Growth hormone deficiency MedDRA version: 20.0 Level: PT Classification code 10056438 Term: Growth hormone deficiency System Organ Class: 10014698 - Endocrine disorders
Conditions
Sponsors
Lumos Pharma, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have an established diagnosis of idiopathic PGHD made prior to screening for entry into this study. This diagnosis is to be made in standard of care fashion incorporating biochemical, radiographic and auxological data. Specific inclusion criteria listed in this section for inclusion into this study protocol which are also used to diagnose PGHD in general are not intended to replace, supplant, or be an all-inclusive substitute for a standard of care diagnosis. Eligible subjects must be naïve-to-treatment and be prepubertal. 2. The diagnostic workup must include a maximal GH response -2.0 after consultation with the MMs. The use of National Growth Charts to compute HT-SDS is permitted for ex-US sites. 7. Have a baseline height velocity = 5.5 cm/year based on at least 6-months of growth. 8. Have a BA examination at Screening or within the 9 months prior to Screening that is delayed by = 6 months with respect to chronological age. BA should be based on the apparent BA of the proximal and distal phalanges, as opposed to the metacarpals, carpals and distal forearm. A central BA reader will make the final determination on BA eligibility. 9. Have prepubertal status as evidenced by Tanner Stage I breast development in girls and testicular volume 96.5%. 11. In girls, have genetic testing results to rule out Turner syndrome. If SHOX genetic testing results are available, they need to be negative. 12. Have normal thyroid function. Subjects diagnosed with hypothyroidism must have documented successful treatment for at least 30 days prior to Day 1. 13. Baseline IGF-1 concentration > 30 ng/mL (> 3.92 nmol/L) and a peak GH response of = 5 ng/mL from the Screening LUM-201 stimulation PEM test. 14. Subjects who are sexually active must use an acceptable form of contraception. Are the trial subjects under 18? yes Number of subjects for this age range: 80 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. 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 exogenous growth factor treatment. (Examples: diabetes, idiopathic short stature (ISS), SHOX-deficiency, any chondrodysplasia, constitutional growth delay, SGA, other named syndromes). 2. 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. 3. 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). 4. The presence of any circumstance likely to prevent successful completion of this trial. 5. Evidence or history of an intracranial mass (e.g., pituitary tumor, craniopharyngioma). 6. Prior treatment with growth factors including, but not limited to, GH, IGF-1, and GH secretagogues. (These may be used for limited times as a diagnostic test). 7. 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, or a diagnosis of organic PGHD. Note: if a maximal stimulated GH response is > 3 ng/mL on one of the prior standard of care GH stimulation tests, subject is potentially eligible for participation in the study. 8. Malnutrition as evidenced by medical history or a BMI 95th percentile. 10. Gestational age-adjusted birth weight < 3rd percentile (small for gestational age). 11. Participation in any therapeutic trial of investigational drug(s) within the prior 6 months. 12. Known or suspected allergy to LUM-201, rhGH or one of their excipients. 13. Unwilling to accept randomization assignment. 14. Treatment with medications known to be moderate or strong inhibitors or strong inducers of CYP3A/4. 15. Treatment with medications known to be predominantly metabolized (< 5% contribution by other isoforms) by either CYP3A/4, CYP2C8, CYP2C9 or CYP2C19. 16. Treatment 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). 17. History of spinal, cranial, or total body irradiation. 18. Recent commencement (within three months of the Screening visit) of non-stimulant therapy to treat attention deficit hyperactivity disorder (ADHD). MM should be contacted prior to screening of any potential subjects diagnosed with ADHD.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Preliminary clinical validation of predictive enrichment marker (PEM) strategy intended to select subjects likely to respond to therapy with LUM-201 based upon the percentage of subjects defined as PEM test positive (GH = 5 ng/mL and baseline insulin-like growth factor 1 [IGF-1] > 30 ng/mL [> 3.92 nmol/L]) who have a positive growth response (“responders”) defined as = 6.85 cm/yr annualized height velocity (AHV) from Baseline (Day 1) to Month 6.;Secondary Objective: Select a pediatric dose of LUM-201 for use in future studies including Phase 3 trial(s) based on comparison of 6-month, AHVs achieved by daily rhGH and the dose levels of LUM-201 treatment in subjects with pediatric growth hormone deficiency selected by predictive enrichment markers (PEMs) Assess the safety and tolerability of oral LUM-201 Assess the reproducibility of the PEM positive classification of subjects Assess additional clinical parameters of efficacy including change in height standard deviation score (HT-SDS) from Day 1 to Month 6, change in weight and weight SDS, change in body mass index and BMI SDS, change in Bone Age, change in predictive adult height Further explore pharmacokinetics of LUM-201 based upon plasma LUM-201 concentrations Determine short- and long-term pharmacodynamic (GH, IGF-1, IGFBP-3) responses to daily LUM-201 Characterize variance in AHVs of rhGH and LUM-201 to enable sample size estimates for future trials;Primary end point(s): Preliminary clinical validation of predictive enrichment marker (PEM) strategy intended to select subjects likely to respond to therapy with LUM-201 based upon the percentage of subjects defined as PEM test positive (GH = 5 ng/mL and IGF-1 > 30 ng/mL [> 3.92 nmol/L]) who have a positive growth response (“responders”) defined as = 6.85 cm/yr AHV from Baseline (Day 1) to Month 6.;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of reproducibility of the PEM positive classification. Selection of a pediatric dose of LUM-201 for use in future studies including Phase 3 trial(s) based on comparison of 6-month, AHVs achieved by daily rhGH and the dose levels of LUM-201 treatment in subjects with PGHD selected by PEMs.;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Australia, Israel, New Zealand, Poland, Russian Federation, Ukraine, United States
Contacts
Public ContactRegulatory Affairs, Lumos Pharma
Lumos Pharma
Outcome results
None listed