Trial Outcomes & Findings for Open-Label Extension Study of Reslizumab in Pediatric Subjects With Eosinophilic Esophagitis (NCT NCT00635089)

Open-Label Extension Study of Reslizumab in Pediatric Subjects With Eosinophilic Esophagitis

An AE was defined as any adverse experience, including side effect, injury, toxicity, sensitivity reaction, intercurrent illness, or sudden death, whether or not it was considered related to the use of study drug. Treatment emergent adverse events were those that started any time after the administration of the first dose of study drug (at baseline of this study) and before the cessation of study drug. Serious adverse events that occurred any time after the administration of the first dose of study drug until 30 days after administration of the last dose of study drug were reported as treatment emergent serious adverse events.

Hematology laboratory tests performed include: hemoglobin, hematocrit, red blood cell count, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cell count, and differential count and percentage (polymorphonuclear leukocytes \[neutrophils\], lymphocytes, eosinophils, monocytes, basophils, platelets).

Serum chemistry laboratory tests performed include: calcium, phosphorus, magnesium, sodium, potassium, chloride, creatinine, glucose \[nonfasting\], blood urea nitrogen, total cholesterol, uric acid, alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, gamma glutamyl transpeptidase, alkaline phosphatase, bicarbonate, creatine kinase, total protein, albumin, total bilirubin, direct bilirubin, indirect bilirubin. Urinalysis tests performed include: protein, glucose, ketones, bilirubin, urobilinogen, nitrite content, pH, specific gravity, white blood cells, microscopic (red blood cells, white blood cells, casts, crystals).

Low systolic blood pressure: \< 90 and decrease (↓) of 30 mm Hg from baseline (BL) (ages 5-18); high systolic blood pressure: \> 160 and increase (↑) of 30 mm Hg from BL (age 5-12), \> 130 and ↑ of 30 mm Hg from BL (age 13-18). Low diastolic blood pressure: \< 45 and ↓ of 12 mm Hg from BL (age 5-12), \< 55 and ↓ of 12 mm Hg from BL (age 13-18), \< 50 and ↓ of 15 mm Hg from BL; high diastolic blood pressure: \> 85 and ↑ of 12 mm Hg from BL (ages 5-18). Low heart rate: \< 80 and and ↓ of 30 beats per minute (bpm) from BL (age 5-12), \< 60 and and ↓ of 30 bpm from BL (age 13-18), \< 50 and and ↓ of 15 bpm from BL (age \> 18); high heart rate: \> 120 and ↑ of 30 bpm from BL (age 5-12), \> 100 and ↑ of 30 bpm from BL (age 13-18), \> 100 and ↑ of 15 bpm from BL (age \> 18). Low oral body temperature: \< 35.8° Celsius (age 5 to \>18); high oral body temperature: \> 38.1° C and ↑ 2° Celsius from BL (age 5-18).

HEENT=head, eyes, ears, nose and throat.

The infusion site was assessed before treatment and within 30 minutes after the end of the infusion at each monthly treatment visit (or at early withdrawal if before Week 16). The infusion site was graded according to a 5-point scale as follows: 0=no tenderness at IV site, no erythema, no swelling, no induration, no purulence, no palpable venous cord; 1=tender IV site, no erythema, no swelling, no induration, no purulence, no palpable venous cord; 2=tender IV site with erythema, some degree of swelling, no induration, no purulence, no palpable venous cord; 3=tender IV site with erythema and swelling, with induration or palpable venous cord, no purulence; 4=frank vein thrombosis, along with all signs of grade 3 with purulence; IV may stop running because of thrombosis. After the 16-week visit, formal infusion site evaluations were not continued. However, any infusion site reactions were recorded as adverse events and graded as other adverse events.

Number of participants receiving therapeutic classes of concomitant medications.

The mean change from baseline in esophageal eosinophil levels was described at week 16 or early withdrawal (if before week 16), using descriptive statistics. Baseline was defined as the last assessment before the first dose of reslizumab, which was the baseline of the double-blind study (NCT00538434) for patients who received reslizumab in the double blind study or the baseline of the open-label study for patients who received placebo during the double-blind study.

The data from the patient's/parent's eosinophilic esophagitis (EoE) Symptom Assessment were used to assess the shift from baseline in Predominant Symptom Assessment. The predominant symptom of the participant's/parent's EoE Symptom Assessment was selected at the double-blind baseline visit and remained the same throughout this study. Using the EoE Symptom Assessment, the participant/parent or legal guardian rated the severity of the previous week's EoE symptoms as none, mild, moderate, severe, or very severe on a 5-point scale. Only the predominant symptom selected for each participant contributed to the overall analysis of the Predominant Symptom Assessment and the subgroup analyses of individual symptoms. Thus, for the Predominant Symptom Analysis, some patients had dysphagia assessed, while others had either abdominal/chest pain or vomiting/regurgitation assessed.

The data from the participant's/parent's EoE Symptom Assessment, in combination with other observations, were used by physicians to determine the Physician's EoE Global Assessment. All components of the patient's EoE Symptom Assessment were used by physicians to determine the Physician's EoE Global Assessment.

The Child Health Questionnaire comprises 50 items. Specific items are recoded and/or recalibrated. Raw scores for scales (domains calculated over one or more items) are then calculated following set algorithms. The raw scales are then transformed to 0 to 100 scores, except for Change in Health which remains a 1-5 score. Finally two summary measures are calculated based on weighted combinations of selected scales. The Global Health, Physical Summary Score and Psychosocial Summary Score were summarized. For each, scores range from 0 (higher disease activity) to 100 (lower disease activity); higher scores indicate better health.

Number of participants answering that they either maintained or changed their diet from the beginning of the double-blind study (ie, NCT00538434). Additionally, for those participants who answered that they changed their diet from the beginning of the double-blind study (column 2), the number of participants in that group who changed by increasing the consistency of their food ('Increased consistency') and the percentage that changed by eating foods that previously worsened EoE ('Added foods'). (Note that these 2 categories are not mutually exclusive, so that someone could have both increased the consistency of the food they were eating AND also eaten foods that previously worsened their EoE symptoms.)

Reslizumab serum concentrations obtained in this study were included in ongoing and separate population pharmacokinetic analyses. The Number of Participants Analyzed reflects the number of participants who had concentrations measured following that dose level. Since some participants started on 1 mg/kg and later increased to 2 mg/kg (and are therefore represented in more than one column), the number of participants in each column add up to a greater number than the total in the overall column, which reflects the total number of participants with measurable concentration data in this study. The number of concentrations summarized for that dose level represents more than one concentration per participant in most cases.

Using a validated enzyme-linked immunosorbent assay (ELISA), the number of participants who had at least 1 confirmed positive value for ADA, either on day 0 after having received reslizumab in the double-blind study Res-05-0002 (NCT00538434) or during the course of the open-label study.