A Study to Evaluate MP4CO for the Acute Treatment of Vaso-occlusive Crises in Subjects with Sickle Cell Disease

• Register: EUCTR
• Last refreshed on: 21 August 2017
• Main ID: EUCTR2013-001600-11-BE
• Date of registration: 02/09/2013
• Prospective Registration: Yes
• Primary sponsor: Sangart, Inc.
• Public title: A Study to Evaluate MP4CO for the Acute Treatment of Vaso-occlusive Crises in Subjects with Sickle Cell Disease
• Scientific title: A Phase 2 Multi-center, Randomized, Double-blind, Comparator-Controlled Dose Finding Study to Evaluate MP4CO for the Acute Treatment of Vaso-occlusive Crises in Subjects with Sickle Cell Disease
• Date of first enrolment: 24/10/2013
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001600-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: yes Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bahrain, Belgium, Brazil, France, Lebanon, Netherlands, Oman, Qatar, Saudi Arabia, Turkey, United Kingdom

Contacts

• Name: Regulatory Affairs
• Affiliation: Sangart Inc.

• Name: Regulatory Affairs
• Affiliation: Sangart Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Enrollment Eligibility - Inclusion Criteria
•Signed Informed Consent (and assent as required for minors)
•Diagnosis of SCD (known HbSS or HbSß0)
•Sixteen years of age or older
•Prior history of at least one VOC requiring hospitalization within the last 24 months

Randomization Eligibility - Inclusion Criteria
•Subject has consented for participation in the MP4CO-13-SCD-206 trial
• Diagnosis of an uncomplicated VOC consisting of all of the following:
- Pain or tenderness affecting at least one part of the body
- VAS pain level = 6 cm at any point in time from start of VOC to randomization
- Requires parenteral analgesia (including intravenous or subcutaneous routes)
- Pain from VOC is the primary symptom at presentation
•Requires admission to the hospital for VOC management
•Pain is primarily due to VOC and not attributed to any other cause
•Able to receive first dose of study drug within 12 hours of admission to the hospital for VOC management

If a patient, not enrolled in the trial, presents with a VOC they may be enrolled into the trial at the time of VOC admission and proceed immediately to randomization if they meet all Enrollment Criteria and complete the Baseline Assessments prior to randomization.
Are the trial subjects under 18? yes
Number of subjects for this age range: 200
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Enrollment Eligibility - Exclusion Criteria
•= 5 VOCs within the preceding 6 months requiring Emergency Room (ER) visits or hospital admissions
•History of overt stroke or cerebral vascular accident within the previous 12 months
•Remained in the hospital for =2 weeks (14 days) for VOC management within the previous 6 months
•Known pulmonary hypertension based on an estimated tricuspid regurgitant jet velocity (TRJV) >2.90 m/s or definitive diagnosis by prior right heart catheterization
•Baseline SaO2 level by pulse oximetry <92% on room air
•Systemic hypertension (baseline systolic pressure = 160 or diastolic pressure = 90)
•History of myocardial infarction, myocardial ischemia, or angina
•On a chronic red blood cell transfusion therapy program (simple or exchange)
•Renal dysfunction presenting with a GFR<60 mL/min/1.73m
•Any diagnosis of a concurrent chronic debilitating disease that may affect the completion of the study or results of the study as determined by the investigator
•Currently enrolled in any other investigational treatment study
•Significant substance abuse.
•Known to have HIV, active hepatitis B, or C infection, or active tuberculosis

Randomization Eligibility - Exclusion Criteria:
•Suspected diagnosis of Acute Chest Syndrome (ACS) as evidenced by one or more of the following at presentation to the medical facility:
a.Fever >38.5°C with new hypoxia on pulse oximetry
b.Chest radiographic findings of a new infiltrate
c.Suspicious clinical exam for ACS (including but not limited to increased work of breathing, dyspnea, wheezing, hypoxia or rales)
•Diagnosed or suspected systemic infection as evidenced by one or more of the following at presentation to the medical facility:
a.Fever =39°C
b.Fever >38.5°C accompanied by corrected White Blood Cell (WBC) count of = 30 × 109/L or less than 2 × 109/L
c.Positive findings suspicious for infections based on physical exam or/and diagnostic tests including but not limited to radiographic tests, laboratory tests, cerebral spinal fluid evaluation
d.Complicated urinary tract infection (infection eg. involving the upper urinary tract i.e. pyelonephritis or with systemic symptomatology)
•Hemoglobin level <5 g/dL (<50 g/L) at time of randomization
•Priapism ongoing for >2 hours prior to randomization
•Transient ischemic attack or seizure within the last 60 days
•Admission for VOC within the last 60 days
•Admission for ACS, significant bleeding, splenic sequestration, hepatic sequestration within the last 30 days.
•=5 VOCs requiring Emergency Room visits or hospital admissions within the preceding 6 months
•Exchange red blood cell transfusion or simple packed red blood cell transfusion within the previous 30 days
•SaO2 level by pulse oximetry <92% on room air
•Hypertension (systolic pressure =160 mmHg or diastolic pressure =90) (within 1 hour prior to randomization)
•Bradycardia (HR <60beats/min) (within 1 hour prior to randomization)
•Renal dysfunction defined by a GFR <60 ml/min/1.73m2
•Hepatic dysfunction (AST or GGT >3X ULN, or ALT >2XULN)
•Pregnant or breastfeeding



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Sickle cell disease (SCD) is an autosomal recessive disorder of the ß globin gene of the hemoglobin molecule. One single point mutation results in a lifetime of chronic morbidity and mortality. Vaso-occlusive crises (VOCs), also known as pain crises, remain the hallmark of this disease and are the leading cause of hospitalization in SCD.

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: MP4CO
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: N/A
Current Sponsor code: MP4CO
Other descriptive name: MP4CO
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 43-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: 1. To determine the most effective dose of MP4CO at reducing the time to VOC resolution (and thereby decreasing the duration of hospitalization) in subjects with Sickle Cell Disease (SCD) admitted for vaso-occlusive crisis (VOC) management.

2. To evaluate the safety and tolerability of MP4CO treatment administered during a VOC in subjects with SCD.

Primary end point(s): The primary endpoint of this study is time to VOC resolution (TTVOCR) as assessed by the investigator. It is defined as the time from randomization to VOC resolution which is determined by achieving 2 out 3 of the following:
• Cessation of intravenous and or subcutaneous opioid analgesia
• Recovery of ambulation by at least 20% unless the subject was unable to ambulate for reasons other than a VOC crisis
• Ready for discharge as defined by treating physician and subject

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Ongoing

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints are as follows:
• Proportion of subjects with a reduction in VAS pain levels by 2 cm maintained = 4 hours compared to worst score on day of admission.
• Proportion of subjects with at least one return visit to ER within 7 days of discharge.
• Proportion of subjects with at least one re-admission to hospital for treatment of VOC within 7 days of discharge.
• Proportion of subjects with ACS complications during hospitalization for treated VOC.

Safety endpoints will include the following:
• Incidence of AEs and SAEs
• Physical examination findings
• Vital sign measurements
• Urinalysis parameters
• Hematology parameters
• Blood chemistry parameters

Timepoint(s) of evaluation of this end point: Ongoing

Secondary ID(s)

NCT01925001

2013-001600-11-GB

MP4CO-13-SCD-206

Source(s) of Monetary Support

Sangart, Inc.