Efficacy and Safety of Oral Ibutamoren Mesylate in Prepubertal Children with Growth Hormone Deficiency: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study
- Trial ID
- 2025-523820-26-00
- Protocol
- LUM-201-10
- Sponsor
- Lumos Pharma LLC
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to evaluate the effect of 1.6 mg/kg/day of LUM 201 on growth rates in prepubertal children diagnosed with growth hormone deficiency over a 12-month period. The secondary objective includes the assessment of:
- Change from baseline in IGF-1 SDS, HT-SDS, and IGFBP-3 SDS.
Participants
This study involves 102 prepubertal participants diagnosed with growth hormone deficiency. The study population consists of both male and female patients within a specific age range, including girls aged 3.0 to 10.0 years and boys aged 3.0 to 11.0 years. Selection is based on several clinical requirements, including an IGF-1 standard deviation score of ≤ -1.0 and impaired height defined as ≥ 2.0 standard deviations below the mean according to WHO Growth Charts. Participants must be treatment-naïve and demonstrate a bone age delay of ≥ 12 months. Additionally, inclusion requires normal thyroid function and sufficient cortisol levels. For female participants, genetic testing is required to exclude Turner syndrome.
Plans and Procedures
This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study designed to evaluate the efficacy and safety of ibutamoren mesylate in prepubertal children diagnosed with growth hormone deficiency. The research methodology involves the administration of a 1.6 mg/kg daily oral dose of the test substance or a matched placebo. The trial duration for participant involvement is 12 months. The procedure begins with a screening visit to assess eligibility based on specific clinical criteria, including IGF-1 levels, growth hormone stimulation tests, and bone age assessments. Following screening, participants undergo a 12-month treatment period to monitor the primary endpoint of annual height velocity. Secondary endpoints include changes in IGF-1, height standard deviation scores, and IGFBP-3. The study concludes with an end-of-study visit to finalize assessments.
Treatment
The experimental medication is ibutamoren mesilate, an orphan drug provided in a capsule pharmaceutical form. The administration involves an oral route at a dosage of 1.60 mg/kg once per day to treat growth hormone deficiency.
The control group receives matched placebo capsules, which are administered orally once per day.
Efficacy
The primary efficacy assessment in this study is the change in Annualized Height Velocity (AHV) from Day 1 to Month 12 in subjects receiving either ibutamoren mesilate or a placebo.
Secondary efficacy parameters include:
- Change from baseline in insulin-like growth factor 1 standard deviation score (IGF-1 SDS)
- Change from baseline in height standard deviation score (HT-SDS)
- Change from baseline in insulin-like growth factor binding protein-3 standard deviation score (IGFBP-3 SDS)
- Absolute values for IGF-1 SDS, HT SDS, and IGFBP-3 SDS
Inclusion and Exclusion Criteria
Inclusion Criteria
- Written informed consent must be provided by the subject’s parent(s) or legally acceptable representative(s) prior to any study related procedures. Where applicable based on age and local regulations, the subject must also provide age-appropriate assent. The subject and the parent(s) or legally acceptable representative(s) must be willing and able to comply with all study procedures.
- Subjects must be naïve to treatment and prepubertal (Tanner stage I, which is determined by breast development in girls and testicular volume < 4.0 mL in boys).
- Subjects must have a maximal GH response of < 10 ng/mL from 2 prior GH stimulation tests conducted within the preceding 12 months. Acceptable GH stimulation tests include insulin, glucagon, arginine, clonidine and levodopa (L-DOPA). Additionally, 2 GH stimulation tests completed on the same day might be utilized, as well as other validated and approved GH stimulation tests at the discretion of the MM.
- Impaired height defined as ≥ 2.0 standard deviations (SDs) below the mean height for chronological age and sex at the Screening Visit according to the World Health Organization (WHO) Growth Charts.
- During the Screening Visit or within the preceding 3 months, subjects must exhibit a morning (prior to 9 a.m. local time) or random cortisol level of ≥ 7.0 µg/dL (193.0 nmol/L). If subjects have a morning or random cortisol response of < 7.0 µg/dL, they will need to undergo a stimulated cortisol test (adrenocorticotropic hormone [ACTH], insulin, glucagon) to qualify for the trial. The stimulated peak of cortisol response must be ≥ 18.0 µg/dL (500.0 nmol/L) for older polyclonal antibody assays. A stimulated peak less than 18 on newer-generation assays and considered normal (i.e. adrenally sufficient) will be acceptable after discussion with medical monitor group.
- At the Screening Visit, be age ≥ 3.0 years and age ≤ 10.0 years for girls and ≤ 11.0 years for boys.
- Have accurate baseline height velocity (HV) based on ≥ 6 months of growth assessments and confirmed by the MM establishing baseline HV < 25th percentile for age and sex. If only available prior assessments of growth were conducted 3 to 6 months prior to the Screening Visit, the MM should be contacted for consultation. Although it's preferable to conduct baseline height assessments using a wall-mounted stadiometer in the pediatric endocrinologist’s office, baseline AHV can be derived from data collected from the referral office.
- Undergo a BA assessment either during the Screening Visit or within 12 months prior. The assessment, interpreted using central reader methodology, must demonstrate a delay of ≥ 12 months compared to the chronological age.
- Girls should undergo genetic testing to eliminate the possibility of Turner syndrome. Additionally, if there are results from the short stature homeobox (SHOX) genetic test, they should indicate a negative outcome.
- Have normal thyroid function (TSH and free T4 in normal range). Subjects diagnosed with primary hypothyroidism must have documented euthyroid for ≥ 3 months prior to the Day 1 Visit.
- IGF-1 standard deviation score (SDS) ≤ -1.0 at the Screening Visit, compared to age and sex normalized range measured at central laboratory.
- IGF-1 concentration > 30.0 ng/mL (> 3.92 nmol/L) and a peak GH response of ≥ 5.0 ng/mL from the Screening Visit PEM test.
Exclusion Criteria
- Any medical or genetic condition which, in the opinion of the Investigator or MM, can be an independent cause of short stature and/or limit the response to growth hormone treatment (e.g. diabetes, idiopathic short stature [ISS; except in countries where ISS diagnostic criteria overlap with pediatric GHD criteria in the US], SHOX-deficiency, any chondrodysplasia, other named syndromes).
- An arm span to height ratio > 2 SDs below the mean for age and sex to rule out subclinical hypochondroplasia as an etiology for short stature (mesomelia).
- A medical or genetic condition that, in the opinion of the Investigator and/or MM, adds unwarranted risk to use of LUM-201.
- 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.
- Current inflammatory diseases requiring systemic corticosteroid treatment for > 2 consecutive weeks within the last 3 months prior to the Screening Visit. Children requiring inhaled glucocorticoid therapy at a dose of > 400.0 µg/day of inhaled budesonide or equivalents for > 4 consecutive weeks within the last 12 months prior to the Screening Visit.
- Use of hormone replacement therapy for any hormone deficiency other than stable primary thyroid hormone deficiency.
- Any ECG at the Screening Visit noted to have a clinically significant abnormality, as confirmed by the MM.
- The presence of any circumstance likely to prevent successful completion of this trial.
- Any subjects suspected of having past or present intracranial tumor growth as confirmed by brain imaging prior to the Screening or Day 1 Visit. Nonspecific abnormalities should be discussed with the MM.
- Any subject suspected of having intracranial hypertension (IH) as confirmed by fundoscopy and other assessments. Signs and symptoms of IH should be discussed with the MM.
- Any subject with serum alanine transaminase (ALT), aspartate transaminase (AST), or total bilirubin > upper limit of normal (ULN).
- Multiple pituitary hormone deficiencies.
- Prior treatment with growth factors including, but not limited to, GH, IGF-1, and GH secretagogues. (These may be used for limited time as a diagnostic test.)
- Suspicion of absent pituitary function as evidenced by a maximal stimulated GH ≤ 3.0 ng/mL on any prior standard of care GH stimulation test completed within 12 months, or pituitary deficiencies beyond GH.
- Malnutrition as determined by the Investigator based on clinical findings, medical history and laboratory findings.
- Body weight ≤ 14.0 kg.
- BMI < -2 or > +2 SDs for age and sex based on WHO standards.
- Birth weight for gestational age < 3rd percentile based on WHO or local standards.
- Participation in any therapeutic trial of investigational drug(s) within 6 months prior to the Screening visit.
- Known or suspected allergy to LUM-201, placebo, or one of their excipients.
- Unwilling to accept randomization assignment.
- Treatment with medications known to be moderate or strong inhibitors or strong inducers of cytochrome P450 (CYP) 3A/4.
- Treatment with medications known to be predominantly metabolized (< 5% contribution by other isoforms) by either CYP3A/4, 2C8, 2C9, or 2C19.
- Treatment with medications known to act as strong inhibitors of P-glycoprotein (P-gp), potent substrates of P-gp, or multidrug and toxin extrusion protein 1.
- History of spinal, cranial, or total body irradiation.
- History or presence of malignant disease; any evidence of present tumor growth.
- Children with psychosocial short stature.
- Closed epiphyses.
- Attention deficit hyperactivity disorder (ADHD) diagnosis, regardless of treatment.>
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 01 Mar 2026 | 12 |
 Italy | Not Yet Recruiting | 01 Mar 2026 | 9 |
 Poland | Not Yet Recruiting | 01 Mar 2026 | 12 |
 Romania | Not Yet Recruiting | 01 Mar 2026 | 12 |
 Spain | Not Yet Recruiting | 01 Mar 2026 | 12 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Ibutamoren Mesylate | Test | CAPSULE | ORAL | 1.60 | 12 | PRD12917985 |
Ibutamoren Mesylate | Test | CAPSULE | ORAL | 1.60 | 12 | PRD12917983 |
Matched placebo capsules administered orally once per day | Placebo | N/A | — | — | — | N/A |
Ibutamoren Mesylate | Test | CAPSULE | ORAL | 1.60 | 12 | PRD12917984 |