Sickle Cell Disease Clinical Trial
Official title:
A Phase 2a, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, and Efficacy of 6R-BH4 in Subjects With Sickle Cell Disease
NCT number | NCT00445978 |
Other study ID # | SCD-001 |
Secondary ID | |
Status | Completed |
Phase | Phase 2 |
First received | |
Last updated | |
Start date | May 2007 |
Est. completion date | June 2009 |
Verified date | February 2021 |
Source | BioMarin Pharmaceutical |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
This Phase 2a, multicenter, open-label, dose-escalation study is designed to assess the safety and biologic activity of daily oral administration of 4 escalating doses of sapropterin dihydrochloride over 16 weeks in subjects with sickle cell disease. During an optional extension phase, the study will assess the safety, tolerability, and efficacy of extended treatment with sapropterin dihydrochloride, for a total of up to 2 years; The extension phase of this study was terminated.
Status | Completed |
Enrollment | 32 |
Est. completion date | June 2009 |
Est. primary completion date | August 2008 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 15 Years and older |
Eligibility | Inclusion Criteria: - Diagnosis of SCD, as confirmed by hemoglobin electrophoresis. - At least 15 years of age. - Dosage of medication(s) used to treat cardiac disease, hypertension (eg, calcium-channel blockers), elevated cholesterol, iron overload (eg, desferoxamine) and type 2 diabetes must be unchanged for at least 30 days prior to Screening. - Willing and able to provide written, signed informed consent, or in the case of subjects under the age of 18 years, provide written assent (if required) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures. - Willing and able to comply with all study procedures. - Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study. - Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been menopausal for at least 2 years, or had a tubal ligation at least 1 year prior to Screening, or who have had a total hysterectomy. Exclusion Criteria: - Requires chronic hypertransfusion therapy. - Sickle cell crisis during the 30 days prior to Screening. - Myocardial infarction, cerebral vascular accident, or pulmonary embolism during the 6 months prior to Screening. - History of bone marrow or hematopoietic stem cell transplantation. - Hepatic dysfunction (alanine aminotransferase [ALT][SGPT] > 2 times the upper limit of normal [ULN]). - Renal dysfunction with serum creatinine > 1.5 mg/dL. - On outpatient oxygen therapy, or continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP) therapy. - Uncontrolled hypertension (defined as blood pressure > 135/85 mm Hg) at Screening. - History of chronic symptomatic hypotension. - Concurrent disease or condition that would interfere with study participation or safety, including, but not limited to: bleeding disorders, history of syncope or vertigo, severe gastroesophageal reflux disease (GERD), arrhythmia, organ transplant, organ failure, type 1 diabetes mellitus (subjects with type 2 diabetes are allowed), or serious neurological disorders (including seizures). - Hydroxyurea therapy during the 3 months prior to Screening or anticipated need for hydroxyurea during the course of the study. - Treatment with any phosphodiesterase (PDE) 5 inhibitor (Viagra®, Cialis®, Levitra® or Revatio™), any PDE 3 inhibitor (eg, cilostazol, milrinone, or vesnarinone), pentoxifylline (Trental®), nitrate/nitrite-based vasodilators, bosentan (Tracleer®), L-arginine, levodopa, or dietary supplements containing L-arginine or gingko biloba within 30 days prior to Screening, or anticipated need for treatment with any of these agents during the course of the study. - Requirement for concomitant treatment with any drug known to inhibit folate metabolism (eg, methotrexate). - Previous treatment with vascular endothelial growth factor (VEGF) or VEGF inhibitors. - Has known hypersensitivity to sapropterin dihydrochloride or its excipients. - Use of any investigational product, device, or any formulation of BH4 within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments. - Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study. - Any condition that, in the view of the Investigator, places the subject at high risk of poor treatment compliance or of not completing the study. |
Country | Name | City | State |
---|---|---|---|
n/a |
Lead Sponsor | Collaborator |
---|---|
BioMarin Pharmaceutical |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | A treatment-emergent adverse events (TEAE) is any adverse events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration. | Up to 16 weeks | |
Secondary | Change From Baseline in the Peripheral Arterial Tonometry (PAT) Scores | The PAT score was calculated using the ratio between the arterial pulse wave amplitude following a 5-minute arterial occlusion in the forearm to the pre-occlusion value (Reactive Hyperemia Index). A value of | At Baseline, Week 4, 8, 12 and 16. | |
Secondary | Change From Baseline in the Urine 8-Isoprostane | Change in urine 8-isoprostane from Baseline to post-treatment visit is calculated by subtracting the Baseline measurement from the post-treatment measurement. This outcome was used to assess change in oxidative stress. | At Baseline, Week 4, 8, 12 and 16. | |
Secondary | Change From Baseline in the Urine Spot Albumin to Creatinine Ratio | Change in Urine Albumin to Creatinine Ratio from Baseline to post-treatment visit is calculated by subtracting the Baseline measurement from the post-treatment measurement. This outcome was used to assess change in renal function. | At Baseline, Week 4, 8, 12 and 16. | |
Secondary | Change From Baseline in the Tricuspid Regurgitant Velocity (TRV) | Change in tricuspid regurgitant velocity (TRV) from Baseline to post-treatment visit is calculated by subtracting the Baseline measurement from the post-treatment measurement. | At Baseline, Week 4, 8, 12 and 16. |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02227472 -
Working Memory and School Readiness in Preschool-Aged Children With Sickle Cell Disease
|
||
Recruiting |
NCT06301893 -
Uganda Sickle Surveillance Study (US-3)
|
||
Recruiting |
NCT04398628 -
ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
|
||
Completed |
NCT02522104 -
Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
|
Phase 4 | |
Recruiting |
NCT04688411 -
An mHealth Strategy to Improve Medication Adherence in Adolescents With Sickle Cell Disease
|
N/A | |
Terminated |
NCT03615924 -
Effect of Ticagrelor vs. Placebo in the Reduction of Vaso-occlusive Crises in Pediatric Patients With Sickle Cell Disease
|
Phase 3 | |
Not yet recruiting |
NCT06300723 -
Clinical Study of BRL-101 in Severe SCD
|
N/A | |
Recruiting |
NCT03937817 -
Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
|
||
Completed |
NCT04134299 -
To Assess Safety, Tolerability and Physiological Effects on Structure and Function of AXA4010 in Subjects With Sickle Cell Disease
|
N/A | |
Completed |
NCT04917783 -
Health Literacy - Neurocognitive Screening in Pediatric SCD
|
N/A | |
Completed |
NCT02580565 -
Prevalence of Problematic Use of Equimolar Mixture of Oxygen and Nitrous Oxide and Analgesics in the Sickle-cell Disease
|
||
Recruiting |
NCT04754711 -
Interest of Nutritional Care of Children With Sickle Cell Disease on Bone Mineral Density and Body Composition
|
N/A | |
Completed |
NCT04388241 -
Preliminary Feasibility and Efficacy of Behavioral Intervention to Reduce Pain-Related Disability in Pediatric SCD
|
N/A | |
Recruiting |
NCT05431088 -
A Phase 2/3 Study in Adult and Pediatric Participants With SCD
|
Phase 2/Phase 3 | |
Completed |
NCT01158794 -
Genes Influencing Iron Overload State
|
||
Recruiting |
NCT03027258 -
Point-of-Delivery Prenatal Test Results Through mHealth to Improve Birth Outcome
|
N/A | |
Withdrawn |
NCT02960503 -
Macrolide Therapy to Improve Forced Expiratory Volume in 1 Second in Adults With Sickle Cell Disease
|
Phase 1/Phase 2 | |
Completed |
NCT02567682 -
Drug Interaction Study of GBT440 With Caffeine, S-warfarin, Omeprazole, and Midazolam in Healthy Subjects
|
Phase 1 | |
Completed |
NCT02567695 -
A Single-Dose Relative Bioavailability Study Of GBT440 300 mg Capsules in Healthy Subjects
|
Phase 1 | |
Withdrawn |
NCT02630394 -
A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
|
Phase 1 |