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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) (CALLISTO)

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ClinicalTrials.gov Identifier: NCT01805024
Recruitment Status : Completed
First Posted : March 5, 2013
Results First Posted : September 20, 2019
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE March 4, 2013
First Posted Date  ICMJE March 5, 2013
Results First Submitted Date  ICMJE April 3, 2019
Results First Posted Date  ICMJE September 20, 2019
Last Update Posted Date September 20, 2019
Study Start Date  ICMJE December 2014
Actual Primary Completion Date December 5, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 19, 2019)
  • Pharmacokinetic Profile of Omigapil:Maximum Observed Plasma Concentration (Cmax) of Omigapil [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 0 to 8 hours post-dose on Day 1, Week 4, Week 12 ]
Original Primary Outcome Measures  ICMJE
 (submitted: March 4, 2013)
Primary objective: to establish the pharmacokinetic profile of omigapil at a range of doses in paediatric and adolescent patients with CMD. [ Time Frame: Week 4 and Week 8 ]
Change History Complete list of historical versions of study NCT01805024 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 19, 2019)
Summary of All Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 12 weeks ]
TEAEs reported during the treatment period
Original Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2013)
Secondary objective: to evaluate the safety and tolerability of omigapil at a range of doses in paediatric and adolescent patients. [ Time Frame: Baseline, Week 4, 8 and 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: March 4, 2013)
Tertiary objective: to establish the feasibility of conducting disease-relevant clinical assessments in paediatric and adolescent patients with CMD to aid in the design of future studies [ Time Frame: Baseline, Week 12 and 16 ]
 
Descriptive Information
Brief Title  ICMJE 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)
Official Title  ICMJE 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)
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

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Congenital Muscular Dystrophy
Intervention  ICMJE Drug: 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
Study Arms  ICMJE Experimental: 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
Intervention: Drug: Omigapil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 13, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: March 4, 2013)
24
Actual Study Completion Date  ICMJE January 29, 2018
Actual Primary Completion Date December 5, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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,
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 5 Years to 16 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01805024
Other Study ID Numbers  ICMJE SNT-I-015
FDA-OPD 5076 ( Other Identifier: FDA )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Santhera Pharmaceuticals
Study Sponsor  ICMJE Santhera Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Santhera Pharmaceuticals
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP