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)

NCT01805024 | Completed Phase 1 Results

• 2 other identifiers: SNT-I-015FDA-OPD 5076
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic Profile of Omigapil:Maximum Observed Plasma Concentration (Cmax) of Omigapil

  0.5, 1, 1.5, 2, 4 and 8 hours post-dose on Day 1, Week 4 and Week 12

• Pharmacokinetic Profile of Omigapil: Time at Which Cmax Was Apparent (Tmax) of Omigapil

  0.5, 1, 1.5, 2, 4 and 8 hours post-dose on Day 1, Week 4 and Week 12

• Pharmacokinetic Profile of Omigapil Area Under the Plasma Concentration Versus Time Curve From Time Zero to 8h Post-dose (AUC0-8)

  0 to 8 hours post-dose on Day 1, Week 4, Week 12

Secondary Outcomes (1)

• Summary of All Treatment-emergent Adverse Events (TEAEs)

  12 weeks

Study Arms (1)

Omigapil

EXPERIMENTAL

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

Drug: Omigapil

Interventions

Omigapil 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

Omigapil

Eligibility Criteria

• Age: 5 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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,,
• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Santhera Pharmaceuticals: lead

Study Sites (1)

NINDS

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• 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.

  PMID: 38915423 DERIVED

MeSH Terms

Interventions

dibenzo(b,f)oxepin-10-ylmethyl-methyl-prop-2-ynyl-amine

Results Point of Contact

• Title: Roxana Drake
• Organization: Santhera Pharmaceuticals

roxana.drake@santhera.com

+41 61 906 89 29

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2013
• First Posted: March 5, 2013
• Study Start: December 1, 2014
• Primary Completion: December 5, 2017
• Study Completion: January 29, 2018
• Last Updated: September 24, 2021
• Results First Posted: September 20, 2019

Record last verified: 2021-09

Locations

US (1)