Congenital Muscular Dystrophy Ascending Multiple Dose Cohort Study Analyzing Pharmacokinetics at Three Dose Levels In Children and Adolescents With Assessment of Safety and Tolerability of Omigapil (CALLISTO)

NCT ID: NCT01805024

Last Updated: 2021-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2018-01-29

Brief Summary

The purpose of the study is to establish the pharmacokinetic profile of omigapil in paediatric and adolescent patients with CMD and to evaluate the safety and tolerability of omigapil.

Funding source - FDA OOPD

Conditions

Congenital Muscular Dystrophy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Omigapil

Omigapil treatment oral administration once per day after breakfast Cohort 1 Cohort 1 0.02 mg/kg/day Cohort 2 0.08 mg/kg/day Cohort 3a 0.04 mg/kg/day Cohort 3b 0.06 mg/kg/day

Group Type: EXPERIMENTAL

Omigapil

Intervention Type: DRUG

Cohort 1 0.02 mg/kg/day Cohort 2 0.08 mg/kg/day Cohort 3a 0.04 mg/kg/day Cohort 3b 0.06 mg/kg/day

Interventions

Omigapil

Cohort 1 0.02 mg/kg/day Cohort 2 0.08 mg/kg/day Cohort 3a 0.04 mg/kg/day Cohort 3b 0.06 mg/kg/day

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Ambulatory and non-ambulatory patients from age 5 - 16 years (5 years old and <17 years old) at time of screening with a clinical picture (see below) consistent with COL6-related dystrophy (COL6-RD) or LAMA2-related dystrophy (LAMA2-RD)
• Under regular review at a neuromuscular center
• On adequate double-barrier contraception (if of child-bearing potential)
• Stable on any allowed concomitant medications for 1 month prior to run in Phase
• Forced Vital Capacity (FVC) 30-80% of the predicted value and confirmed at Screening and Baseline visit(s)

For patients with Collagen VI-related dystrophy (COL6-RD)- required clinical picture:

• Muscle weakness: inability to walk or, if patient is still ambulatory, inability to run and > 5 s for 10 m walk

Genetic and Pathology:

• Molecular diagnosis of COL6-RD, defined by one dominant or two recessive mutation(s) in COL6A1, COL6A2 or COL6A3 known to cause the clinical picture,,

OR

• Histological diagnosis showing (i) absent or significantly decreased expression of collagen VI in muscle (overall reduction or basal lamina specific) or (ii) absent or significantly abnormal matrix in skin fibroblast culture

For patients with Laminin alpha 2 related dystrophy (LAMA2-RD) - required clinical picture:

• Muscle weakness: Inability to walk; if patient is still ambulatory, inability to run and > 5 s for 10 m walk.

Genetics and Pathology:

• Either: 2 identified pathologic or probable pathologic mutations in LAMA2 gene

OR:

• 1 identified pathologic or probable pathologic mutation in LAMA 2 gene with evidence of decrease in laminin alpha 2 staining on muscle or skin biopsy

OR:

• Evidence of decrease in laminin alpha 2 staining on muscle or skin biopsy with matching clinical phenotype and no suspicion of alpha dystroglycanopathy (aDG-RD) (clinically or by staining on muscle biopsy)

Exclusion Criteria

• Use of any investigational drug other than the study medication within 12 weeks of study start.
• Recurrent hospitalisation for chest infections in previous 2 years (≥2 per year)
• Patients with respiratory parameters (eg: low pulmonary function test value i.e. <30% or need for brief course of daytime non-invasive ventilation) currently affected by short term medications, or acute illness/ conditions (conduct baseline assessments when the patient has recovered and no longer taking acute medication)
• Any need for surgery (scoliosis, gastrostomy, other) in the preceding 24 weeks or foreseen during the course of the study.
• Patient has an intercurrent significant medical condition or situation which in the opinion of the Investigator or the study Medical Monitor may put the patient at significant risk, confound the study results or interfere significantly with the patient's participation in the study
• Failure to thrive, defined as:
• Falling 20 percentiles (20/100) in body weight in the 12 weeks preceding Screening/Baseline (based on family report of weight loss and acquiring relevant medical records)
• In patients below the 3rd percentile, any further drop in body weight percentile in the 12 weeks preceding Screening/Baseline (based on family report of weight loss and acquiring relevant medical records)
• Weight less than 17kg at Baseline
• Morbidly obese or grossly overweight (≥86 percentile BMI in children)
• History of epilepsy or on antiepileptic medication at Screening/Baseline
• Diabetes
• On daytime Non Invasive Ventilation (NIV)
• Intake of prohibited medication (as listed in Appendix I)
• Anticipated need for anesthesia during the course of this study
• Patients with renal impairment defined as urinary protein concentration ≥ 0.2 g/L
• Patients with moderate to severe hepatic impairment
• ALT ≥ 8x upper limit of normal (ULN) and total bilirubin 2x ULN (plus >35% 'direct' bilirubin), or
• ALT ≥ 8x ULN and INR >1.5 or ALT >2x baseline levels, and total bilirubin > 2x ULN (plus >35% 'direct' bilirubin), or
• ALT >2x baseline levels, and INR greater than 1.5,

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Santhera Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NINDS

Bethesda, Maryland, United States

Countries

United States

References

Foley AR, Yun P, Leach ME, Neuhaus SB, Averion GV, Hu Y, Hayes LH, Donkervoort S, Jain MS, Waite M, Parks R, Bharucha-Goebel DX, Mayer OH, Zou Y, Fink M, DeCoster J, Mendoza C, Arevalo C, Hausmann R, Petraki D, Cheung K, Bonnemann CG. Phase 1 Open-Label Study of Omigapil in Patients With LAMA2- or COL6-Related Dystrophy. Neurol Genet. 2024 May 29;10(3):e200148. doi: 10.1212/NXG.0000000000200148. eCollection 2024 Jun.

Reference Type: DERIVED

PMID: 38915423 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FDA-OPD 5076

Identifier Type: OTHER

Identifier Source: secondary_id

SNT-I-015

Identifier Type: -

Identifier Source: org_study_id

NCT02326831

Identifier Type: -

Identifier Source: nct_alias