NIH Clinical Center Search the Studies: Study Number, Study Title

Protocol Details

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

This study is NOT currently recruiting participants.

Summary | Eligibility | Citations | Contacts

Summary

Number

15-N-0018

Sponsoring Institute

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Completed Study; data analyses ongoing
Gender: Male & Female
Min Age: 5
Max Age: 16

Referral Letter Required

No

Population Exclusion(s)

None

Special Instructions

Currently Not Provided

Keywords

Dystrophy

Recruitment Keyword(s)

None

Condition(s)

Dystrophy

Investigational Drug(s)

Omigapil powder for oral solution

Investigational Device(s)

None

Intervention(s)

Drug: Omigapil

Supporting Site

National Institute of Neurological Disorders and Stroke

Background:

- Congenital muscular dystrophy (CMD) affects muscles and breathing. Some people with CMD don t have enough muscle proteins like laminin alpha 2 (LAMA2) or collagen VI (COLVI). The new drug Omigapil may help these people.

Objectives:

- To see how children s bodies process the drug Omigapil. To evaluate tests for future Omigapil studies.

Eligibility:

- People 5 16 years old with LAMA2- or COLVI-related CMD

Design:

- Participants will be screened with medical history, physical exam, and heart, blood, and urine tests.

- Participants will have 6 7 study visits of 2 3 days each as outpatients.

- Screening tests will be repeated at every visit. Researchers will take pictures and videos of participants.

- Visit 1:

- Liver and muscle ultrasound.

- Muscle MRI. Participants will lie in a machine that takes pictures of muscles.

- Muscle tests: gripping, walking, and doing tasks.

- Lung tests: breathing into a machine.

- Participants will take a sweet syrup with no study drug daily for 4 weeks.

- Between visits, parents will test participants lung function with a device and keep a medicine diary. Study staff will call weekly to check in.

- Visit 2:

- Pharmacokinetic blood draws. A small tube (IV) is placed in a vein by needle. Blood is drawn 6 times over 8 hours.

- Participants will take a syrup containing the study drug every morning for 12 weeks.

- Visit 3:

- Pharmacokinetic blood draws.

- Visit 4:

- Lung and muscle tests.

- Visit 5:

- Visit 1 tests repeated.

- Pharmacokinetic blood draws.

- Participants will stop taking the study drug after this visit.

- Visit 6:

- Lung and muscle tests.

--Back to Top--

Eligibility

Inclusion Criteria:

The following criteria should be assessed during the Screening and Baseline Visit(s). If any does not apply, the patient must not be included in the study:

- Ambulatory and non-ambulatory patients from age 5 - 16 years (greater than or equal to 5 years old and <17 years old) at time of screening with a clinical picture (see below) consistent with LAMA2-RD or COL6-RD

-Under regular review at a neuromuscular centre

-On adequate double-barrier contraception (if of child-bearing potential)

-Stable on any allowed concomitant medications for 1 month prior to run in phase

For patients with 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)

-FVC 30 - 80% of the predicted value and confirmed at Screening and Baseline visit(s)

Genetic and Pathology:

-Molecular diagnosis of collagen VI related dystrophy, 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 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.

-FVC 30 - 80% of the predicted value and confirmed at Screening and Baseline visit(s)

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

The following criteria should be assessed during Screening and Baseline Visit(s). If any applies, the patient must not be included in the study:

-Use of any investigational drug other than the study medication within 12 weeks of study start.

-Recurrent hospitalization for chest infections in previous 2 years (greater than or equal to 2 per year)

-Patients with respiratory parameters (eg: low pulmonary function test value i.e. <30% predicted or need for 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 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 review of relevant medical records)

-Weight less than 17kg at Baseline

-Morbidly obese or grossly overweight (greater than or equal to 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

-Anticipated need for anesthesia during the course of this study

-Patients with renal impairment defined as urinary protein concentration greater than or equal to 0.2 g/L

-Patients with moderate to severe hepatic impairment:

-ALT greater than or equal to 8x ULN and total bilirubin 2x ULN (plus >35% direct bilirubin),

OR

-ALT greater than or equal to 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,

OR

-ALT greater than or equal to 8 x ULN and associated with symptoms of hepatitis (e.g. onset or worsening of nausea, anorexia, jaundice or abdominal pain) or hypersensitivity (e.g. fever, rash, eosinophilia),

OR

-GGT > 2-3x ULN and bilirubin 2x ULN (plus >35% direct bilirubin),

OR

-GGT >2-3x ULN and INR >1.5


--Back to Top--

Citations:

Not Provided

--Back to Top--

Contacts:

Principal Investigator

Referral Contact

For more information:

Carsten G. Bonnemann, M.D.
National Institute of Neurological Disorders and Stroke (NINDS)
BG 35 RM 2A116
35 CONVENT DR
BETHESDA MD 20814
(301) 594-5496
bonnemanncg@mail.nih.gov

Gilberto V. Averion
National Institute of Neurological Disorders and Stroke (NINDS)
National Institutes of Health
Building 10
Room 12N210
10 Center Drive
Bethesda, Maryland 20892
(301) 594-2760
gilbertoav@mail.nih.gov

Office of Patient Recruitment
National Institutes of Health Clinical Center (CC)
Building 61, 10 Cloister Court
Bethesda, Maryland 20892
Toll Free: 1-800-411-1222
Local Phone: 301-451-4383
TTY: 1-866-411-1010
PRPL@cc.nih.gov

Clinical Trials Number:

NCT01805024

--Back to Top--