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

Phase 2
Completed
Conditions
Growth Hormone Deficiency
Interventions
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.

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.
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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).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
LUM-201 (1.6 mg/kg/day)LUM-201-
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-
Primary Outcome Measures
NameTimeMethod
AHV after 6 months on LUM-201 compared to rhGHDay 1 to Month 6

Annualized height velocity to be measured

Percentage of subjects selected by PEM strategy who meet target growthDay 1 to Month 6

Annualized height velocity (AHV) measured as standing height with stadiometer

Secondary Outcome Measures
NameTimeMethod
Incidence of adverse events in children with GHDDay 1 to Month 24

Number of events

Bone AgeDay 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 WeightDay 1 to Month 6, and Month 12

Change in Weight

Insulin-like growth factor 1 SDSDay 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 SDSDay 1 to Month 6 and Month 12

Change in Weight-SDS

Change in BMIDay 1 to Month 6 and Month 12

Change in BMI

Change in BMI SDSDay 1 to Month 6 and Month 12

Change in BMI SDS

GH Concentration on maintenance treatmentDay 1 to Month 6 and 12

Serum GH concentration

Pharmacokinetics of LUM-201Day 1 to Month 6 and 12

Serum concentrations (Cmax/Steady State)

Trial Locations

Locations (43)

The Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Atlanta Diabetes Associates

🇺🇸

Atlanta, Georgia, United States

Children's National Hospital

🇺🇸

Washington, District of Columbia, United States

Nationwide Children's Hospital

🇺🇸

Columbus, Ohio, United States

Children's Minnesota

🇺🇸

Saint Paul, Minnesota, United States

Pediatric Endocrine Associates

🇺🇸

Greenwood Village, Colorado, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

The Mount Sinai Hospital

🇺🇸

Mount Sinai, New York, United States

UBMD Pediatrics

🇺🇸

Buffalo, New York, United States

NYU Grossman School of Medicine

🇺🇸

New York, New York, United States

Penn State College of Medicine

🇺🇸

Hershey, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

Texas Tech University Health Sciences Center

🇺🇸

Amarillo, Texas, United States

Cook Children's Medical Center

🇺🇸

Fort Worth, Texas, United States

MultiCare Institute for Research and Innovation

🇺🇸

Tacoma, Washington, United States

University of Virginia Health System

🇺🇸

Charlottesville, Virginia, United States

Canberra Hospital

🇦🇺

Garran, Australian Capital Territory, Australia

Department of Pediatrics and Endocrinology- Monash Health

🇦🇺

Clayton, Victoria, Australia

Royal Children's Hospital

🇦🇺

Melbourne, Victoria, Australia

Schneider Children's Medical Center Institute for Endocrinology and Diabetes National Center

🇮🇱

Petah Tiqwa, Tiqwa, Israel

Liggins Institute, University of Auckland

🇳🇿

Auckland, New Zealand

Queensland Children's Hospital

🇦🇺

South Brisbane, Australia

Wellington Regional Hospital CCDHB

🇳🇿

Newtown, Wellington, New Zealand

Klinika Endokrynologii i Chorob Metabolicznych, Instytut Centrum Zdrowia Matki Polki

🇵🇱

Lodz, Poland

Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdziałem Kardiologii, Uniwersytecki Dziecięcy Szpital Kliniczny im.Ludwika Zamenhofa w Białymstoku

🇵🇱

Bialystok, Poland

Klinika Pediatrii, Diabetologii i Endokrynologii Gdansk

🇵🇱

Pomorskie, Poland

Klinika Endokrynologii i Diabetologii, Instytut "Pomnik Centrum Zdrowia Dziecka

🇵🇱

Warsaw, Poland

klinika Pediatrii, Endokrynologii i Diabetologii Dziecięcej

🇵🇱

Rzeszów, Poland

Sonomed - Centrum Medyczne

🇵🇱

Szczecin, Poland

SP Dziecięcy Szpital Kliniczny w Warszawie

🇵🇱

Warsaw, Poland

Klinika Endokrynologii i Diabetologii Wieku Rozwojowego UM

🇵🇱

Wrocław, Poland

State Institution 'V. P. Komissarenko Institute of Endocrinology and Metabolism of the National academy of medical science of Ukraine

🇺🇦

Kyiv, Ukraine

UMass Memorial Medical Center

🇺🇸

Worcester, Massachusetts, United States

Indiana University School of Medicine

🇺🇸

Indianapolis, Indiana, United States

Center of Excellence in Diabetes and Endocrinology

🇺🇸

Sacramento, California, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Diabetes & Glandular Disease Clinic, P.A.

🇺🇸

San Antonio, Texas, United States

Rady Children's Hospital

🇺🇸

San Diego, California, United States

Novak Center For Childrens Health

🇺🇸

Louisville, Kentucky, United States

M Health, Fairview Pediatric Specialty Clinics- Discovery Clinic

🇺🇸

Minneapolis, Minnesota, United States

The Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

University of Oklahoma Health Sciences Center, Pediatric Diabetes and Endocrinology

🇺🇸

Oklahoma City, Oklahoma, United States

Seattle Children's Hospital

🇺🇸

Seattle, Washington, United States

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