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

• ClinicalTrials.gov Identifier: NCT04614337
• Recruitment Status: Active, not recruiting
• First Posted: November 4, 2020
• Last Update Posted: February 20, 2024
• Sponsor: Lumos Pharma
• Information provided by (Responsible Party): Lumos Pharma

Tracking Information

• First Submitted Date: October 26, 2020
• First Posted Date: November 4, 2020
• Last Update Posted Date: February 20, 2024
• Actual Study Start Date: December 31, 2020
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 7, 2022)

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

Original Primary Outcome Measures (submitted: November 2, 2020)

Percentage of subjects selected by PEM strategy who meet target growth [ Time Frame: Day 1 to Month 6 ]

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

Current Secondary Outcome Measures (submitted: June 7, 2022)

• Degree of concordance between the first and second assessment with the PEM strategy. [ Time Frame: Screening to Day 1 ]
  Peak serum concentration of GH in response to a single provocative dose of LUM-201
• Incidence of adverse events in children with GHD [ Time Frame: Day 1 to Month 24 ]
  Number of events
• Height standard deviation score (SDS) [ Time Frame: Day 1 to Month 6 and Month 12 ]
  Change in HT-SDS
• Height velocity standard deviation score (HV-SDS) [ Time Frame: Day 1 to Month 6, and Month 12 ]
  Change in HV-SDS
• Change in Weight [ Time Frame: Day 1 to Month 6, and Month 12 ]
  Change in Weight
• Change in Weight SDS [ Time Frame: Day 1 to Month 6 and Month 12 ]
  Change in Weight-SDS
• Change in BMI [ Time Frame: Day 1 to Month 6 and Month 12 ]
  Change in BMI
• Change in BMI SDS [ Time Frame: Day 1 to Month 6 and Month 12 ]
  Change in BMI SDS
• Bone Age [ Time Frame: 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
• Pharmacokinetics of LUM-201 [ Time Frame: Day 1 to Month 6 and 12 ]
  Serum concentrations (Cmax/Steady State)
• GH Concentration on maintenance treatment [ Time Frame: Day 1 to Month 6 and 12 ]
  Serum GH concentration
• Insulin-like growth factor 1 SDS [ Time Frame: Day 1 to Month 6 and 12 ]
  Serum concentrations of insulin-like growth factor 1

Original Secondary Outcome Measures (submitted: November 2, 2020)

• Comparison of 6-month, AHVs achieved by daily rhGH and three dose levels of LUM-201 [ Time Frame: Day 1 to Month 6 ]
  6-month Annualized Height Velocity (AHV) measured as standing height with stadiometer
• Degree of concordance between the first and second assessment with the PEM strategy. [ Time Frame: Screening to Day 1 ]
  Peak serum concentration of GH in response to a single provocative dose of LUM-201
• Incidence of adverse events in children with GHD [ Time Frame: Day 1 to Month 6 ]
  Number of events
• Height standard deviation score (SDS) [ Time Frame: Day 1 to Month 6 ]
  Change in HT-SDS from Baseline to Month 6
• Change in Weight [ Time Frame: Day 1 to Month 6 ]
  Change in Weight from Baseline to Month 6
• Change in Weight SDS [ Time Frame: Day 1 to Month 6 ]
  Change in Weight-SDS from Baseline to Month 6
• Change in BMI [ Time Frame: Day 1 to Month 6 ]
  Change in BMI from Baseline to Month 6
• Change in BMI SDS [ Time Frame: Day 1 to Month 6 ]
  Change in BMI SDS from Baseline to Month 6
• Bone Age [ Time Frame: Day 1 to Month 6 ]
  Change in bone age, measured by X-ray of left hand and wrist using Greulich & Pyle atlas
• Pharmacokinetics of LUM-201 [ Time Frame: Day 1 to Month 6 ]
  Serum concentrations (Cmax/Steady State)
• GH Concentration on maintenance treatment [ Time Frame: Day 1 to Month 6 ]
  Serum GH concentration
• Insulin-like growth factor 1 [ Time Frame: Day 1 to Month 6 ]
  Serum concentrations of insulin-like growth factor 1

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Growth Hormone Deficiency

Intervention

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

Study Arms

• Experimental: LUM-201 (0.8 mg/kg/day)
  Intervention: Drug: LUM-201
• Experimental: LUM-201 (1.6 mg/kg/day)
  Intervention: Drug: LUM-201
• Experimental: LUM-201 (3.2 mg/kg/day)
  Intervention: Drug: LUM-201
• Active Comparator: rhGH (34 µg/kg/day)
  Intervention: Drug: rhGH Norditropin® pen (34 µg/kg)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: November 2, 2020): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 3 Years to 12 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Israel, New Zealand, Poland, Ukraine, United States
• Removed Location Countries: Russian Federation

Administrative Information

• NCT Number: NCT04614337
• Other Study ID Numbers: LUM-201-01
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Lumos Pharma
• Original Responsible Party: Same as current
• Current Study Sponsor: Lumos Pharma
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Lumos Pharma
• Verification Date: February 2024