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

Growth Hormone Deficiency Clinical Trial

— OraGrowtH210  

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04614337
• Other study ID #: LUM-201-01
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 31, 2020
• Est. completion date: October 2024

Study information

• Verified date: February 2024
• Source: Lumos Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 12 Years

Eligibility

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).

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Endocrine System Diseases
• Growth Hormone Deficiency

Intervention

Drug:
• LUM-201
Administered orally once daily
• rhGH Norditropin® pen (34 µg/kg)
Administered subcutaneously (s.c., under the skin) once daily.

Locations

Country	Name	City	State
Australia	Department of Pediatrics and Endocrinology- Monash Health	Clayton	Victoria
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	Royal Children's Hospital	Melbourne	Victoria
Australia	Queensland Children's Hospital	South Brisbane
Israel	Schneider Children's Medical Center Institute for Endocrinology and Diabetes National Center	Petah Tiqwa	Tiqwa
New Zealand	Liggins Institute, University of Auckland	Auckland
New Zealand	Wellington Regional Hospital CCDHB	Newtown	Wellington
Poland	Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdzialem Kardiologii, Uniwersytecki Dzieciecy Szpital Kliniczny im.Ludwika Zamenhofa w Bialymstoku	Bialystok
Poland	Klinika Endokrynologii i Chorob Metabolicznych, Instytut Centrum Zdrowia Matki Polki	Lodz
Poland	Klinika Pediatrii, Diabetologii i Endokrynologii Gdansk	Pomorskie
Poland	klinika Pediatrii, Endokrynologii i Diabetologii Dzieciecej	Rzeszów
Poland	Sonomed - Centrum Medyczne	Szczecin
Poland	Klinika Endokrynologii i Diabetologii, Instytut "Pomnik Centrum Zdrowia Dziecka	Warsaw
Poland	SP Dzieciecy Szpital Kliniczny w Warszawie	Warsaw
Poland	Klinika Endokrynologii i Diabetologii Wieku Rozwojowego UM	Wroclaw
Ukraine	State Institution 'V. P. Komissarenko Institute of Endocrinology and Metabolism of the National academy of medical science of Ukraine	Kyiv
United States	Texas Tech University Health Sciences Center	Amarillo	Texas
United States	Atlanta Diabetes Associates	Atlanta	Georgia
United States	UBMD Pediatrics	Buffalo	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia Health System	Charlottesville	Virginia
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Pediatric Endocrine Associates	Greenwood Village	Colorado
United States	Penn State College of Medicine	Hershey	Pennsylvania
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	University of Iowa	Iowa City	Iowa
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	Novak Center For Childrens Health	Louisville	Kentucky
United States	M Health, Fairview Pediatric Specialty Clinics- Discovery Clinic	Minneapolis	Minnesota
United States	The Mount Sinai Hospital	Mount Sinai	New York
United States	NYU Grossman School of Medicine	New York	New York
United States	University of Oklahoma Health Sciences Center, Pediatric Diabetes and Endocrinology	Oklahoma City	Oklahoma
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Center of Excellence in Diabetes and Endocrinology	Sacramento	California
United States	Children's Minnesota	Saint Paul	Minnesota
United States	Diabetes & Glandular Disease Clinic, P.A.	San Antonio	Texas
United States	Rady Children's Hospital	San Diego	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	MultiCare Institute for Research and Innovation	Tacoma	Washington
United States	Children's National Hospital	Washington	District of Columbia
United States	UMass Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Lumos Pharma

Countries where clinical trial is conducted

United States,  Australia,  Israel,  New Zealand,  Poland,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	AHV after 6 months on LUM-201 compared to rhGH	Annualized height velocity to be measured	Day 1 to Month 6
Secondary	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
Secondary	Incidence of adverse events in children with GHD	Number of events	Day 1 to Month 24
Secondary	Height standard deviation score (SDS)	Change in HT-SDS	Day 1 to Month 6 and Month 12
Secondary	Height velocity standard deviation score (HV-SDS)	Change in HV-SDS	Day 1 to Month 6, and Month 12
Secondary	Change in Weight	Change in Weight	Day 1 to Month 6, and Month 12
Secondary	Change in Weight SDS	Change in Weight-SDS	Day 1 to Month 6 and Month 12
Secondary	Change in BMI	Change in BMI	Day 1 to Month 6 and Month 12
Secondary	Change in BMI SDS	Change in BMI SDS	Day 1 to Month 6 and Month 12
Secondary	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
Secondary	Pharmacokinetics of LUM-201	Serum concentrations (Cmax/Steady State)	Day 1 to Month 6 and 12
Secondary	GH Concentration on maintenance treatment	Serum GH concentration	Day 1 to Month 6 and 12
Secondary	Insulin-like growth factor 1 SDS	Serum concentrations of insulin-like growth factor 1	Day 1 to Month 6 and 12