A Pivotal, Parallel-Arm, Phase 3, Open-Label, Active-controlled, Global, Multicenter, Randomized Basket Trial Investigating the Efficacy and Safety of Once-weekly Lonapegsomatropin Compared to Daily Somatropin in Prepubertal Children and Adolescents With Growth Failure or Short Stature Due to Growth Hormone Sufficient Disorders - Turner Syndrome, SHOX Deficiency, Small for Gestational Age, and Idiopathic Short Stature

Plain English Summary

Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders is a Phase 3 clinical trial sponsored by Ascendis Pharma A/S studying Turner Syndrome, Short Stature Homeobox Gene Mutation, Idiopathic Short Stature, Small for Gestational Age at Delivery. Tests how well once-weekly lonapegsomatropin works compared to daily somatropin for children with growth failure or short stature due to specific disorders. For children aged 2 to 17 with Turner Syndrome, SHOX Deficiency, Small for Gestational Age, or Idiopathic Short Stature. Participation involves receiving either lonapegsomatropin once a week or somatropin daily for 2 years. Alternative treatments include daily somatropin, but this study focuses on comparing lonapegsomatropin's effectiveness and safety. The trial aims to enroll 186 participants.

Official Summary

This basket trial will enroll prepubertal children and adolescents with clinically diagnosed and genetically confirmed (if applicable) TS, SHOX-D, SGA, or ISS between ages of ≥2 and \<18 years with open growth plates. The purpose of the study is to see how well treatment with once-weekly lonapegsomatropin works compared to treatment with daily somatropin. Approximately 186 participants will be distributed equally (1:1), to receive either lonapegsomatropin for 2 years or somatropin for 1 year followed by lonapegsomatropin for 1 year. This trial will be conducted in the United States, France, Germany, Italy, Romania, Spain and South Korea.

Who Can Participate

Here is what you need to know about eligibility for this trial. Can join if you are between 2 and 17 years old, have a specific growth disorder, and are prepubertal. Cannot join if you have closed epiphyses, advanced bone age, or certain medical conditions like diabetes or sleep apnea. Age requirement: 2 to 17 years. Health requirements: Prepubertal, specific growth disorders, and no closed epiphyses. This trial is studying Turner Syndrome, Short Stature Homeobox Gene Mutation, Idiopathic Short Stature, Small for Gestational Age at Delivery, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures mean that patients will see how well their height grows over time with the treatment. The specific primary outcome measures are: Annualized Height Velocity (AHV) (cm/year) (52 Weeks). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial fills a gap by comparing the efficacy and safety of once-weekly lonapegsomatropin to daily somatropin for children with specific growth disorders. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Turner Syndrome, Short Stature Homeobox Gene Mutation, Idiopathic Short Stature, Small for Gestational Age at Delivery, where improved treatment options are needed.

Investor Insight

The market size for growth hormone treatments is large, with this trial potentially offering a more convenient option for patients. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if you have a specific growth disorder and are prepubertal. Participation involves receiving either lonapegsomatropin once a week or somatropin daily for 2 years. This trial is currently recruiting participants. The trial is being conducted at 7 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 186 participants

Interventions

• COMBINATION_PRODUCT: Lonapegsomatropin [SKYTROFA®] — Subcutaneous injection once weekly
• COMBINATION_PRODUCT: Somatropin Pen Injector — Subcutaneous injection once daily

Primary Outcomes

• Annualized Height Velocity (AHV) (cm/year) (52 Weeks)

Secondary Outcomes

• Annualized Height Velocity (AHV) (cm/year) (104 Weeks)
• Change from baseline in height standard deviation score (SDS) (52 Weeks and 104 Weeks)
• Change from baseline in Bone Age (years) (52 Weeks and 104 Weeks)
• Change from baseline in ratio of Bone Age/chronological age (52 Weeks and 104 Weeks)
• Number of participants with treatment-related adverse events (AEs) (52 Weeks and 104 Weeks)

Full Eligibility Criteria

Inclusion Criteria:

1. Chronological age between ≥2 and \<18 years, at start of screening.
2. Naïve to growth hormone and growth hormone promoting therapies.
3. Prepubertal.
4. Able to stand without assistance.
5. Diagnosis of TS, SHOX-D, SGA, or ISS with impaired growth or short stature, according to the following disease-specific criteria:

   TS or SHOX-D (Léri-Weill dyschondrosteosis):
   1. Diagnosis confirmed by a genetic test. NOTE: Historical test results are acceptable for proof of diagnosis. For karyotypes, a minimum of 20 cells must be counted.
   2. Impaired growth or short stature defined as:

   (i.) AHV \<25th percentile over a time span of 6-16 months prior to screening utilizing a historical height properly documented in a health care setting (self-measurement record is not accepted) OR (ii.) Height \<5th percentile for sex and age according to the Centers for Disease Control Growth Charts for the United States

   SGA without catch-up growth:

   c. Birth weight and/or birth length \< -2.0 SDS for gestational age according to the 2006 World Health Organization Child Growth Standards. For infants born premature, the Fenton Preterm Infant Growth Chart (Fenton 2013) should be used.

   d. Impaired growth or short stature defined as: (i.) AHV \<25th percentile over a time span of 6-16 months prior to screening properly documented in a health care setting (self-measurement record is not accepted) OR (ii.) Height \< -2.0 SDS for age and sex according to the 2000 Centers for Disease Control Growth Charts for the United States for children ≥ 3 years or height \< -2.5 SDS for age and sex according to the for children ≥ 2 years and \< 3 years

   ISS:

   e. Height \< -2.25 SDS for sex and age according to the Centers for Disease Control Growth Charts for the United States with no identifiable cause for short stature.

   f. Documented normal GH-IGF-1 axis, defined as either: (i.)IGF-1 SDS \>0 at screening based on central laboratory OR (ii.)Historical documentation of normal peak GH upon stimulation test (as defined by local institution) g. 46,XX chromosome as determined by karyotype or microarray if female. For karyotypes, a minimum of 30 cells must be counted.
6. If on hormone replacement therapies for any hormone deficiencies other than growth hormone (e.g., adrenal, thyroid), must be on adequate and stable doses for ≥4 weeks prior to and throughout screening.
7. Written, signed informed consent provided by parent(s) or legal guardian(s) of the participant. Assent should be signed by participant as required by IRB/HREC/IEC.

Exclusion Criteria:

1. Advanced bone age X-ray by central reading defined as \>20% above chronological age in months (Greulich 1959).
2. Closed epiphyses as defined as bone age of ≥14.0 years in females or ≥16.0 years in males.
3. Current clinical diagnosis of diabetic retinopathy
4. Any diagnosis or presence at screening of the following:

   1. Untreated moderate or severe sleep apnea as determined by formal (local) read of an inpatient or at-home sleep study.
   2. Prader Willi syndrome with severe obesity, history of severe upper airway obstruction, or severe respiratory impairment.
5. Signs/symptoms of intracranial hypertension, active proliferative retinopathy.
6. Uncontrolled hypo- or hyperthyroidism.
7. Uncontrolled diabetes mellitus (defined as: HbA1c \>7.5% from central laboratory at screening).
8. Known history or diagnosis of any gastrointestinal inflammatory condition, HIV, radiation exposure, other skeletal dysplasias, growth hormone deficiency, and/or cardio-thoracic surgery due to their independent effects on growth.
9. Any significant hepatic or renal abnormality, such as abnormal renal function (defined as eGFR \<60 mL/min/1.73m2).
10. Undiagnosed or uncontrolled hypertension.
11. Receiving treatment with any agent that might influence growth or interfere with GH secretion or action including any sex steroids and stimulants for attention-deficit/hyperactivity disorder (ADHD).
12. High dose inhaled glucocorticoid for more than 28 consecutive days total over the course of 12 months.
13. Female who is pregnant, plans to be pregnant, or breastfeeding.
14. Participation in another interventional clinical trial involving an investigational compound within 90 days prior to screening or in parallel to this trial.
15. Any disease or condition that, in the judgement of the investigator, may make the participant unlikely to comply with the requirements of the protocol or any condition that presents undue risk from the investigational product or trial procedures.
16. Exclusion Criteria only applicable to TS:

    1. Presence of Y chromosome material on genetic testing without history of gonadectomy.
    2. Less than 10% of 45,X mosaicism.
    3. Any known, clinically significant, congenital or acquired cardiovascular dysfunction that might interfere with growth.
17. Exclusion Criteria only applicable to SGA:

    a. Any known clinically significant abnormality likely

Trial Locations

• Ascendis Pharma Investigational Site, Centennial, Colorado, United States
• Ascendis Pharma Investigational Site, Orlando, Florida, United States
• Ascendis Pharma Investigational Site, Atlanta, Georgia, United States
• Ascendis Pharma Investigational Site, Idaho Falls, Idaho, United States
• Ascendis Pharma Investigational Site, Saint Paul, Minnesota, United States
• Ascendis Pharma Investigational Site, Oklahoma City, Oklahoma, United States
• Ascendis Pharma Investigational Site, San Antonio, Texas, United States

Frequently Asked Questions

Related Conditions

• Turner Syndrome
• Short Stature Homeobox Gene Mutation
• Idiopathic Short Stature
• Small for Gestational Age at Delivery
• Growth Hormone Sufficient Disorders
• Growth Failure
• Growth Hormone Insensitivity
• Growth Hormone Resistance
• Growth Hormone Deficiency
• Growth Hormone Receptor Mutations

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