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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Growth Hormone Deficiency
• Intervention / Treatment: Drug: LUM-201; Drug: rhGH Norditropin® pen (34 µg/kg)

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 Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lumos Pharma; Phone Number: 515-598-2921; Email: clinical.trials@lumos-pharma.com

Study Locations

• Australia
  • South Brisbane, Australia
    • Queensland Children's Hospital
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2605
      • Canberra Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Department of Pediatrics and Endocrinology- Monash Health
    • Melbourne, Victoria, Australia, 3052
      • Royal Children's Hospital
• Israel
  • Tiqwa
    • Petah Tiqwa, Tiqwa, Israel, 4920235
      • Schneider Children's Medical Center Institute for Endocrinology and Diabetes National Center
• New Zealand
  • Auckland, New Zealand
    • Liggins Institute, University of Auckland
  • Wellington
    • Newtown, Wellington, New Zealand, 6021
      • Wellington Regional Hospital CCDHB
• Poland
  • Bialystok, Poland
    • Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdziałem Kardiologii, Uniwersytecki Dziecięcy Szpital Kliniczny im.Ludwika Zamenhofa w Białymstoku
  • Lodz, Poland
    • Klinika Endokrynologii i Chorob Metabolicznych, Instytut Centrum Zdrowia Matki Polki
  • Pomorskie, Poland
    • Klinika Pediatrii, Diabetologii i Endokrynologii Gdansk
  • Rzeszów, Poland
    • klinika Pediatrii, Endokrynologii i Diabetologii Dziecięcej
  • Szczecin, Poland
    • Sonomed - Centrum Medyczne
  • Warsaw, Poland
    • Klinika Endokrynologii i Diabetologii, Instytut "Pomnik Centrum Zdrowia Dziecka
  • Warsaw, Poland
    • SP Dziecięcy Szpital Kliniczny w Warszawie
  • Wrocław, Poland
    • Klinika Endokrynologii i Diabetologii Wieku Rozwojowego UM
• Ukraine
  • Kyiv, Ukraine, 04114
    • State Institution 'V. P. Komissarenko Institute of Endocrinology and Metabolism of the National academy of medical science of Ukraine
• United States
  • California
    • Sacramento, California, United States, 95821
      • Center Of Excellence in Diabetes and Endocrinology
    • San Diego, California, United States, 92123
      • Rady Children's Hospital
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • Pediatric Endocrine Associates
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Novak Center For Childrens Health
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
      • M Health, Fairview Pediatric Specialty Clinics- Discovery Clinic
    • Saint Paul, Minnesota, United States, 55102
      • Children's Minnesota
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • The Children's Mercy Hospital
  • New York
    • Buffalo, New York, United States, 14203
      • UBMD Pediatrics
    • Mount Sinai, New York, United States, 30093
      • The Mount Sinai Hospital
    • New York, New York, United States, 10016
      • NYU Grossman School of Medicine
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center, Pediatric Diabetes and Endocrinology
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • San Antonio, Texas, United States, 78229
      • Diabetes & Glandular Disease Clinic, P.A.
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital
    • Tacoma, Washington, United States, 98405
      • Multicare Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lumos Pharma

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2020
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: November 2, 2020
• First Posted (Actual): November 4, 2020

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 18, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Oral; Growth hormone secretagogue; GHD; Pediatric Growth Hormone Deficiency; Height; LUM-201; PEM; Catch-up growth; Predictive Enrichment Marker
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Pituitary Diseases; Dwarfism; Bone Diseases, Developmental; Hypopituitarism; Dwarfism, Pituitary; Endocrine System Diseases
• Other Study ID Numbers: LUM-201-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No