Healthy SubjectsPhase 1NCT03463044
Safety, Tolerability and Pharmacokinetic Profiles of MOTREM (LR12) in Healthy Male Subjects
A Phase 1 study testing nangibotide in people with Healthy Subjects, run by Inotrem at 1 site in United Kingdom.
Trial summary
This was a single center, randomized, placebo-controlled study with a sequential i.v. dose escalation cohorts design, to assess safety, tolerability and pharmacokinetics of MOTREM (nangibotide) in healthy volunteers Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects
- What is being tested?
- nangibotide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2016to 25 Aug 2016
- Phase
- Phase 1
- 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 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy male
- ≥18 to ≤45 years old
- Body mass index (BMI) between 18-30 kg/m² inclusive
- Written informed consent to participate.
- Main Exclusion Criteria:
- Any clinically relevant acute or chronic diseases
- Any history of drug or alcohol abuse
- Any History of clinical significant disease as determined by medical history, physical examination or other evaluations.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomised, Placebo Controlled Study to Assess the Safety, Tolerability and Pharmacokinetic Profiles of Ascending, Single, Intravenous Doses of MOTREM (LR12) in Healthy Male Subjects
This was a single center, randomized, placebo-controlled study with a sequential i.v. dose escalation cohorts design, to assess safety, tolerability and pharmacokinetics of MOTREM (nangibotide) in healthy volunteers
Read the detailed description
This was a dose escalation study in healthy volunteers to evaluate the safety and pharmacokinetics of nangibotide in humans
- Conditions
- Healthy Subjects
- Being tested
- nangibotide, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nangibotideDrug
Also called LR12, MOTREM
Continous i.v. infusion
PlaceboDrug
Also called matched placebo
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Matched placebo Receives: Drug: Placebo |
| MOTREM 1 | Experimental | nangibotide dose 1 Receives: Drug: nangibotide |
| MOTREM 2 | Experimental | Nangibotide dose 2 Receives: Drug: nangibotide |
| MOTREM 3 | Experimental | Nangibotide dose 3 Receives: Drug: nangibotide |
| MOTREM 4 | Experimental | Nangibotide dose 4 Receives: Drug: nangibotide |
| MOTREM 5 | Experimental | Nangibotide dose 5 Receives: Drug: nangibotide |
| MOTREM 6 | Experimental | Nangibotide dose 6 Receives: Drug: nangibotide |
| MOTREM 7 | Experimental | Nangibotide dose 7 Receives: Drug: nangibotide |
| MOTREM 8 | Experimental | Nangibotide dose 8 Receives: Drug: nangibotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability: the Number of Subjects Experiencing Treatment Emergent Adverse Events
The number of subjects experiencing treatment emergent adverse events was collected to assess the safety and tolerability of MOTREM (LR12) in comparison with placebo.
Measured: 30-44 days
Secondary outcomes (9)
Pharmacokinetics (Maximum Plasma Concentration)
Plasma concentrations of LR12 were measured by a validated liquid chromatography-mass spectrometry (LC-MS/MS) assay and analyzed using noncompartmental methods to obtain estimates of the pharmacokinetic parameter of Maximum Plasma Concentration (Cmax).
Measured: Maximum Plasma Concentration (Cmax) was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cmax is determined over a period of time starting from predose to 10h after start of the loading dose.
Statistical Analysis of LR12 PK Parameters: Steady State Concentration During the Maintenance Infusion (Cavg30-465)
Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of steady state concentration during the maintenance infusion (Cavg30-465).
Measured: Cavg30-465 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cavg30-465 is determined over a period of time starting from predose to 10h after start of the loading dose.
Statistical Analysis of LR12 PK Parameters: t1/2
Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of terminal half-life (t1/2).
Of note, apparent increase in half-life at increasing doses is explained by the detection of a slow elimination phase, which was below limit of quantification for the lower doses.
Measured: t1/2 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t1/2 is determined over a period of time starting from 7 h and 45 min to 10h after start of the loading dose (decaying period).
Statistical Analysis of LR12 PK Parameters: AUC0-t
Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of the area under the plasma concentration curve (h.ng/mL) from time zero (predose) to the time of last observed concentration (t) measured (which can go up to 10h post loading dose start) using a linear trapezoidal method (AUC0-t).
Measured: AUC0-t was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-t is determined over a period of time starting time zero (predose) to the time of last observed concentration (t).
Statistical Analysis of LR12 PK Parameters: AUC0-∞
Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of AUC0-∞.
AUC0-∞ represents the area under the plasma concentration-time curve (h.ng/mL) from time 0 to infinity (AUC0- ∞= AUC0-t + [Ct/ke], where Ct = the observed concentration of drug for the last sample on the PK profile in which drug was detected, and ke represents the terminal rate constant). The percentage of extrapolation of AUC0-∞ should not exceed 20%.
Measured: AUC0-∞ was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-∞ is determined over a period of time starting time zero (predose) to infinity (cf. extrapolation formula in the above section).
Statistical Analysis of LR12 PK Parameters: CL
Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analyzed using noncompartmental methods to obtain estimates of the PK parameter of systemic clearance (CL). The systemic clearance was estimated using the formula: CL = K0/ Css where K0 is the perfusion rate (ng/kg/h) and Css is the concentration at the end of perfusion (C at 465 min).
Of note, this narrow range of the clearance values indicates that the apparent increases in t1/2 and volume of distribution as a function of doses are not due to a non-linearity in the pharmacokinetics, but to the limit of quantification of the bioanalytical assay.
Measured: CL was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min (465 min). CL is calculated based on the perfusion rate (ng/kg/h) and the concentration at the end of perfusion (7h45min = 465min).
Statistical Analysis of LR12 PK Parameters: Volume of Distribution (V)
The volume of distribution was estimated according to the following equation: V= CL x MRT (mean residence time). However, regarding administration procedures, MRT could not be calculated precisely. Furthermore, in some cases MRT could not be estimated. Thus, the following formula was used V = CL / ke.
The terminal rate constant (ke) was estimated by log-linear regression analysis on data points visually assessed to be on the terminal log-linear phase.
Of note, it can be said that this apparent increase in V is also explained by the detection of a slow elimination phase, which was below limit of quantification for the lower doses.
Measured: V was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. V is derived from both CL and ke which are calculated from the LR12 concentration time curve from predose to 10h after loading dose start.
Statistical Analysis of LR12 PK Parameters: Tmax
Plasma concentrations of LR12 were measured by a validated LC-MS/MS assay and analysed using noncompartmental methods to obtain estimates of the PK parameter of the time at which Cmax is apparent, identified by inspection of the plasma drug concentration vs.time data by WinNonlin (tmax).
Measured: tmax was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. tmax is determined over a period of time starting from predose to 10h after start of the loading dose.
Statistical Analysis of LR12 PK Parameters: t Last
This PK parameter was calculated from measured plasma concentrations of LR12 and it represents the time of last observed concentration.
Measured: t last was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t last is determined as the time of last observed concentration which can go up to 10h after loading dose start.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2018
- Study start1 Apr 2016
- Primary completion25 Aug 2016
- Study completion25 Aug 2016
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy SubjectsStudies 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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inotrem
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Richmond Pharmacology Limited
- Responsible party
- Sponsor
- Investigators
- Valérie Cuvier, Study director, Inotrem
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03463044
- Sponsor's protocol ID
- MOT-C-104
- Status last verified
- Jan 2025
- First submitted
- 27 Feb 2018
- Last updated
- 10 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Cuvier V, Lorch U, Witte S, Olivier A, Gibot S, Delor I, Garaud JJ, Derive M, Salcedo-Magguilli M. A first-in-man safety and pharmacokinetics study of nangibotide, a new modulator of innate immune response through TREM-1 receptor inhibition. Br J Clin Pharmacol. 2018 Oct;84(10):2270-2279. doi: 10.1111/bcp.13668. Epub 2018 Jul 20.
PubMed 29885068
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomised, Placebo Controlled Study to Assess the Safety, Tolerability and Pharmacokinetic Profiles of Ascending, Single, Intravenous Doses of MOTREM (LR12) in Healthy Male Subjects
- ClinicalTrials.gov ID
- NCT03463044
- Acronym / sponsor ID
- MOT-C-104
- Conditions
- Healthy Subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- InotremIndustry (pharma, biotech, devices)
- Collaborators
- Richmond Pharmacology Limited
- Study start
- 1 Apr 2016 (actual)
- Primary completion
- 25 Aug 2016 (actual)
- Study completion
- 25 Aug 2016 (actual)
- First posted
- 13 Mar 2018 (actual)
- Results
- Posted 10 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a single center, randomized, placebo-controlled study with a sequential i.v. dose escalation cohorts design, to assess safety, tolerability and pharmacokinetics of MOTREM (nangibotide) in healthy volunteers
Detailed description
This was a dose escalation study in healthy volunteers to evaluate the safety and pharmacokinetics of nangibotide in humans
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo |
| MOTREM 1 | Experimental | Drug: nangibotidenangibotide dose 1 |
| MOTREM 2 | Experimental | Drug: nangibotideNangibotide dose 2 |
| MOTREM 3 | Experimental | Drug: nangibotideNangibotide dose 3 |
| MOTREM 4 | Experimental | Drug: nangibotideNangibotide dose 4 |
| MOTREM 5 | Experimental | Drug: nangibotideNangibotide dose 5 |
| MOTREM 6 | Experimental | Drug: nangibotideNangibotide dose 6 |
| MOTREM 7 | Experimental | Drug: nangibotideNangibotide dose 7 |
| MOTREM 8 | Experimental | Drug: nangibotideNangibotide dose 8 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- healthy male
- ≥18 to ≤45 years old
- Body mass index (BMI) between 18-30 kg/m² inclusive
- Written informed consent to participate.
- Any clinically relevant acute or chronic diseases
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| nangibotideAlso: LR12, MOTREMContinous i.v. infusion | Drug | MOTREM 1, MOTREM 2, MOTREM 3, MOTREM 4, MOTREM 5, MOTREM 6, MOTREM 7, MOTREM 8 |
| PlaceboAlso: matched placeboPlacebo | Drug | Placebo |
Primary outcome
Safety and Tolerability: the Number of Subjects Experiencing Treatment Emergent Adverse Events
Time frame: 30-44 days
The number of subjects experiencing treatment emergent adverse events was collected to assess the safety and tolerability of MOTREM (LR12) in comparison with placebo.
9 secondary outcomes
Pharmacokinetics (Maximum Plasma Concentration)
Time frame: Maximum Plasma Concentration (Cmax) was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cmax is determined over a period of time starting from predose to 10h after start of the loading dose.
Statistical Analysis of LR12 PK Parameters: Steady State Concentration During the Maintenance Infusion (Cavg30-465)
Time frame: Cavg30-465 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. Cavg30-465 is determined over a period of time starting from predose to 10h after start of the loading dose.
Statistical Analysis of LR12 PK Parameters: t1/2
Time frame: t1/2 was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t1/2 is determined over a period of time starting from 7 h and 45 min to 10h after start of the loading dose (decaying period).
Statistical Analysis of LR12 PK Parameters: AUC0-t
Time frame: AUC0-t was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-t is determined over a period of time starting time zero (predose) to the time of last observed concentration (t).
Statistical Analysis of LR12 PK Parameters: AUC0-∞
Time frame: AUC0-∞ was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. AUC0-∞ is determined over a period of time starting time zero (predose) to infinity (cf. extrapolation formula in the above section).
Statistical Analysis of LR12 PK Parameters: CL
Time frame: CL was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min (465 min). CL is calculated based on the perfusion rate (ng/kg/h) and the concentration at the end of perfusion (7h45min = 465min).
Statistical Analysis of LR12 PK Parameters: Volume of Distribution (V)
Time frame: V was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. V is derived from both CL and ke which are calculated from the LR12 concentration time curve from predose to 10h after loading dose start.
Statistical Analysis of LR12 PK Parameters: Tmax
Time frame: tmax was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. tmax is determined over a period of time starting from predose to 10h after start of the loading dose.
Statistical Analysis of LR12 PK Parameters: t Last
Time frame: t last was assessed only for Groups 3-8 who received loading dose over 15 min and maintenance dose over 7 h and 45 min. t last is determined as the time of last observed concentration which can go up to 10h after loading dose start.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29885068Cuvier V, Lorch U, Witte S, Olivier A, Gibot S, Delor I, Garaud JJ, Derive M, Salcedo-Magguilli M. A first-in-man safety and pharmacokinetics study of nangibotide, a new modulator of innate immune response through TREM-1 receptor inhibition. Br J Clin Pharmacol. 2018 Oct;84(10):2270-2279. doi: 10.1111/bcp.13668. Epub 2018 Jul 20.
- Individual participant dataSharing planned: No
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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.
Valérie Cuvier study director
Inotrem
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing nangibotide in people with Healthy Subjects, run by Inotrem at 1 site in United Kingdom.
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 8 inclusion and 0 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 10 Feb 2025. 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 United Kingdom. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 10 Feb 2025). 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?
Safety and Tolerability: the Number of Subjects Experiencing Treatment Emergent Adverse Events (time frame: 30-44 days). 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 NCT03463044, 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 10 Feb 2025.