Investigating Efficacy and Safety of Once-weekly NNC0195-0092 Treatment Compared to Daily Growth Hormone Treatment (Norditropin® FlexPro®) in Growth Hormone Treatment naïve Pre-pubertal Children With Growth Hormone Deficiency

Novo Nordisk

Status and phase: Completed; Phase 2

Conditions: Growth Hormone Deficiency in Children; Growth Hormone Disorder

Treatments: Drug: Norditropin® FlexPro® pen; Drug: somapacitan

Study type: Interventional

Funder types: Industry

Identifiers

NCT02616562

U1111-1166-7062 (Other Identifier)

NN8640-4172

2015-000531-32 (EudraCT Number)

Details and patient eligibility

About

This trial is conducted globally. The aim of the trial is to investigate efficacy and safety of once-weekly NNC0195-0092 treatment compared to daily growth hormone treatment (Norditropin® FlexPro®) in growth hormone treatment naïve pre-pubertal children with growth hormone deficiency.

The main trial period will consist of 26 weeks of treatment, followed by a 26 week extension period.

Enrollment: 76 patients

Sex: All

Ages: 2 to 10 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Boys: Tanner stage 1 for pubic hair and testis volume below 4 ml , age at least 2 years and 26 weeks and below or equal to 10.0 years at screening
• Girls: Tanner stage 1 for breast development (no palpable glandular breast tissue) and pubic hair, age at least 2 years and 26 weeks and below or equal to 9.0 years at screening
• Confirmed diagnosis of GHD (growth hormone deficiency) within 12 months prior to screening as determined by two different GH (growth hormone) stimulation tests, defined as a peak GH level of below or equal to 7.0 ng/ml. For children with three or more pituitary hormone deficiencies only one GH stimulation test is needed
• No prior exposure to GH therapy and/or IGF-I (insulin-like growth factor I) treatment
• Height of at least 2.0 standard deviations below the mean height for chronological age (CA) and gender according to the standards of Centers for Disease Control and Prevention 2-20 years: Girls/Boys stature-for-age and weight-for-age percentiles CDC at screening
• Annualized height velocity (HV) below the 25th percentile for CA (chronological age) and gender or below -0.7 SD (standard deviation) score for CA and sex, according to the standards of Prader calculated over a time span of minimum 6 months and maximum 18 months

Exclusion criteria

• Any clinically significant abnormality likely to affect growth or the ability to evaluate
• growth with standing measurements: Chromosomal aneuploidy and significant gene mutations causing medical "syndromes" with short stature, including but not limited to Turner syndrome, Laron syndrome, Noonan syndrome, or absence of GH receptors. Congenital abnormalities (causing skeletal abnormalities), including but not limited to Russell-Silver Syndrome, skeletal dysplasias. Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants
• Children born small for gestational age (SGA - birth weight and/or birth length below-2 SD for gestational age)
• Concomitant administration of other treatments that may have an effect on growth, including but not limited to methylphenidate for treatment of attention deficit hyperactivity disorder (ADHD)
• Prior history or presence of malignancy and/or intracranial tumour

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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76 participants in 5 patient groups

Cohort I Norditropin/somapacitan

Experimental group

Description:

Participants received Norditropin subcutaneously daily in main trial period, extension trial period and safety extension trial period. After completing the safety extension trial period (week 156), participants who received Norditropin were allocated to open-labelled Somapacitan dose 3 subcutaneously once weekly for the 208-week (up till week 364) long-term safety extension period. After week 364, participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.

Treatment:

Drug: somapacitan

Drug: Norditropin® FlexPro® pen

Cohort I somapacitan pooled

Experimental group

Description:

Participants were randomized (1:1:1) to receive Somapacitan treatment (dose 1/dose 2/dose 3) subcutaneously once-weekly during the 26-week main trial period and the 26-week extension trial period. After completing the main and extension trial periods (week 52), all participants initially randomized to double-blinded Somapacitan received open-labelled Somapacitan dose 3 for the 104-week safety extension trial period. After completing the safety extension trial period (week 156), all participants in cohort I were allocated to open-labelled somapacitan dose 3 for the 208-week (up till week 364) long-term safety extension period. In extension after week 364 period participants received somapacitan dose 3 subcutaneously once weekly until somapacitan was available for prescription for children with GHD in their country or until August 2024, at the latest.

Treatment:

Drug: somapacitan

Cohort II somapacitan previously treated

Experimental group

Description:

Participant who was previously treated with GH (Growth hormone) prior to enrollment in the trial at week 156, received somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.

Treatment:

Drug: somapacitan

Cohort III somapacitan treatment naive

Experimental group

Description:

Participants who were naive to treatment with GH prior to enrolment in the trial at week 156, received open-labelled somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.

Treatment:

Drug: somapacitan

Cohort III somapacitan previously treated

Experimental group

Description:

Participants who were previously treated with GH prior to enrollment in the trial at week 156, received open-labelled somapacitan dose 3 subcutaneously once weekly until it was available for prescription in participants' respective countries or until August 2024, at the latest.

Treatment:

Drug: somapacitan