Clinical trial NCT04614337: Phase 2 Study of LUM-201 in Children With Growth Hormone Deficiency (OraGrowtH210 Trial)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Growth Hormone Deficiency
Keywords: GHD
Pediatric Growth Hormone Deficiency
LUM-201
Growth hormone secretagogue
Height
Catch-up growth
PEM
Oral
Predictive Enrichment Marker
Lead sponsor: Lumos Pharma
Sponsor class: INDUSTRY
First posted: 2020-11-04
Enrollment: 82
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Percentage of subjects selected by PEM strategy who meet target growth
timeFrame: Day 1 to Month 6
measure: AHV after 6 months on LUM-201 compared to rhGH
timeFrame: Day 1 to Month 6
Secondary outcomes:
measure: Degree of concordance between the first and second assessment with the PEM strategy.
timeFrame: Screening to Day 1
measure: Incidence of adverse events in children with GHD
timeFrame: Day 1 to Month 24
measure: Height standard deviation score (SDS)
timeFrame: Day 1 to Month 6 and Month 12
measure: Height velocity standard deviation score (HV-SDS)
timeFrame: Day 1 to Month 6, and Month 12
measure: Change in Weight
timeFrame: Day 1 to Month 6, and Month 12
measure: Change in Weight SDS
timeFrame: Day 1 to Month 6 and Month 12
measure: Change in BMI
timeFrame: Day 1 to Month 6 and Month 12
measure: Change in BMI SDS
timeFrame: Day 1 to Month 6 and Month 12
measure: Bone Age
timeFrame: Day 1 to Month 6 and Month 18
measure: Pharmacokinetics of LUM-201
timeFrame: Day 1 to Month 6 and 12
measure: GH Concentration on maintenance treatment
timeFrame: Day 1 to Month 6 and 12
measure: Insulin-like growth factor 1 SDS
timeFrame: Day 1 to Month 6 and 12
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: Center of Excellence in Diabetes and Endocrinology
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Greenwood Village
country: United States
facility: Pediatric Endocrine Associates
state: Colorado
city: Washington
country: United States
facility: Children's National Hospital
state: District of Columbia
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Louisville
country: United States
facility: Novak Center For Childrens Health
state: Kentucky
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Minneapolis
country: United States
facility: M Health, Fairview Pediatric Specialty Clinics- Discovery Clinic
state: Minnesota
city: Saint Paul
country: United States
facility: Children's Minnesota
state: Minnesota
city: Kansas City
country: United States
facility: The Children's Mercy Hospital
state: Missouri
city: Buffalo
country: United States
facility: UBMD Pediatrics
state: New York
city: Mount Sinai
country: United States
facility: The Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: NYU Grossman School of Medicine
state: New York
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center, Pediatric Diabetes and Endocrinology
state: Oklahoma
city: Hershey
country: United States
facility: Penn State College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Amarillo
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center
state: Texas
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Clinic, P.A.
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Tacoma
country: United States
facility: MultiCare Institute for Research and Innovation
state: Washington
city: Garran
country: Australia
facility: Canberra Hospital
state: Australian Capital Territory
city: Clayton
country: Australia
facility: Department of Pediatrics and Endocrinology- Monash Health
state: Victoria
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: South Brisbane
country: Australia
facility: Queensland Children's Hospital
city: Petah Tiqwa
country: Israel
facility: Schneider Children's Medical Center Institute for Endocrinology and Diabetes National Center
state: Tiqwa
city: Newtown
country: New Zealand
facility: Wellington Regional Hospital CCDHB
state: Wellington
city: Auckland
country: New Zealand
facility: Liggins Institute, University of Auckland
city: Bialystok
country: Poland
facility: Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdziałem Kardiologii, Uniwersytecki Dziecięcy Szpital Kliniczny im.Ludwika Zamenhofa w Białymstoku
city: Lodz
country: Poland
facility: Klinika Endokrynologii i Chorob Metabolicznych, Instytut Centrum Zdrowia Matki Polki
city: Pomorskie
country: Poland
facility: Klinika Pediatrii, Diabetologii i Endokrynologii Gdansk
city: Rzeszów
country: Poland
facility: klinika Pediatrii, Endokrynologii i Diabetologii Dziecięcej
city: Szczecin
country: Poland
facility: Sonomed - Centrum Medyczne
city: Warsaw
country: Poland
facility: Klinika Endokrynologii i Diabetologii, Instytut "Pomnik Centrum Zdrowia Dziecka
city: Warsaw
country: Poland
facility: SP Dziecięcy Szpital Kliniczny w Warszawie
city: Wrocław
country: Poland
facility: Klinika Endokrynologii i Diabetologii Wieku Rozwojowego UM
city: Kyiv
country: Ukraine
facility: State Institution 'V. P. Komissarenko Institute of Endocrinology and Metabolism of the National academy of medical science of Ukraine
Study officials:
References: