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

Phase 2

Completed

• Conditions: Growth Hormone Deficiency
• Interventions: Drug: rhGH Norditropin® pen (34 µg/kg); Drug: LUM-201

• Registration Number: NCT04614337
• Lead Sponsor: Lumos Pharma

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.

Study Timeline

• Study First Submitted: 2020-10-26
• Study First Submitted QC: 2020-11-02
• Study First Posted: 2020-11-04
• Study Start: 2020-12-31
• Primary Completion: 2024-09-04
• Study Completion: 2024-09-04
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rhGH (34 µg/kg/day)	rhGH Norditropin® pen (34 µg/kg)	-
LUM-201 (0.8 mg/kg/day)	LUM-201	-
LUM-201 (3.2 mg/kg/day)	LUM-201	-
LUM-201 (1.6 mg/kg/day)	LUM-201	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (43)

Center of Excellence in Diabetes and Endocrinology; 🇺🇸 Sacramento, California, United States

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Pediatric Endocrine Associates; 🇺🇸 Greenwood Village, Colorado, United States

Children's National Hospital; 🇺🇸 Washington, District of Columbia, United States

Atlanta Diabetes Associates; 🇺🇸 Atlanta, Georgia, United States

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

Novak Center For Childrens Health; 🇺🇸 Louisville, Kentucky, United States

UMass Memorial Medical Center; 🇺🇸 Worcester, Massachusetts, United States

M Health, Fairview Pediatric Specialty Clinics- Discovery Clinic; 🇺🇸 Minneapolis, Minnesota, United States

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