Growth Hormone Deficiency
Conditions
Keywords
GHD, Pediatric Growth Hormone Deficiency, LUM-201, Growth hormone secretagogue, Height, Catch-up growth, PEM, Oral, Predictive Enrichment Marker
Brief summary
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
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.
Interventions
DRUGLUM-201
Administered orally once daily
DRUGrhGH Norditropin® pen (34 µg/kg)
Administered subcutaneously (s.c., under the skin) once daily.
Sponsors
Lumos Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Positive Growth Response From Day 1 to Month 6 (AHV >= 6.85 cm/yr) | Day 1 to Month 6 | Annualized height velocity (AHV); Height is measured in triplicate, by a calibrated stadiometer and taking the mean value AVH equation is (h2-h1/t2-t1)\*365.25; h1 = height measured at day 1 h2 = height measured at month 6 t1 = day 1 t2 = month 6 |
| AHV After 6 Months on LUM-201 Compared to rhGH | Day 1 to Month 6 | Annualized height velocity to be measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Positive Result on Both PEM Tests (at Screening and on Day 1) | Screening to Day 1 | PEM Test Reproducibility Safety Population |
| Change in Height Standard Deviation Score (SDS) | Day 1 to Month 6 | Full Analysis Set Population month 6 |
| Change in Weight From Baseline | Day 1 to Month 6 | Change in Weight from baseline |
| Change in Weight SDS | Day 1 to Month 6 | Change in Weight-SDS (Standard Deviation Score) |
| Change in Body Mass Index (BMI) | Day 1 to Month 6 | Change in BMI from baseline |
| Change in BMI | Day 1 to Month 12 | Change in BMI (Body Mass Index) from baseline |
| Change in BMI SDS | Day 1 to Month 6 | Change in BMI SDS |
| Bone Age | Day 1 to Month 6 | Change in bone age, measured by X-ray of left hand and wrist using Greulich \& Pyle atlas |
| Pharmacokinetics of LUM-201 | Day 1 to Month 6 | Serum concentrations at 30 minutes (Cmax/Steady State) |
| Growth Hormone (GH) Concentration on Maintenance Treatment | Month 6 | Serum GH concentration |
| Insulin-like Growth Factor 1 SDS | Month 6 | Serum concentrations of insulin-like growth factor 1 This is not a Z-Score analysis. Standard deviation score of 0 is the population mean for the age/sex. Normal range is typically -2 to +2 SDS. A positive score is an improvement and a negative score a decrease. |
Countries
Australia, Israel, New Zealand, Poland, Ukraine, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 22 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 95.5 months STANDARD_DEVIATION 25.01 |
| Bone Age (BA) | 6.542 years STANDARD_DEVIATION 2.4882 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 74 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 104 | 0 / 18 | 0 / 22 | 0 / 22 | 0 / 20 |
| other Total, other adverse events | 22 / 104 | 14 / 18 | 21 / 22 | 20 / 22 | 17 / 20 |
| serious Total, serious adverse events | 1 / 104 | 1 / 18 | 1 / 22 | 0 / 22 | 1 / 20 |
Outcome results
None listed