Anemia, Sickle CellPhase 1NCT01356485
Safety Study of MP4CO in Adult Sickle Cell Patients
A Phase 1 study testing MP4CO and Sodium chloride solution in people with Anemia, Sickle Cell and Sickle Cell Anemia, run by Sangart at 5 sites in 4 countries.
Trial summary
Sickle Cell Anemia is caused by an inherited hemoglobin disorder. Healthy red blood cells are discoid and can deform and move through small blood vessels to carry oxygen to all parts of the body. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anemia, Sickle Cell, Sickle Cell Anemia, Sickle Cell Disease
- What is being tested?
- MP4CO and Sodium chloride solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 5 sitesin 4 countries
- Study dates
- Jan 2012to Dec 2012
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult male or female patients (18 years of age or older) with diagnosed sickle cell disease based on Hb SS, or S/β0 Thalassemia genotype, who are clinically stable and not experiencing an acute episode of pain
Who cannot join
- At least 4 painful VOCs within the preceding year requiring hospital treatment
- Urgent care facility, hospital treatment or admission for treatment of a painful VOC within the previous 2 months
- History of a painful VOC lasting longer than 2 weeks or > 12 pain episodes requiring intervention in a medical facility (emergency room, urgent care or clinic) in preceding year
- Baseline VAS pain score ≥ 4 cm
- Hemoglobin < 6 g/dL
- Transfusion of packed red blood cells within previous 4 weeks
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- Currently on iron chelation therapy
- History of sickle cell disease-attributed CNS disease (including a) recent or past history of stroke; b) ongoing treatment with chronic transfusion therapy to prevent stroke; c. history of seizures or epilepsy; and d. evidence of or known overt cerebral vasculopathy or known cerebral vessel narrowing
- Evidence of pulmonary hypertension, based on an estimated systolic pulmonary artery pressure > 25 mmHg calculated from TRJ velocity from a transthoracic echocardiography (TTE) assessment at Screening visit or from a previous TTE assessment if it was done within 1 year prior to randomization
- Baseline oxygen saturation by pulse oximetry ≤ 90%
- History of a priapism within the last year
- History of hypertension requiring anti-hypertensive therapy
- Baseline bradycardia (heart rate < 60/min)
- History of myocardial infarction, myocardial ischemia, or angina
- Renal dysfunction or creatinine level within past 6 weeks of ≥ 1.2 mg/dL (≥ 106 µmol/L) or a urine protein/creatinine ratio (PCR) > 50 mg/mmol
- Hepatic dysfunction (AST or GGT > 3x ULN, or ALT >2x ULN, or conjugated bilirubin > 2x patient's baseline within the last 6 weeks)
- Positive pregnancy test
- Any acute or chronic condition which would limit the patient's ability to complete the study
- Evidence of, or known to be chronically abusing illegal drugs or excessive quantities of alcohol
- Known to have HIV, or active Hepatitis B or C infection, or tuberculosis
- Received any other investigational drug(s) within 30 days prior to randomization
- Professional or ancillary personnel involved with this study or in the employment of the investigator
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
United Kingdom2 sites
Guy's Hospital
London
King's College London
London
About this study
Official title: A Multi-center, Randomized, Double Blind, Dose Escalation Safety Study of MP4CO in Clinically Stable Adult Sickle Cell Patients
Sickle Cell Anemia is caused by an inherited hemoglobin disorder. Healthy red blood cells are discoid and can deform and move through small blood vessels to carry oxygen to all parts of the body. In sickle cell disease, as red blood cells circulate and oxygen is released in the circulatory system, the deoxygenated abnormal hemoglobin S can begin to polymerize. When this occurs, the red blood cells can become sticky and elongated. These sickled red blood cells are less flexible and will obstruct small blood vessels and block normal red blood cells from traveling through the circulatory system, which limits oxygen delivery to tissues and organs. This is known as a "sickle crisis".
Patients suffering from a sickle crisis experience severe pain and are at risk of stroke, heart attack or even death. By lowering the level of oxygen pressure at which sickling occurs and opening the vasculature and rapidly delivering oxygen directly to ischemic tissues, the addition of MP4CO to existing treatment protocols may alleviate pain associated with a sickle cell crisis, abort a crisis and/or potentially reduce the duration of a crisis. This could mean less time in the hospital and an improved quality of life for patients with sickle cell anemia.
Read the detailed description
To date, no specific agent has been approved to treat sickle cell crisis, to reduce the severity of a sickling crisis, or to shorten the duration of admission. Current therapy for a sickling crisis is limited to hydration and symptomatic pain relief with opiates when pain is severe enough to cause admission to hospital. Administration of oxygen by inhalation alone has not proven effective. Carbon monoxide (CO) binds to Hb S and, while attached, prevents and reverses polymerization of Hb S chains and consequent distortion of the red blood cell. Carbon monoxide at very low doses also acts as a messenger to cells, reducing inflammation, reducing oxygen requirements, and preventing programmed cell death (apoptosis).
The MP4 molecule can be modified to carry CO and other gases to enhance therapeutic benefit for certain patients. MP4CO is therefore designed to deliver therapeutic, non-toxic levels of CO, to provide an immediate metabolic signal to cells and to reduce inflammation. Once the CO is released from the compound, the MP4 molecule gets oxygenated in the lung and then delivers oxygen to ischemic tissues.
Previously published studies provide a good foundation to postulate that a chemically modified hemoglobin such as MP4CO might have the ideal properties as an oxygen therapeutic agent for treatment or reversal of a sickling crisis. The initial release of CO from MP4CO is predicted to have a therapeutic effect including immediate stabilization of Hb S to prevent further polymerization and reverse existing sickling, vasodilation of capillaries, and anti-inflammatory properties. The subsequent circulation of the MP4 molecule as an oxygen therapeutic agent (after converting to MP4OX following oxygenation in the lungs) will help to 1) preferentially oxygenate ischemic cells, 2) reverse partially sickled red cells, and 3) improve oxygenation of local tissues, thereby potentially ameliorating the painful VOC caused by red blood cell sickling. In addition, MP4CO has enhanced chemical stability, which enables storage at room temperature while minimizing methemoglobin formation.
- Conditions
- Anemia, Sickle Cell, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, Hemoglobin SC Disease, Sickle Cell Hemoglobin C Disease
- Being tested
- MP4CO, Sodium chloride solution
- Keywords
- Sickle cell anemia, Sickle cell disease, Sickling crisis, Vaso-occlusive crisis, Carboxyhemoglobin, Oxygen therapeutic, Hemoglobin solutions, Pegylated hemoglobin
- Medical subject headings
- Anemia, Sickle Cell, Hemoglobin SC Disease, Vaso-Occlusive Crises
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MP4CODrug
Also called Pegylated carboxyhemoglobin, PEG carboxyhemoglobin
43 mg/mL pegylated carboxyhemoglobin [≥ 90% CO hemoglobin saturation] in physiological acetate electrolyte solution
Sodium chloride solutionDrug
Also called Normal saline, Sodium chloride, 0.9% NaCL solution
Normal saline (0.9% sodium chloride solution)
| Study group | Role | What they receive |
|---|---|---|
| MP4CO | Experimental | Escalating doses of MP4CO, administered intravenously Receives: Drug: MP4CO |
| Saline | Placebo comparator | Normal saline (0.9% sodium chloride solution) Receives: Drug: Sodium chloride solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
No efficacy evaluations will be made in this safety study
Measured: 28 days
Secondary outcomes (5)
Adverse events
Measured: From 0 hrs after dosing through 28 Day Follow-up visit
Vital signs
Blood pressure, heart rate, respiration, temperature
Measured: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days
Laboratory assessments
Hematology, serum chemistry, urinalysis, renal function and biomarkers
Measured: Baseline, 24, 48, and 72 hours, and at 7 days
Pain levels
Patient self-assessment of pain levels using Visual Analogue Scale
Measured: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days
Pulmonary artery pressure assessment
Trans-thoracic Echocardiography (TTE)
Measured: Baseline, Pre-infusion, 1 hour post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2011 (estimated)
- Study startJan 2012
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anemia, Sickle CellStudies 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sangart
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Tania Small, MD, Study director, Sangart, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01356485
- Sponsor's protocol ID
- SCD-105
- Status last verified
- Aug 2013
- First submitted
- 17 May 2011
- Last updated
- 19 Aug 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Double Blind, Dose Escalation Safety Study of MP4CO in Clinically Stable Adult Sickle Cell Patients
- ClinicalTrials.gov ID
- NCT01356485
- Acronym / sponsor ID
- SCD-105
- Conditions
- Anemia, Sickle Cell, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorders, Hemoglobin SC Disease, Sickle Cell Hemoglobin C Disease
- Keywords
- Sickle cell anemia, Sickle cell disease, Sickling crisis, Vaso-occlusive crisis, Carboxyhemoglobin, Oxygen therapeutic, Hemoglobin solutions, Pegylated hemoglobin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- SangartIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 19 May 2011 (estimated)
- 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.
Sickle Cell Anemia is caused by an inherited hemoglobin disorder. Healthy red blood cells are discoid and can deform and move through small blood vessels to carry oxygen to all parts of the body. In sickle cell disease, as red blood cells circulate and oxygen is released in the circulatory system, the deoxygenated abnormal hemoglobin S can begin to polymerize. When this occurs, the red blood cells can become sticky and elongated. These sickled red blood cells are less flexible and will obstruct small blood vessels and block normal red blood cells from traveling through the circulatory system, which limits oxygen delivery to tissues and organs. This is known as a "sickle crisis".
Patients suffering from a sickle crisis experience severe pain and are at risk of stroke, heart attack or even death. By lowering the level of oxygen pressure at which sickling occurs and opening the vasculature and rapidly delivering oxygen directly to ischemic tissues, the addition of MP4CO to existing treatment protocols may alleviate pain associated with a sickle cell crisis, abort a crisis and/or potentially reduce the duration of a crisis. This could mean less time in the hospital and an improved quality of life for patients with sickle cell anemia.
Detailed description
To date, no specific agent has been approved to treat sickle cell crisis, to reduce the severity of a sickling crisis, or to shorten the duration of admission. Current therapy for a sickling crisis is limited to hydration and symptomatic pain relief with opiates when pain is severe enough to cause admission to hospital. Administration of oxygen by inhalation alone has not proven effective. Carbon monoxide (CO) binds to Hb S and, while attached, prevents and reverses polymerization of Hb S chains and consequent distortion of the red blood cell. Carbon monoxide at very low doses also acts as a messenger to cells, reducing inflammation, reducing oxygen requirements, and preventing programmed cell death (apoptosis).
The MP4 molecule can be modified to carry CO and other gases to enhance therapeutic benefit for certain patients. MP4CO is therefore designed to deliver therapeutic, non-toxic levels of CO, to provide an immediate metabolic signal to cells and to reduce inflammation. Once the CO is released from the compound, the MP4 molecule gets oxygenated in the lung and then delivers oxygen to ischemic tissues.
Previously published studies provide a good foundation to postulate that a chemically modified hemoglobin such as MP4CO might have the ideal properties as an oxygen therapeutic agent for treatment or reversal of a sickling crisis. The initial release of CO from MP4CO is predicted to have a therapeutic effect including immediate stabilization of Hb S to prevent further polymerization and reverse existing sickling, vasodilation of capillaries, and anti-inflammatory properties. The subsequent circulation of the MP4 molecule as an oxygen therapeutic agent (after converting to MP4OX following oxygenation in the lungs) will help to 1) preferentially oxygenate ischemic cells, 2) reverse partially sickled red cells, and 3) improve oxygenation of local tissues, thereby potentially ameliorating the painful VOC caused by red blood cell sickling. In addition, MP4CO has enhanced chemical stability, which enables storage at room temperature while minimizing methemoglobin formation.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MP4CO | Experimental | Drug: MP4COEscalating doses of MP4CO, administered intravenously |
| Saline | Placebo comparator | Drug: Sodium chloride solutionNormal saline (0.9% sodium chloride solution) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult male or female patients (18 years of age or older) with diagnosed sickle cell disease based on Hb SS, or S/β0 Thalassemia genotype, who are clinically stable and not experiencing an acute episode of pain
Key exclusion criteria (22 listed)
- At least 4 painful VOCs within the preceding year requiring hospital treatment
- Urgent care facility, hospital treatment or admission for treatment of a painful VOC within the previous 2 months
- History of a painful VOC lasting longer than 2 weeks or > 12 pain episodes requiring intervention in a medical facility (emergency room, urgent care or clinic) in preceding year
- Baseline VAS pain score ≥ 4 cm
- Hemoglobin < 6 g/dL
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 |
|---|---|---|
| MP4COAlso: Pegylated carboxyhemoglobin, PEG carboxyhemoglobin43 mg/mL pegylated carboxyhemoglobin [≥ 90% CO hemoglobin saturation] in physiological acetate electrolyte solution | Drug | MP4CO |
| Sodium chloride solutionAlso: Normal saline, Sodium chloride, 0.9% NaCL solutionNormal saline (0.9% sodium chloride solution) | Drug | Saline |
Primary outcome
No efficacy evaluations will be made in this safety study
Time frame: 28 days
5 secondary outcomes
Adverse events
Time frame: From 0 hrs after dosing through 28 Day Follow-up visit
Vital signs
Time frame: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days
Laboratory assessments
Time frame: Baseline, 24, 48, and 72 hours, and at 7 days
Pain levels
Time frame: Baseline, Hourly from 0 - 8 hours, 24, 48, and 72 hours, and at 7 days
Pulmonary artery pressure assessment
Time frame: Baseline, Pre-infusion, 1 hour post-infusion
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 19 Aug 2013.
- Sangart, Inc. (Home page)Link provided by the sponsor.
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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.
Tania Small, MD study director
Sangart, Inc.
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MP4CO and Sodium chloride solution in people with Anemia, Sickle Cell and Sickle Cell Anemia, run by Sangart at 5 sites in 4 countries.
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 1 inclusion and 22 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 19 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United Kingdom, France, Jamaica, Lebanon. 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?
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?
No efficacy evaluations will be made in this safety study (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Aug 2013.