Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2017-000290-37 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is an open label, uncontrolled, Phase 4 study including 10 patients who present in hospital/urgent care setting with acquired methemoglobinemia. The population may include pediatric and adult patients (males and females of all ages are included).
The study will run in both the EU and the US. The aim of the study is to confirm safety and efficacy of ProvayBlueTM for the treatment of acquired methemoglobinemia and has been requested by the US-FDA as a Post-Marketing requirements.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ProvayBlue (Methylene Blue) arm | Experimental | Methylene Blue 0.5% will be administered. 1 mg/kg will be administered intravenously over 5-30 minutes. If methemoglobin level remains above 30% or if clinical symptoms persist, give a repeat dose of up to 1 mg/kg one hour after the first dose. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylene Blue | Drug | Administration of Methylene Blue to treat acquired methaemoglobinaemia |
|
| Measure | Description | Time Frame |
|---|---|---|
| Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level | A 50% reduction in metHb level within 1 hour of the first dose of ProvayBlue for treatment of acquired methemoglobinemia. The timing of postdosing metHb level assays is inconsistent in clinical practice, for that reason metHb level at 1-hour postdosing was derived using linear interpolation. | 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With and Without Concomitant Normalization of Respiratory Rate | Normalization of the respiratory rate within 2 hours of the first dose of ProvayBlue. The normal range used for respiratory rate was 12-20 breaths per minute. | 2 hours |
| Number of Participants With and Without Concomitant Normalization of Heart Rate |
Not provided
Inclusion Criteria:
Acquired methemoglobinemia is defined as a level of methemoglobinemia >30% or ≤30% in case of clinical symptoms (e.g. sleepiness, cyanosis, dizziness, etc.).
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Bruno Megarbane | Hopital Lariboisière | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Lariboisière | Paris | 75475 | France |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Recruitment period was from July 2018- August 2020. There were 13 hospital/urgent care sites initiated in France, the United Kingdom (UK), and the United States (US).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | ProvayBlue (Methylene Blue) Arm | Methylene Blue 0.5% will be administered. 1 mg/kg will be administered intravenously over 5-30 minutes. If methemoglobin level remains above 30% or if clinical symptoms persist, give a repeat dose of up to 1 mg/kg one hour after the first dose. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | ProvayBlue (Methylene Blue) Arm | Methylene Blue 0.5% will be administered. 1 mg/kg will be administered intravenously over 5-30 minutes. If methemoglobin level remains above 30% or if clinical symptoms persist, give a repeat dose of up to 1 mg/kg one hour after the first dose. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Primary Efficacy Endpoint: Number of Participants With and Without 50% Reduction in metHb Level | A 50% reduction in metHb level within 1 hour of the first dose of ProvayBlue for treatment of acquired methemoglobinemia. The timing of postdosing metHb level assays is inconsistent in clinical practice, for that reason metHb level at 1-hour postdosing was derived using linear interpolation. | The efficacy analysis set includes all safety analysis set patients who have at least 1 metHb assessment before and after ProvayBlue infusion | Posted | Count of Participants | Participants | 1 hour |
|
AEs reported after the first dose infusion start time and within 10 days after the last dose treatment were collected.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ProvayBlue (Methylene Blue) Arm | Methylene Blue 0.5% will be administered. 1 mg/kg will be administered intravenously over 5-30 minutes. If methemoglobin level remains above 30% or if clinical symptoms persist, give a repeat dose of up to 1 mg/kg one hour after the first dose. Methylene Blue: Administration of Methylene Blue to treat acquired methaemoglobinaemia |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombosis | Vascular disorders | MedDRA (23.0) | Non-systematic Assessment | lower limb thrombosis [right femoral vein + left fibular vein] |
Not provided
This study experienced a slow pace of enrollment leading to enrollment being closed prior to completing enrollment of the planned sample size of 10 subjects. Additionally, the nature of the disease and indication, necessitated that the subject's treatment with ProvayBlue was per the investigator's standard care and could have occurred prior to or after the PICD was signed. This frequently prevented the collection of pharmacokinetic (PK) blood draws and study specific evaluations on schedule.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Emilie HUYGHUES | Provepharm SAS | +33 6 20 58 28 27 | emilie.huyghues@provepharm.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 10, 2017 | Mar 15, 2023 | Prot_004.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 30, 2021 | Feb 15, 2023 | SAP_003.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D008751 | Methylene Blue |
| ID | Term |
|---|---|
| D010640 | Phenothiazines |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D006575 | Heterocyclic Compounds, 3-Ring |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Normalization of the heart rate within 2 hours of the first dose of ProvayBlue. The normal range used for heart rate was 50-100 beats per minute. |
| 2 hours |
| Number of Participants With and Without Concomitant Normalization of Blood Pressure | Normalization of blood pressure standard values within 2 hours of the first dose of ProvayBlue. The normal range used for systolic blood pressure was was 90-140 mm HG and the normal range used for diastolic blood pressure was 60-90 mm HG. | 2 hours |
| Second Dose | Evaluation of the patients who achieve a 50% reduction in metHb level after a second dose of ProvayBlue | 1 hour |
| Number of Participants With Treatment-related Adverse Events | Number of participants who experience a treatment emergent adverse event assessed by the investigator as being related to study drug.. | 24 hours |
| Methylene Blue Content in Blood Samples | Blood samples will be analyzed for methylene blue content | 24 hours |
| Azure B Content in Blood Samples | Blood samples will be analyzed for Azure B content | 24 hours |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Baseline methemoglobin | Percentage of methemoglobin in blood | One patient did not have a baseline methemoglobin result. | Mean | Standard Deviation | percentage of methemoglobin in blood |
|
|
|
| Secondary | Number of Participants With and Without Concomitant Normalization of Respiratory Rate | Normalization of the respiratory rate within 2 hours of the first dose of ProvayBlue. The normal range used for respiratory rate was 12-20 breaths per minute. | All Patients who received study drug | Posted | Count of Participants | Participants | 2 hours |
|
|
|
| Secondary | Number of Participants With and Without Concomitant Normalization of Heart Rate | Normalization of the heart rate within 2 hours of the first dose of ProvayBlue. The normal range used for heart rate was 50-100 beats per minute. | All participants who received study drug | Posted | Count of Participants | Participants | 2 hours |
|
|
|
| Secondary | Number of Participants With and Without Concomitant Normalization of Blood Pressure | Normalization of blood pressure standard values within 2 hours of the first dose of ProvayBlue. The normal range used for systolic blood pressure was was 90-140 mm HG and the normal range used for diastolic blood pressure was 60-90 mm HG. | All participants who received a dose of study drug | Posted | Count of Participants | Participants | 2 hours |
|
|
|
| Secondary | Second Dose | Evaluation of the patients who achieve a 50% reduction in metHb level after a second dose of ProvayBlue | Only 1 patient received a second dose of ProvayBlue and they did not have a metHb measurement within 1 hour of that second dose | Posted | 1 hour |
|
|
| Secondary | Number of Participants With Treatment-related Adverse Events | Number of participants who experience a treatment emergent adverse event assessed by the investigator as being related to study drug.. | All participants who received at least one dose of study drug | Posted | Count of Participants | Participants | 24 hours |
|
|
|
| Secondary | Methylene Blue Content in Blood Samples | Blood samples will be analyzed for methylene blue content | Due to the nature of the disease, treatment with ProvayBlue was per the investigator's standard care and may have occurred prior to the informed consent document (PICD) being signed. However, data collection and study-specific assessments were to take place only after ICD signature. This often prevented collection of pharmacokinetic (PK) blood draws as informed consent was often given after the blood draws were to have been completed. As a result there were no patients with evaluable PK data. | Posted | 24 hours |
|
|
| Secondary | Azure B Content in Blood Samples | Blood samples will be analyzed for Azure B content | Due to the nature of the disease, treatment with ProvayBlue was per the investigator's standard care and may have occurred prior to the informed consent document (PICD) being signed. However, data collection and study-specific assessments were to take place only after ICD signature. This often prevented collection of pharmacokinetic (PK) blood draws as informed consent was often given after the blood draws were to have been completed. As a result there were no patients with evaluable PK data. | Posted | 24 hours |
|
|
| 0 |
| 7 |
| 2 |
| 7 |
| 0 |
| 7 |
|
| Methaemoglobinaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Non-systematic Assessment |
|
Not provided
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Diastolic BP |
|