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

Sponsor

Lumos Pharma (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04614337

Collaborator

(none)

Enrollment

Locations

Arms

Anticipated Duration (Months)

1.6

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Growth Hormone Deficiency	Drug: LUM-201 Drug: rhGH Norditropin® pen (34 µg/kg)	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Dec 31, 2020

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
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
Experimental: LUM-201 (3.2 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.

Outcome Measures

Primary Outcome Measures

Percentage of subjects selected by PEM strategy who meet target growth [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 [Day 1 to Month 6]
Annualized height velocity to be measured

Secondary Outcome Measures

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
Incidence of adverse events in children with GHD [Day 1 to Month 24]
Number of events
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 Weight [Day 1 to Month 6, and Month 12]
Change in Weight
Change in Weight SDS [Day 1 to Month 6 and Month 12]
Change in Weight-SDS
Change in BMI [Day 1 to Month 6 and Month 12]
Change in BMI
Change in BMI SDS [Day 1 to Month 6 and Month 12]
Change in BMI SDS
Bone Age [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 [Day 1 to Month 6 and 12]
Serum concentrations (Cmax/Steady State)
GH Concentration on maintenance treatment [Day 1 to Month 6 and 12]
Serum GH concentration
Insulin-like growth factor 1 SDS [Day 1 to Month 6 and 12]
Serum concentrations of insulin-like growth factor 1

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Center of Excellence in Diabetes and Endocrinology	Sacramento	California	United States	95821
2	Rady Children's Hospital	San Diego	California	United States	92123
3	Pediatric Endocrine Associates	Greenwood Village	Colorado	United States	80111
4	Children's National Hospital	Washington	District of Columbia	United States	20010
5	Orlando Health Inc.	Orlando	Florida	United States	32806
6	Atlanta Diabetes Associates	Atlanta	Georgia	United States	30318
7	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
8	University of Iowa	Iowa City	Iowa	United States	52242
9	Novak Center For Childrens Health	Louisville	Kentucky	United States	40202
10	Barry J Reiner, MD, LLC	Baltimore	Maryland	United States	21229
11	UMass Memorial Medical Center	Worcester	Massachusetts	United States	01655
12	M Health, Fairview Pediatric Specialty Clinics- Discovery Clinic	Minneapolis	Minnesota	United States	55454
13	Children's Minnesota	Saint Paul	Minnesota	United States	55102
14	The Children's Mercy Hospital	Kansas City	Missouri	United States	64111
15	Goryeb Children's Hospital	Morristown	New Jersey	United States	07962
16	UBMD Pediatrics	Buffalo	New York	United States	14203
17	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
18	University of Oklahoma Health Sciences Center, Pediatric Diabetes and Endocrinology	Oklahoma City	Oklahoma	United States	73104
19	Penn State College of Medicine	Hershey	Pennsylvania	United States	17033
20	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
21	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
22	Medical University of South Carolina	Charleston	South Carolina	United States	29425
23	Texas Tech University Health Sciences Center	Amarillo	Texas	United States	79106
24	Diabetes & Glandular Disease Clinic, P.A.	San Antonio	Texas	United States	78229
25	University of Virginia Health System	Charlottesville	Virginia	United States	22908
26	Seattle Children's Hospital	Seattle	Washington	United States	98105
27	MultiCare Institute for Research and Innovation	Tacoma	Washington	United States	98405
28	Canberra Hospital	Garran	Australian Capital Territory	Australia	2605
29	Department of Pediatrics and Endocrinology- Monash Health	Clayton	Victoria	Australia	3168
30	Royal Children's Hospital	Melbourne	Victoria	Australia	3052
31	Queensland Children's Hospital	South Brisbane		Australia
32	Schneider Children's Medical Center Institute for Endocrinology and Diabetes National Center	Petah Tiqwa	Tiqwa	Israel	4920235
33	Wellington Regional Hospital CCDHB	Newtown	Wellington	New Zealand	6021
34	Liggins Institute, University of Auckland	Auckland		New Zealand
35	Klinika Pediatrii, Endokrynologii, Diabetologii z Pododdziałem Kardiologii, Uniwersytecki Dziecięcy Szpital Kliniczny im.Ludwika Zamenhofa w Białymstoku	Bialystok		Poland
36	Klinika Endokrynologii i Chorob Metabolicznych, Instytut Centrum Zdrowia Matki Polki	Lodz		Poland
37	Klinika Pediatrii, Diabetologii i Endokrynologii Gdansk	Pomorskie		Poland
38	klinika Pediatrii, Endokrynologii i Diabetologii Dziecięcej	Rzeszów		Poland
39	Sonomed - Centrum Medyczne	Szczecin		Poland
40	Klinika Endokrynologii i Diabetologii, Instytut "Pomnik Centrum Zdrowia Dziecka	Warsaw		Poland
41	SP Dziecięcy Szpital Kliniczny w Warszawie	Warsaw		Poland
42	Klinika Endokrynologii i Diabetologii Wieku Rozwojowego UM	Wrocław		Poland
43	National Medical Research Center for Endocrinology of the Ministry of Healthcare of the Russian Federation	Moscow	Moscow Region	Russian Federation	117036
44	Bashkir State Medical University of the MoH of the Russian Federation; Clinic of BSMU	UFA	The Republic Of Bashkortostan	Russian Federation	450083
45	Republician Children's Clinical Hospital of the MoH of the Udmurt Republic	Izhevsk	Udmurt Republic	Russian Federation	426009
46	St. Petersburg State Pediatric Medical University of the MoH of the Russian Federation (Consultative and diagnostic center)	Saint Petersburg		Russian Federation	194100
47	Siberian State Medical University of the Ministry of Healthcare of the Russian Federation	Tomsk		Russian Federation	634050
48	State Institution 'V. P. Komissarenko Institute of Endocrinology and Metabolism of the National academy of medical science of Ukraine	Kyiv		Ukraine	04114
49	Regional Children Clinical Hospital' of Odesa Regional Council	Odesa		Ukraine	65013