A Safety, Tolerability and Efficacy Study of TransCon hGH in Children With Growth Hormone Deficiency

Ascendis Pharma Endocrinology Division A/S146 enrolled

Overview

A 26 week trial of TransCon hGH, a long-acting growth hormone product, administered once-a-week. Approximately 150 children (males and females) with growth hormone deficiency (GHD) will be included. All study participants will receive TransCon hGH. This is a global trial that will be conducted in, but not limited to, the United States, Canada, Australia, and New Zealand.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

146

Conditions

Growth Hormone Deficiency, Pediatric Endocrine System Diseases Hormone Deficiency Pituitary Diseases

Interventions

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Investigator-determined GHD diagnosis prior to the historical initiation of daily hGH therapy. 2. 6 months to 17 years old, inclusive, at Visit 1 1. If 3 to 17 years old, are taking daily hGH at a dose of ≥ 0.20 mg hGH/kg/week for at least 13 weeks but no more than 130 weeks prior to Visit 1 2. If ≥ 6 months but \< 3 years old, are either hGH treatment-naïve or are taking daily hGH at a dose of ≥ 0.20mg hGH/kg/week for no more than 130 weeks prior to Visit 1 3. Tanner stage \< 5 at Visit 1 4. Open epiphyses (bone age ≤14.0 years for females or ≤16.0 years for males) 5. Written, signed, informed consent of the parent or legal guardian of the subject and written assent of the subject as required by the IRB/HREC/IEC Exclusion Criteria: 1. Weight of \< 5.5 kg or \> 80 kg at Visit 1 2. Females of child-bearing potential 3. History of malignant disease 4. Any clinically significant abnormality likely to affect growth or the ability to evaluate growth (eg, chronic diseases or conditions such as renal insufficiency, spinal cord irradiation, hypothyroidism, active celiac disease, malnutrition or psychosocial dwarfism) 5. Poorly-controlled diabetes mellitus (HbA1c \>8.0%) or diabetic complications 6. Known neutralizing antibodies against hGH 7. Major medical conditions, unless approved by Medical Monitor 8. Pregnancy 9. Presence of contraindications to hGH treatment 10. Likely to be non-compliant with respect to trial conduct (in regards to the subject and/or the parent/legal guardian/caregiver) 11. Participation in any other trial of an investigational agent within 30 days prior to Visit 1 12. Prior exposure to investigational hGH

Locations (24)

University of Alabama

Birmingham, Alabama, United States

Neufeld Medical Group Inc.

Los Angeles, California, United States

Center of Excellence in Diabetes and Endocrinology

Sacramento, California, United States

Rocky Mountain Pediatric Endocrinology

Centennial, Colorado, United States

Nemours Children's Health System

Jacksonville, Florida, United States

Orlando Health Inc.

Orlando, Florida, United States

Tallahassee Memorial Hospital

Tallahassee, Florida, United States

University of Iowa

Iowa City, Iowa, United States

Children's Minnesota

Saint Paul, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

...and 14 more locations

Outcomes

Primary Outcomes

Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability]

Safety and tolerability of weekly lonapegsomatropin (TransCon hGH) treatment

Time frame: 26 weeks

Secondary Outcomes

Annualized Height Velocity (AHV) at 26 Weeks of Weekly Lonapegsomatropin Treatment

Annualized height velocity (AHV) at 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. The AHV at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.

Time frame: 26 weeks

Number of Subjects With IGF-1 Standard Deviation Score (SDS) in the Range of 0.0 to +2.0 at 26 Weeks of Weekly Lonapegsomatropin Treatment

IGF-1 Standard Deviation Score (SDS) is the number of standard deviations above or below the mean Insulin-like Growth Factor 1 (IGF-1) level for age and sex. IGF-1 SDS was derived using the LMS method as ((IGF-1/M)\^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from Bidlingmaier et al. (2014). A Standard Deviation Score of 0 represents the population mean.

Time frame: 26 weeks

Change in Height Standard Deviation Scores (SDS) at 26 Weeks of Weekly Lonapegsomatropin Treatment

Height Standard Deviation Score (SDS) is the number of standard deviations above or below the mean height for age and sex. Height SDS was derived using the LMS method as ((Height/M)\^L)-1)/(L x S), where M = median, S = generalized coefficient of variation, and L = power in the Box-Cox transformation, the M, S, L values were obtained from 2000 CDC growth charts for the United States. A Standard Deviation Score of 0 represents the population mean. A higher change from baseline in Height SDS indicates a better outcome. The height SDS change from baseline at each visit was modeled using ANCOVA adjusting for baseline age, peak GH levels (log transformed) at diagnosis, delta average-parental height SDS, prior GH dose level (log transformed), and prior GH dose duration (log transformed) as covariates and gender as a factor. Subjects who did not take prior GH treatment were not included in the model.

Time frame: Baseline and 26 weeks

Number of Participants With Treatment Emergent Anti-hGH Binding Antibody Formation

Number of participants with treatment emergent anti-hGH antibodies over 26 weeks of weekly lonapegsomatropin (TransCon hGH) treatment. All samples were negative for anti-hGH neutralizing antibodies.

Time frame: 26 weeks