Phase 2 Study of LUM-201 in Children With Growth Hormone Deficiency (OraGrowtH210 Trial)

Study Overview
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Brief Summary
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This is a multi-national trial. The goals of the trial are to study LUM-201 as a possible treatment for Pediatric Growth Hormone Deficiency (PGHD) and investigate a predictive enrichment marker (PEM) strategy to select subjects likely to respond to therapy with LUM-201.

Detailed Description
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This trial will have one screening visit with tests to assess if subjects are eligible to start study therapy. Once subjects have completed screening, and if they are determined to be eligible, they will be randomized to receive one of three oral daily doses of LUM-201 or daily injections of recombinant human growth hormone (rhGH). All subjects will have an equal chance of being placed in any of the four groups. The trial consists of up to 24 months of treatment. After screening, subjects will return to the clinic for 6 (subjects placed in rhGH group) or 10 visits (subjects placed in LUM-201 group). During several of these clinic visits, subjects will have a physical exam, blood, and urine collections. There will also be 3 phone calls with study staff that will take place between the clinic visits.

Official Title
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A Multicenter, 24-Month, Randomized, Open-Label, Active Control, Parallel Arm, Phase 2 Study of Daily Oral LUM-201 in Naïve-to-Treatment, Prepubertal Children With Idiopathic Growth Hormone Deficiency (GHD)

Conditions
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Growth Hormone Deficiency

Intervention / Treatment
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* Drug: LUM-201
* Drug: rhGH Norditropin® pen (34 µg/kg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an established diagnosis of idiopathic PGHD as determined by standard diagnostic criteria. Eligible subjects must be naïve-to-treatment and be prepubertal. Morning cortisol ≥ 7 µg/dL or stimulated cortisol ≥ 14 µg/dL. At Screening, be ≥ 3.0 years and ≤ 11.0 years for girls and ≤ 12.0 years for boys. Have HT-SDS ≤ -2.0 or HT-SDS ≥ 2 SD below mean parental HT-SDS. Have a baseline height velocity < 5.5 cm/year based on at least 6 months of growth. Have a bone age delayed by ≥ 6 months with respect to chronological age. Have prepubertal status as evidenced by Tanner Stage I breast development in girls and testicular volume < 4.0 mL in boys. In girls, have genetic testing results to rule out Turner syndrome. If SHOX genetic testing results are available, they need to be negative. Have normal thyroid function. Subjects diagnosed with hypothyroidism must have documented successful treatment for at least 30 days prior to Day 1. Exclusion Criteria: Any medical or genetic condition which, in the opinion of the Investigator or Medical Monitor (MM), can be an independent cause of short stature and/or limit the response to exogenous growth factor treatment. (Examples: diabetes, idiopathic short stature). A medical or genetic condition that, in the opinion of the Investigator and/or MM, adds unwarranted risk to use of LUM-201 or rhGH. Use of any medication that, in the opinion of the Investigator and/or MM, can independently cause short stature or limit the response to exogenous growth factors (Example: glucocorticoids). Evidence or history of an intracranial mass (e.g., pituitary tumor, craniopharyngioma). Suspicion of absent pituitary function as evidenced by a maximal stimulated GH ≤ 3 ng/mL on two prior standard of care GH stimulation tests, or pituitary deficiencies beyond GH and thyroid function. Malnutrition as evidenced by medical history or a body weight < 3rdth percentile for current height. BMI > 95th percentile. Gestational age-adjusted birth weight < 5th percentile (small for gestational age). History of spinal, cranial, or total body irradiation. Treatment with medications known to act as moderate or strong inhibitors or strong inducers of CYP3A/4, or with medications known to act as strong inhibitors of P-glycoprotein (P-gp) or potent substrates of P-gp or Multidrug and toxin extrusion protein 1 (MATE1).

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LUM-201 (0.8 mg/kg/day)<br> | Drug: LUM-201<br>* Administered orally once daily<br>|
| Experimental: LUM-201 (1.6 mg/kg/day)<br> | Drug: LUM-201<br>* Administered orally once daily<br>|
| Experimental: LUM-201 (3.2 mg/kg/day)<br> | Drug: LUM-201<br>* Administered orally once daily<br>|
| Active Comparator: rhGH (34 µg/kg/day)<br> | Drug: rhGH Norditropin® pen (34 µg/kg)<br>* Administered subcutaneously (s.c., under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects selected by PEM strategy who meet target growth | Annualized height velocity (AHV) measured as standing height with stadiometer | Day 1 to Month 6 | 
| AHV after 6 months on LUM-201 compared to rhGH | Annualized height velocity to be measured | Day 1 to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Degree of concordance between the first and second assessment with the PEM strategy. | Peak serum concentration of GH in response to a single provocative dose of LUM-201 | Screening to Day 1 | 
| Incidence of adverse events in children with GHD | Number of events | Day 1 to Month 24 | 
| Height standard deviation score (SDS) | Change in HT-SDS | Day 1 to Month 6 and Month 12 | 
| Height velocity standard deviation score (HV-SDS) | Change in HV-SDS | Day 1 to Month 6, and Month 12 | 
| Change in Weight | Change in Weight | Day 1 to Month 6, and Month 12 | 
| Change in Weight SDS | Change in Weight-SDS | Day 1 to Month 6 and Month 12 | 
| Change in BMI | Change in BMI | Day 1 to Month 6 and Month 12 | 
| Change in BMI SDS | Change in BMI SDS | Day 1 to Month 6 and Month 12 | 
| Bone Age | Change in bone age, measured by X-ray of left hand and wrist using Greulich & Pyle atlas | Day 1 to Month 6 and Month 18 | 
| Pharmacokinetics of LUM-201 | Serum concentrations (Cmax/Steady State) | Day 1 to Month 6 and 12 | 
| GH Concentration on maintenance treatment | Serum GH concentration | Day 1 to Month 6 and 12 | 
| Insulin-like growth factor 1 SDS | Serum concentrations of insulin-like growth factor 1 | Day 1 to Month 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GHD, Pediatric Growth Hormone Deficiency, LUM-201, Growth hormone secretagogue, Height, Catch-up growth, PEM, Oral, Predictive Enrichment Marker