ArticleNeurology. Genetics2024
Phase 1 Open-Label Study of Omigapil in Patients With LAMA2- or COL6-Related Dystrophy.
Registry-linked trialAbstract read
In one paragraph
Article in Neurology. Genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01805024 (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), which is not on this map. Cited by 3 papers.
0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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)
Who cites it
3 citing papers in PubMed.
- Stress-induced nuclear GAPDH: Scientific update and clinical application.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Exon-Skipping Using Antisense Oligonucleotides for Laminin-Alpha2-Deficient Muscular Dystrophy.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Bioavailability as Proof to Authorize the Clinical Testing of Neurodegenerative Drugs-Protocols and Advice for the FDA to Meet the ALS Act Vision.International journal of molecular sciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
A Reghan FoleyFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0003-2168-1119
Pomi YunFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Meganne E LeachFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0009-0007-5599-3512
Sarah B NeuhausFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Gilberto V AverionFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0003-3454-0665
Ying HuFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0002-3602-0586
Leslie H HayesFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0002-0237-1978
Sandra DonkervoortFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0001-6399-1444
Minal S JainFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0003-4159-9876
Melissa WaiteFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Rebecca ParksFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0002-3331-727X
Diana X Bharucha-GoebelFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Oscar H MayerFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0003-3067-1545
Yaqun ZouFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0009-0006-4461-5471
Margaret FinkFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Jameice DeCosterFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Christopher MendozaFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Cynthia ArévaloFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Rudolf HausmannFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Diana PetrakiFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.
Ken CheungFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0001-8530-035X
Carsten G BönnemannFrom the Neuromuscular and Neurogenetics Disorders of Childhood Section (A.R.F., P.Y., M.E.L., S.B.N., G.V.A., Y.H., L.H.H., S.D., D.X.B.-G., Y.Z., M.F., J.D., C.M., C.A., C.G.B.), Neurogenetics Branch, NINDS, NIH, Bethesda, MD; Division of Neurology (M.E.L.), Oregon Health and Science University, Portland, OR; Department of Neurology (L.H.H.), Boston Children's Hospital, MA; Rehabilitation Medicine Department (M.S.J., M.W.); Occupational Therapy Section (R.P.), Rehabilitation Medicine Department, NIH, Bethesda, MD; Division of Neurology (D.X.B.-G.), Children's National Hospital, Washington, DC; Division of Pulmonology (O.M.), Children's Hospital of Philadelphia, PA; Santhera Pharmaceuticals (R.H., D.P.), Pratteln, Switzerland; and Department of Biostatistics (K.C.), Mailman School of Public Health, Columbia University, NY.ORCID https://orcid.org/0000-0002-5930-2324
Funding
Molecular and Clinical Manifestations of Matrix and Aggregate MyopathiesZIANS003129 · NINDS · NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE · PI BÖNNEMANN, CARSTEN · 2011 to 2025
$52.8MAbstract
Background and Objectives: Omigapil is a small molecule which inhibits the GAPDH-Siah1-mediated apoptosis pathway. Apoptosis is a pathomechanism underlying the congenital muscular dystrophy subtypes LAMA2-related dystrophy (LAMA2-RD) and COL6-related dystrophy (COL6-RD). Studies of omigapil in the (dy Methods: A phase 1 open-label, sequential group, ascending oral dose, cohort study of omigapil in patients with LAMA2-RD or COL6-RD ages 5-16 years was performed (1) to establish the pharmacokinetic (PK) profile of omigapil at a range of doses, (2) to evaluate the safety and tolerability of omigapil at a range of doses, and (3) to establish the feasibility of conducting disease-relevant clinical assessments. Patients were enrolled in cohorts of size 4, with each patient receiving 4 weeks of vehicle run-in and 12 weeks of study drug (at daily doses ranging from 0.02 to 0.08 mg/kg). PK data from each cohort were analyzed before each subsequent dosing cohort was enrolled. A novel, adaptive dose-finding method (stochastic approximation with virtual observation recursion) was used to allow for dose escalation/reduction between cohorts based on PK data. Results: Twenty patients were enrolled at the NIH (LAMA2-RD: N = 10; COL6-RD: N = 10). Slightly greater than dose-proportional increases in systemic exposure to omigapil were seen at doses 0.02-0.08 mg/kg/d. The dose which achieved patient exposure within the pre-established target area under the plasma concentration-vs-time curve (AUC Discussion: This study represents the thus far only clinical trial of a therapeutic small molecule for LAMA2-RD and COL6-RD, completed with an adaptive trial design to arrive at dose adjustments. The trial met its primary end point and established that the PK profile of omigapil is suitable for further development in pediatric patients with LAMA2-RD or COL6-RD, the most common forms of congenital muscular dystrophy. While within the short duration of the study disease-relevant clinical assessments did not demonstrate significant changes, this study establishes the feasibility of performing interventional clinical trials in these rare disease patient populations. Classification of Evidence: This study provides Class IV evidence of omigapil in a dose-finding phase 1 study. Trial Registration Information: Clinical Trials NCT01805024.
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NCT01805024ClinicalTrials.gov
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