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| ID | Type | Description | Link |
|---|---|---|---|
| 2017-004568-37 | EudraCT Number |
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An open label, safety and pharmacokinetic study of oral hydroxyurea solution administered to children from 6 months to 17.99 years (i.e. to the day before 18th birthday), with a 12 to 15 month treatment period for each participant. The study treatment duration will be for 6 months at the maximum tolerated dose [MTD], which is usually reached by 6 months after initiation of treatment. For patients in whom time to MTD is longer than 6 months or not achieved at all, the maximum duration of study treatment will be 15 months.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open Label | Experimental | Novel oral solution formulation of hydroxyurea |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oral Hydroxyurea (100 mg/mL) Solution | Drug | Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day. |
| Measure | Description | Time Frame |
|---|---|---|
| Clearance (CL/F) | Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug). | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
| Volume of Distribution (V/F) | Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug). | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
| Time to Maximum Concentration (Tmax) | Mean Tmax (h) pharmacokinetic parameter derived using the final population PK model. | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
| Maximum Plasma Concentration Cmax (ug/mL) | Mean Cmax (ug/mL) pharmacokinetic parameter derived using the final population PK model. | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
| Area Under Plasma Concentration Time Curve (AUC 0-Inf) | Mean AUC 0-Infinity (hr*ug/mL) pharmacokinetic parameters derived using the final population PK model. | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
| Terminal Half-life (Hours) | Mean Terminal Half-life (hours) pharmacokinetic parameter derived using the final population PK model. | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Incidence of Adverse events during the course of the trial from screening to final follow up phone call at Week 64. Relatedness refers to 'at least possibly related to the IMP', with severity/toxicity assessed using the CTCAE Toxicity Grade and seriousness based on the standard definition for SAE in accordance with GCP. With the exception of SCA related events, requiring >7day hospitalisation, or extension of hospitalisation before being reported as an SAE due to their frequency within the disease population. All other non-SCA related SAEs were reportable. |
| Measure | Description | Time Frame |
|---|---|---|
| Transcranial Doppler Velocity | Exploratory Endpoint; clinical output of hydroxyurea treatment | Baseline to Week 40-56 (Follow up scan). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Angela E Rankine- Mullings, MD | University of the West Indies, Mona, Kingston, Jamaica | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dr Angela E Rankine- Mullings | Kingston | Jamaica | ||||
| Birmingham Women's and Children's NHS Foundation Trust |
33 participants enrolled met the inclusion criteria; 32 initiated treatment with open label Hydroxyurea and one participant discontinued pre-treatment.
Participants were recruited from one Jamaican sickle cell clinic (n=12) and five UK hospitals (n=20). The first participant was enrolled on 03 Jan 2019 and the last participant was enrolled on 16 Dec 2020.
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| ID | Title | Description |
|---|---|---|
| FG000 | Oral Hydroxyurea | Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day. Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 3, 2021 | Dec 14, 2022 |
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Open label, observational, pharmacokinetic study of oral hydroxyurea solution administered to children from 6 months-17.99 years over a 12-15-month period
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| Screening Up to Week 64 |
| Absolute Neutrophil Count (ANC) | Safety review for haematological toxicity (mild myelosuppression target: 1-3x10^9/L) | Baseline and Week 60 (or final visit); max 15 months on treatment |
| White Blood Cell Count (Leukocytes) | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Baseline to Week 60 or Final Visit; max 15 months on treatment |
| Platelets | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Baseline to Week 60 (or Final Visit), max 15 months on treatment |
| Mean Corpuscular Hemoglobin (MCH) | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Baseline to Week 60 (or Final Visit), max 15 months on treatment |
| Hematocrit | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Up to Week 60 |
| Bilirubin | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Up to Week 60 |
| Elevation in Liver Function Tests (LFTs) | Impact of Hydroxyurea on Safety, Hematology and Biochemistry, including Liver Function Tests (LFTs): Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) | Up to Week 60 |
| Hemoglobin | Safety and efficacy of hydroxyurea therapy | Baseline to Week 60 (or Final Visit); max 15 months on treatment |
| Bacterial Infections | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Up to Week 60 |
| Viral Infections | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Up to Week 60 |
| Fungal Infections | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Up to Week 60 |
| Leg Ulcers | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Up to Week 60 |
| Fetal Hemoglobin | Biomarker endpoints of Hydroxyurea efficacy | Baseline to Week 60 (or Final Visit); max 15 months on treatment |
| Mean Corpuscular Volume (MCV) | Biomarker endpoints of Hydroxyurea efficacy | Baseline to Week 60 (or Final Visit); max 15 months on treatment |
| Cystatin C | Biomarker Endpoints | PK1 (day 1), week 20-32 (6 months) and Week 60 (Final Visit) |
| Incidence of Acute Vaso-Occlusive Pain Crises (VOC) | Hospitalization Incidence for 12 Months Prior to and After First Dose of IMP (Safety Population) for vaso-occlusive crisis (Mean [SD]) | 12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMP |
| Number and Frequency of Blood Transfusions | Clinical status endpoints, related to blood transfusions for treatment of SCA, this may be hospitalization, A&E, or in-clinic treatment from safety population (n=32) | Up to Week 60 |
| Acute Chest Syndrome (ACS) | Hospitalization Incidence for 12 Months Prior to and After First Dose of IMP (Safety Population) for Acute Chest Syndrome (Mean [SD]) | 12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMP |
| Hospitalizations | Clinical Status endpoints, all hospitalisations (not ER/Accident without hospitalization) (Mean [SD]) | 12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMP |
| Dose Escalation i.e. Maximum Tolerated Dose (MTD) | Summary of maximum tolerated dose achieved in mg/kg (Mean [SD]) | Screening Up to Final Visit (Week 60 or Withdrawal), maximum 15 months on IMP |
| Other SCA-related Hospitalizations | Clinical parameters (symptoms), secondary clinical status endpoints (not including ACS, VOC, Other Non-SCA related) (mean [SD]) | 12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMP |
| Parent/Caregiver Palatability and Acceptability Questionnaire | Clinical status endpoints. Visual Analogue scale used to determine, taste, smell, aftertaste, acceptability and ease of dosing (1-100mm scale) with 1 being worst possible and 100 being best possible. Assessed for <6 years of age by parents/guardians. Assessed for >6 years of age, combination of parent/guardian and participant responses. | Taken once at any point after 8 weeks on study medication (or at early Withdrawal) |
| Vitamin D | Biochemistry | From Screening Up to Final Visit (Week 60 or WD) |
| Other Non-SCA-related Hospitalizations | Clinical parameters (symptoms), secondary clinical status endpoints (not including ACS, VOC, Other SCA-related) | 12 months prior to treatment and 12 months post-treatment; maximum 15 months on IMP |
| Birmingham |
| United Kingdom |
| Alder Hey Children's NHS Foundation Trust | Liverpool | United Kingdom |
| Evelina London Children's Hospital | London | United Kingdom |
| King's College Hospital NHS Foundation Trust | London | United Kingdom |
| The Royal London Children's Hospital, Barts Health NHS Trust | London | United Kingdom |
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| Pre-treatment Discontinuation |
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| Safety Population |
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| Age Group (6 Months - 1.99 Years) |
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| Discontinuations From Age Group (6 Months - 1.99 Years) |
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| Completed From Age Group (6 Months - 1.99 Years) |
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| Age Group (2 - 5.99 Years) |
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| Discontinuations From Age Group (2 - 5.99 Years) |
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| Completions From Age Group (2 - 5.99 Years) |
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| Age Group (6 - 17.99 Years) |
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| Discontinuations From Age Group (6 - 17.99 Years) |
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| Completions From Age Group (6 - 17.99 Years) |
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| COMPLETED | Overall from all age groups |
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| NOT COMPLETED |
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Participant demographics were summarized for all 33 participants. One participant discontinued prior to receiving a first dose of IMP. The remaining safety population consisted of 32 participants who all received at least one dose of the IMP and one valid primary efficacy PK measurement. This safety population was used for all analyses of baseline characteristics, secondary and exploratory outcomes, as well as safety outcomes.
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| ID | Title | Description |
|---|---|---|
| BG000 | Oral Hydroxyurea | Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day. Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Overall demographic population of 33 participants. | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Overall demographic population of 33 participants. | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Measure Analysis Population Description: Overall demographic population of 33 participants. This has been further subdivided to give the demographic per age group. All participants identified as Black or African American except for two UK participants who self-described as Other: "Caribbean" [sic] and "Black British". | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| SCA Type | Measure Analysis Population Description: SCD Genotype of overall demographic population of 33 participants. | SCD Genotype of overall demographic population of 33 participants. SCD is caused by a mutation in the β-globin gene HBB. Hemoglobin SS (HbSS) represents a large proportion of SCD in the Americas, UK, and certain regions of Africa while higher proportions of hemoglobin SC are observed in Burkina Faso and hemoglobin Sβ-thalassemia (HbS/β0 or HbS/β+) in Greece and India. Patients with HbSS and HbS/βo-thalassaemia typically have a more severe course of disease than other genotypes. | Count of Participants | Participants |
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| Height | Height in (cm) for safety population at baseline, defined as the last non-missing measurement prior to first exposure to oral hydroxurea. | Overall safety population of 32 participants, data available at screening for 31 participants. Height or length was unobtainable for 1 participant who was under the age of 2 years (Age group 6 months - 1.99 years). | Mean | Standard Deviation | cm |
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| Weight | Weight in (kg) for safety population at baseline, defined as the last non-missing measurement prior to first exposure to oral hydroxyurea. | Overall safety population of 32 participants. | Mean | Standard Deviation | kg |
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| 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 | Clearance (CL/F) | Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug). | Clearance value for patient of 15.05 kg | Posted | Mean | 95% Confidence Interval | L/hr | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
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| Primary | Volume of Distribution (V/F) | Model estimated Pharmacokinetic Parameter (PK population: n=32, having received at least one dose of study drug). | Volume of distribution for central and peripheral compartments for patient of 15.05 kg | Posted | Mean | 95% Confidence Interval | L | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
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| Primary | Time to Maximum Concentration (Tmax) | Mean Tmax (h) pharmacokinetic parameter derived using the final population PK model. | PK population = 32 participants, who have received at least one dose at 15 mg/kg and have at least one sample of PK plasma above the lower limit of quantification | Posted | Mean | Standard Deviation | hours | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
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| Primary | Maximum Plasma Concentration Cmax (ug/mL) | Mean Cmax (ug/mL) pharmacokinetic parameter derived using the final population PK model. | PK population: n=32 safety population, having received at least one dose of study drug at 15mg/kg and one sample of PK plasma above the lower limit of quantification. | Posted | Mean | Standard Deviation | ug/mL | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
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| Primary | Area Under Plasma Concentration Time Curve (AUC 0-Inf) | Mean AUC 0-Infinity (hr*ug/mL) pharmacokinetic parameters derived using the final population PK model. | PK population = 32 participants receiving at least one dose of 15mg/kg hydroxyurea and have at least one PK plasma sample above lower limit of quantification. | Posted | Mean | Standard Deviation | hr*ug/mL | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
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| Primary | Terminal Half-life (Hours) | Mean Terminal Half-life (hours) pharmacokinetic parameter derived using the final population PK model. | PK Population n=32 where all subjects received at least one dose of 15 mg/kg hydroxyurea and have at least one sample of PK plasma above the lower limit of quantification. | Posted | Mean | Standard Deviation | hours | 0, 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, and 12 hours post-dose on Day 1 and Day 2 (Week 20-36) |
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| Secondary | Adverse Events | Incidence of Adverse events during the course of the trial from screening to final follow up phone call at Week 64. Relatedness refers to 'at least possibly related to the IMP', with severity/toxicity assessed using the CTCAE Toxicity Grade and seriousness based on the standard definition for SAE in accordance with GCP. With the exception of SCA related events, requiring >7day hospitalisation, or extension of hospitalisation before being reported as an SAE due to their frequency within the disease population. All other non-SCA related SAEs were reportable. | Safety population n=32. Overall 339 AEs in 31 participants recorded. 7 adverse events included in this list of 339 were defined as 'Serious' as per the protocol definition (i.e. SCA related and >7days hospitalisation). A separate SAE report was made at that time with a clearly defined start and end date to be able to denote a resolution to the 'seriousness' criteria as this is an ongoing chronic condition. | Posted | Number | events | Screening Up to Week 64 |
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| Secondary | Absolute Neutrophil Count (ANC) | Safety review for haematological toxicity (mild myelosuppression target: 1-3x10^9/L) | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | x10^9 neutrophils/L | Baseline and Week 60 (or final visit); max 15 months on treatment |
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| Secondary | White Blood Cell Count (Leukocytes) | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Leukocytes Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | 10^9 leukocytes/L | Baseline to Week 60 or Final Visit; max 15 months on treatment |
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| Secondary | Platelets | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | 10^9 platelets/L | Baseline to Week 60 (or Final Visit), max 15 months on treatment |
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| Secondary | Mean Corpuscular Hemoglobin (MCH) | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | pg | Baseline to Week 60 (or Final Visit), max 15 months on treatment |
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| Secondary | Hematocrit | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | % by volume of red blood cells in blood | Up to Week 60 |
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| Secondary | Bilirubin | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | umol/L | Up to Week 60 |
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| Secondary | Elevation in Liver Function Tests (LFTs) | Impact of Hydroxyurea on Safety, Hematology and Biochemistry, including Liver Function Tests (LFTs): Alkaline Phosphatase (ALP), Gamma Glutamyl Transferase (GGT), Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | ukat/L | Up to Week 60 |
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| Secondary | Hemoglobin | Safety and efficacy of hydroxyurea therapy | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | g/dL | Baseline to Week 60 (or Final Visit); max 15 months on treatment |
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| Secondary | Bacterial Infections | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment. | Posted | Number | events | Up to Week 60 |
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| Secondary | Viral Infections | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment. | Posted | Number | Events | Up to Week 60 |
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| Secondary | Fungal Infections | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment. | Posted | Number | events | Up to Week 60 |
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| Secondary | Leg Ulcers | Impact of Hydroxyurea on Safety, Hematology and Biochemistry | At screening, subjects' experiences of clinical SCA symptoms within the 12 months prior to the screening visit were recorded. At subsequent visits, subjects' experiences of SCA symptoms since the previous visit were recorded, until end of study. Each subject counted a maximum of once each per SCA symptom for before treatment and after treatment. | Posted | Number | events | Up to Week 60 |
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| Secondary | Fetal Hemoglobin | Biomarker endpoints of Hydroxyurea efficacy | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | Hemoglobin F/Total Hemoglobin % | Baseline to Week 60 (or Final Visit); max 15 months on treatment |
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| Secondary | Mean Corpuscular Volume (MCV) | Biomarker endpoints of Hydroxyurea efficacy | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | fL | Baseline to Week 60 (or Final Visit); max 15 months on treatment |
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| Secondary | Cystatin C | Biomarker Endpoints | Baseline value is the last non-missing assessment prior to first exposure of oral HU. Analysis was from initiation of study drug, again at ~6months (between 20-32 weeks) and at final study visit. Week 28 (6 months - 1.99 years) no measures were analysed at this timepoint. | Posted | Mean | Standard Deviation | nmol/L | PK1 (day 1), week 20-32 (6 months) and Week 60 (Final Visit) |
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| Secondary | Incidence of Acute Vaso-Occlusive Pain Crises (VOC) | Hospitalization Incidence for 12 Months Prior to and After First Dose of IMP (Safety Population) for vaso-occlusive crisis (Mean [SD]) | Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall. | Posted | Mean | Standard Deviation | hospitalisation events per month | 12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMP |
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| Secondary | Number and Frequency of Blood Transfusions | Clinical status endpoints, related to blood transfusions for treatment of SCA, this may be hospitalization, A&E, or in-clinic treatment from safety population (n=32) | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. Age group (6 months to 1.99 years) did not report any blood transfusions. | Posted | Number | events (number of transfusions) | Up to Week 60 |
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| Secondary | Acute Chest Syndrome (ACS) | Hospitalization Incidence for 12 Months Prior to and After First Dose of IMP (Safety Population) for Acute Chest Syndrome (Mean [SD]) | Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall. | Posted | Mean | Standard Deviation | hospitalisation events per month | 12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMP |
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| Secondary | Hospitalizations | Clinical Status endpoints, all hospitalisations (not ER/Accident without hospitalization) (Mean [SD]) | Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall. | Posted | Mean | Standard Deviation | hospitalisation events per month | 12 months prior to treatment and time-averaged 12 months post-treatment; maximum 15 months on IMP |
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| Secondary | Dose Escalation i.e. Maximum Tolerated Dose (MTD) | Summary of maximum tolerated dose achieved in mg/kg (Mean [SD]) | Clinical status endpoints; Safety population = 32 participants, who received at least one dose of IMP. Week 60 is the final study visit, or withdrawal point at which point IMP was halted. MTD only summarized for subjects who investigator denoted as achieving MTD during the study (n=20). If several doses were marked as MTD for the subject, the highest dose was used. | Posted | Mean | Standard Deviation | mg/kg | Screening Up to Final Visit (Week 60 or Withdrawal), maximum 15 months on IMP |
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| Secondary | Other SCA-related Hospitalizations | Clinical parameters (symptoms), secondary clinical status endpoints (not including ACS, VOC, Other Non-SCA related) (mean [SD]) | Time-averaged hospitalizations after treatment was determined by dividing incidence of hospitalizations prior to treatment by 12 if study end date was more than a year after treatment start date, or by dividing by (End date - Treatment Start Date)/30.4375 otherwise. Hospitalizations did not include visits to ER/accident without hospitalization. Hospitalizations were sub-categorized by a medical monitor. Data were obtained through medical record review and study participant recall. | Posted | Mean | Standard Deviation | hospitalisation events per month | 12 months prior to treatment and time averaged 12 months post-treatment; maximum 15 months on IMP |
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| Secondary | Parent/Caregiver Palatability and Acceptability Questionnaire | Clinical status endpoints. Visual Analogue scale used to determine, taste, smell, aftertaste, acceptability and ease of dosing (1-100mm scale) with 1 being worst possible and 100 being best possible. Assessed for <6 years of age by parents/guardians. Assessed for >6 years of age, combination of parent/guardian and participant responses. | Results are presented for all 32 safety participants. | Posted | Mean | Standard Deviation | mm | Taken once at any point after 8 weeks on study medication (or at early Withdrawal) |
|
| ||||||||||||||||||||||||||
| Secondary | Vitamin D | Biochemistry | Safety population = 32 participants, who received at least one dose of oral hydroxyurea. Baseline value is the last non-missing assessment prior to first exposure of oral hydroxyurea. Week 60 is the final study visit or withdrawal at which point oral hydroxyurea was halted. | Posted | Mean | Standard Deviation | nmol/L | From Screening Up to Final Visit (Week 60 or WD) |
|
| ||||||||||||||||||||||||||
| Secondary | Other Non-SCA-related Hospitalizations | Clinical parameters (symptoms), secondary clinical status endpoints (not including ACS, VOC, Other SCA-related) | Hospitalizations 'Prior to Treatment' having a start date within 1 year prior to initial treatment. Hospitalizations 'After Treatment' defined as all hospitalizations (not ER/Accident without hospitalization) within 1 year after treatment start date. | Posted | Mean | Standard Deviation | events | 12 months prior to treatment and 12 months post-treatment; maximum 15 months on IMP |
|
| ||||||||||||||||||||||||||
| Other Pre-specified | Transcranial Doppler Velocity | Exploratory Endpoint; clinical output of hydroxyurea treatment | Time Averaged Mean Maximum Velocity (TAMV) in cm/sec at Baseline and Week 40-56 Visit (Safety Population). max 15 months on treatment at Week 60. Only participants with non-missing values at screening and end of study are included in the Baseline shift summary (change from baseline). | Posted | Mean | Standard Deviation | cm/sec | Baseline to Week 40-56 (Follow up scan). |
|
|
Screening to safety follow up call at 64 weeks (maximum 15 months on treatment).
Protocol definition of SAE for SCA associated complications, AEs only became reportable SAEs if the hospital admission was prolonged >7days. SCA related hospitalisations <7days recorded as AEs due to the frequency of admissions within population and chronic nature of the condition. Attendance of emergency room without admission or for elective procedures were not considered SAEs unless prolonged. All SAEs unrelated to SCA condition were reportable in line with standard definitions.
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 | Oral Hydroxyurea | Participants received Oral Hydroxyurea 15 mg/kg once daily. Escalated by 5 mg/kg/day every 8-12 weeks until maximum tolerated dose achieved, up to a maximum 35 mg/kg/day. Hydroxyurea: Oral Hydroxyurea 100 mg/ml solution | 0 | 32 | 6 | 32 | 31 | 32 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute Chest Syndrome (ACS) Grade 3 | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Grade 3, requiring hospitalisation >7days (n=3 participants) |
|
| Acute Chest Syndrome (ACS) Grade 2 | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Grade 2, requiring hospitalisation >7days |
|
| Vaso-occlusive Crisis (VOC) | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | Grade 3, requiring hospitalisation >7days (n=2 participants) |
|
| Anemia secondary to SCD | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | Grade 3, requiring hospitalisation for oxygen therapy and blood transfusion |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Neutropenia/Low ANC Count | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | Haematological toxicity (ANC <1.0x10^9/L). n=3 Grade 3 events in n=3 participants; n=4 events in n=4 participants at least possibly related. In n=3 in the 6month-1.99 year age group, associated with viral/other illness or dose titration. |
|
| Thrombocytopenia/Low Platelet Count | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | Haematological toxicity (Platelet <80x10^9/L) were \ |
|
| Haemoglobin (Hb) Decreased | Investigations | MedDRA (23.1) | Systematic Assessment | Haematological toxicity (Hb <4.5g/dL or 20% drop). n=1 event Grade 3 in n=1 participant; n=2 events at least possibly related in n=1 participant in the 6month-1.99 year age group. |
|
| Absolute Reticulocyte Count (ARC) Decreased | Investigations | MedDRA (23.1) | Systematic Assessment | Haematological toxicity (ARC <80x10^9/L; unless Hb >9.0g/dL). All events \ |
|
| Red Blood Cell (RBC) Count Decreased | Investigations | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Gamma-Glutamyltransferase (GGT) Increased | Investigations | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Hematocrit (HCT) Decreased | Investigations | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Diarrhoea; n=1 event at least possibly related in n=1 participant; n=4 unrelated event of mild/moderate severity in n=3 participants. |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Nail Discolouration | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | Rash; n=1 at least possibly related event in n= 1 participant; n=2 unrelated events in n=2 participants of mild/moderate severity. |
|
| Rash Papular | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | *Related Treatment Emergent Adverse Event (TEAE) in Safety population (n=32). Where relatedness is defined as anything at least possibly related to the IMP. |
|
| Sickle Cell Anemia with Crisis/Vaso-Occlusive Crisis (VOC) | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | 'SCA with crisis' interchangeable with 'Vaso-Occlusive crisis (VOC).' n=7 events were Grade 3 or above in n=4 participants and did not meet the protocol definition of SAEs; Remainder n=46 in n=14 participants were mild/moderate severity. |
|
| Viral Upper Respiratory Tract Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated viral URTI; n=1 Grade 3 event in 1 participant (6months -2.99years); n=2 events in n=2 participants of mild/moderate severity. |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated pain in extremity; n=1 event Grade 3 in n=1 participant; n=4 events Grade \ |
|
| Acute Chest Syndrome (ACS) | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | ACS events of mild/moderate severity unrelated to IMP that did not meet the protocol definition of SAE. |
|
| Hypereosinophilic Syndrome | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Splenomegaly | Blood and lymphatic system disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Ear Pain | Ear and labyrinth disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Abdominal Discomfort | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Constipation | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Gastritis | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Gastrointestinal Haemorrhage | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Mouth Ulceration | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Salivary Gland Enlargement | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Teething | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Vomiting | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Feeling Abnormal | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Influenza Like Illness | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Injection Site Pain | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Injection Site Swelling | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Peripheral Swelling | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Pyrexia | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Swelling Face | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Ulcer | General disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Hepatomegaly | Hepatobiliary disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Drug Hypersensitivity | Immune system disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Body Tinea | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Chronic Sinusitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Conjunctivitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Conjunctivitis Viral | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| COVID-19 | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Croup Infectious | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Ear Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Fungal Skin Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Gastroenteritis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Gingival Abscess | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Gingivitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Hand-Foot-And-Mouth Disease | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Localised Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Lower Respiratory Tract Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Nasopharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Otitis Media | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Pharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Pharyngotonsillitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Rhinitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Sinusitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Tinea Capitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Tonsilitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Urinary Tract Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Viral Infection | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Viral Pharyngitis | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Viral Rash | Infections and infestations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Arthropod Bite | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Forearm Fracture | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Lip Injury | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Procedural Pain | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Skin Abrasion | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Skin Laceration | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Soft Tissue Injury | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Wound Complication | Injury, poisoning and procedural complications | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Aspartate Aminotransferase Increased | Investigations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Blood Iron Decreased | Investigations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Body Temperature Increased | Investigations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Platelet Count Increased | Investigations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Vitamin D Decreased | Investigations | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Vitamin D Deficiency | Metabolism and nutrition disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Bone Pain | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Muscle Tightness | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Soft Tissue Swelling | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Trismus | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Benign Rolandic Epilepsy | Nervous system disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Headache | Nervous system disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Lethargy | Nervous system disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Pica | Psychiatric disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Balanoposthitis | Reproductive system and breast disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Priapism | Reproductive system and breast disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Allergic Respiratory Disease | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Allergic Sinusitis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Bronchial Hyperreactivity | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Sneezing | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Skin Erosion | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Urticaria Papular | Skin and subcutaneous tissue disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Tooth Extraction | Surgical and medical procedures | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
| Toothache | Gastrointestinal disorders | MedDRA (23.1) | Systematic Assessment | Unrelated Treatment Emergent (TEAEs) of mild/moderate severity. |
|
Any publication or sub-set analysis of data based on the results obtained shall not be made before the first publication by the Sponsor, in which the Investigators may be named as authors. After initial publication material for public dissemination will be submitted to the Sponsor for review at least 60 days prior to submission, where all reasonable comments by the Sponsor will be incorporated. Sponsor may request additional delay for up to 6 months to protect proprietary information/IP.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Hussain Mulla, Head of Clinical Development | Nova Laboratories Ltd | 0116 223 0101 | hussain.mulla@novalabs.co.uk |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 21, 2022 | Dec 14, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| D006453 | Hemoglobinopathies |
| D013789 | Thalassemia |
| D006450 | Hemoglobin SC Disease |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
Not provided
Not provided
| ID | Term |
|---|---|
| D006918 | Hydroxyurea |
| D012996 | Solutions |
| ID | Term |
|---|---|
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D004364 | Pharmaceutical Preparations |
Not provided
Not provided
| Age Group (6 - 17.99 years) |
|
| Male |
|
| Sex: Female, Male (Age group 6 months - 1.99 years) |
|
|
| Sex: Female, Male (Age group 2 - 5.99 years) |
|
|
| Sex: Female, Male (Age group 6 - 17.99 years) |
|
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Ethnicity (Age Group 6 months - 1.99 years) |
|
|
| Ethnicity (Age Group 2 - 5.99 years) |
|
|
| Ethnicity (Age Group 6 - 17.99 years) |
|
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| Asian |
|
| Black or African American |
|
| Native Hawaiian or Other Pacific Islander |
|
| White |
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| Other (Specify): [sic] Caribbean |
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| Other (Specify): Black British |
|
| Race (Age Group 6 months - 1.99 years) |
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| Race (Age Group 2 - 5.99 years) |
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| Race (Age Group 6 - 17.99 years) |
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| HbSbeta0 |
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| SCA Type (Age Group 6 months - 1.99 years) |
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| SCA Type (Age Group 2 - 5.99 years) |
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| SCA Type (Age Group 6 - 17.99 years) |
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| Height (cm) Age Group (6 months - 1.99 years) |
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| Height (cm) Age Group (2 - 5.99 years) |
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| Height (cm) Age Group (6 - 17.99 years) |
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| Weight (kg) Age Group (6 months - 1.99 years) |
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| Weight (kg) Age Group (2 - 5.99 years) |
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| Weight (kg) Age Group (6 - 17.99 years) |
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