IGF-1 Treatment for Individuals With Short Stature Due to PAPP-A2 Deficiency

Height velocity in a patient with PAPP-A2 deficiency treated with rhIGF-1 for five years (when the patient elected to discontinue treatment after reviewing growth velocity and skeletal maturation). Ultimately only one patient was treated for the study duration with results reported, as the other recruited participant (sibling of the treated patient) experienced pseudotumor cerebri and discontinued treatment after 51 days. He nevertheless was followed, with height velocity also reported.

Height Standard Deviation Score is the standard deviation above or below the mean the height is for age and gender. Values were obtained by plotting heights on Centers for Disease Control and Prevention growth charts. An increase in Height Standard Deviation Score correlates with increase in height. Results are reported for the participant with PAPP-A2 deficiency treated with rhIGF-1, as well as sibling who did not continue treatment with rhIGF-1.

Assess the PK/PD relationship (PD marker being IGFBP-3) annually while on treatment with rhIGF-1

Observe nonparametric measures of glucose pre and post ongoing treatment with rhIGF-1. Oral glucose tolerance tests (OGTT) were performed annually during the five-year treatment period at pre-treatment (baseline) and post-initiation of treatment (after 12 months, 24 months, 36 months, 48 months, and 60 months).

Observe nonparametric measures of insulin metabolism in each individual pre (baseline) and post ongoing treatment with rhIGF-1. Oral glucose tolerance testing (OGTT) was performed pre-treatment (baseline) and post-treatment (after 12 months, 24 months, 36 months, 48 months, and 60 months).

Observe nonparametric measures of body composition pre (baseline) and post ongoing treatment with rhIGF-1 (assessed after 12 months, 24 months, 36 months, 48 months, and 60 months of rhIGF-1 treatment). BMI percentiles were determined utilizing Centers for Disease Control and Prevention growth charts.

Observe nonparametric measures of body composition pre (baseline) and post ongoing treatment with rhIGF-1 (assessed after 12 months, 24 months, 36 months, 48 months, and 60 months of rhIGF-1 treatment). Body fat content and lean body mass were evaluated with dual energy x-ray absorptiometry.

Observe nonparametric measures of body composition pre (baseline) and post ongoing treatment with rhIGF-1 (assessed after 12 months, 24 months, 36 months, 48 months, and 60 months of rhIGF-1 treatment). Body fat content and lean body mass were evaluated with dual energy x-ray absorptiometry.

Observe nonparametric measures of bone turnover pre-treatment (baseline) and post initiation of ongoing treatment (at 12 months, 24 months, 36 months, 48 months, and 60 months) while on rhIGF-1

Observe nonparametric measures of bone density at baseline (pre-treatment) and post initiation of ongoing treatment with rhIGF-1. Dual energy x-ray absorptiometry (DXA) was performed of total body less head, lumbar spine, hip, and forearm. Results are reported as height adjusted z-scores for age and gender, commonly done for bone density. A z-score of 0 is equivalent to population mean, positive above the mean, and negative below the mean. Z-scores within 2 standard deviations of the mean (Z-score 2 to -2) are generally considered normal, however are not sufficient to comment on presence or absence of osteoporosis in the pediatric population.

This was a pharmacokinetic assessment in regards to rhIGF-1 completed in siblings with PAPP-A2 deficiency, Participants received a 120 mcg/kg dose of rhIGF-1 (Increlex). Pharmacokinetic measurements were obtained over 24 hours. To isolate the effect of injected rhIGF-1, baseline-corrected concentrations were included by subtracting baseline concentration from measured concentrations. Results reported include maximum corrected total IGF-I and free IGF-I. Due to constraints of reporting platform, time to maximum values and area under the curve (AUC) 12 hours after the dose are reported as separate outcomes.

This was a pharmacokinetic assessment in regards to rhIGF-1 completed in siblings with PAPP-A2 deficiency, Participants received a 120 mcg/kg dose of rhIGF-1 (Increlex). Pharmacokinetic measurements were obtained over 24 hours. To isolate the effect of injected rhIGF-1, baseline-corrected concentrations were included by subtracting baseline concentration from measured concentrations. Results reported include time to maximum corrected total IGF-I and free IGF-I. Due to constraints of reporting platform, maximum corrected total IGF-I and free IGF-I values and area under the curve (AUC) 12 hours after the dose are reported as separate outcomes.

This was a pharmacokinetic assessment in regards to rhIGF-1 completed in siblings with PAPP-A2 deficiency, Participants received a 120 mcg/kg dose of rhIGF-1 (Increlex). Pharmacokinetic measurements were obtained over 24 hours. To isolate the effect of injected rhIGF-1, baseline-corrected concentrations were included by subtracting baseline concentration from measured concentrations. Results reported include area under the curve (AUC) 12 hours after the dose. Due to constraints of reporting platform, maximum corrected total IGF-I and free IGF-I, as well as time to maximum values separate outcomes.