mg once daily for 4 weeks in adult patients with pulmonary or extrapulmonary NTM disease.
6 secondary outcomes
Difference between the highest measured concentrations of CFZ in this study and a reference study
Time frame: After approximately 1 and 4 months of treatment
The predicted time (e.g. weeks) needed to reach steady state concentrations with and without a loading dose
Time frame: Expected: 1 to 4 months
Predicted PK parameters (1)
Time frame: After approximately 1 and 4 months of treatment
Predicted PK parameters (2)
Time frame: After approximately 1 and 4 months of treatment
Predicted PK parameters (3)
Time frame: After approximately 1 and 4 months of treatment
Adverse Events
Time frame: Through study completion, a period of 4 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2023.
- Derived from this study: PubMed 39378281Stemkens R, Lemson A, Koele SE, Svensson EM, Te Brake LHM, van Crevel R, Boeree MJ, Hoefsloot W, van Ingen J, Aarnoutse RE. A loading dose of clofazimine to rapidly achieve steady-state-like concentrations in patients with nontuberculous mycobacterial disease. J Antimicrob Chemother. 2024 Dec 2;79(12):3100-3108. doi: 10.1093/jac/dkae309.
- Individual participant dataSharing planned: Undecided
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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.
Prof. dr. R.E. Aarnoutse, PharmD, PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Clofazimine in people with Nontuberculous Mycobacterial Diseases, run by Radboud University Medical Center at 1 site in Netherlands.
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 4 inclusion and 10 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: finished, as of the sponsor's last update on 16 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pharmacokinetic parameters of clofazimine after a loading dose regimen (1) (time frame: 24 hours sampling at Day 28 (+/- 2 days)). The study lists 3 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 NCT05294146, 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 16 Aug 2023.