There are no drug treatments for individuals with Congenital Contractures of the Limb and Face, Hypotonia, and Developmental Delay (CLIFAHDD), an ultra-rare and severe neurodevelopmental disease. The investigators have learned more about the cause of the disease and researched possible treatments based on both the cause of the disease and the way certain drugs work. The investigators are interested in understanding the safety of using aprepitant (a drug already approved by the United States Food \& Drug Administration \[FDA\] to treat nausea and vomiting for kids and adults who are receiving chemotherapy) on people diagnosed with CLIFAHDD. The overall goal of this Phase 1 study is to study whether this drug is safe for daily use in individuals with CLIFAHDD and to find more information on how it impacts daily functioning and quality of life. The total study will take around 8 months total. This includes the 90 days before the drug starts and the 21 days after the drug ends.
Diagnosis of CLIFAHDD (confirmed by clinical and genetic report per best practices)
NALCN variant with predicted NALCN gain-of-function in established functional assays and/or computational assessments
Age >6 months at the time of initial consent/assent
Weight >6kg at the time of initial consent/assent
Known hypersensitivity to any component of the study treatment formulation(s)
Concomitant use of pimozide, terfenadine, astemizole, cisapride, flibanserin, lomitapide (contraindicated CYP3A4 substrate)
Concomitant use of strong (Clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) or moderate (amiodarone, erythromycin, fluconazole, miconazole, diltiazem, verapamil, delavirdine, amprenavir, fosamprenavir, conivaptan, danazol, ketoconazole) CYP3A4 inhibitors and strong CYP3A4 inducers (apalutamide, carbamazepine, dexamethasone, enzalutamide, fosphenytoin, lumacaftor, midostaurin, mitotane, pentobarbital, phenobarbital, rifampin, phenytoin) or CYP3A4 substrates (Docetaxel, paclitaxel, etoposide, irinotecan, ifosfamide, imatinib, vinorelbine, vinblastine, vincristine, colchicine, axitinib). Participants on one of these medications but unable to discontinue for the trial and considered otherwise low risk should be discussed with the Independent Safety Monitor but may be considered for enrollment.
Concomitant use of high-risk cytochrome P450 family 2 subfamily C member 9 (CYP2C9) substrates (e.g., warfarin or phenytoin or tolbutamide)
Single group
Aprepitant Powder for Oral Suspension
DrugAdministration will begin at 1mg/kg up to a maximum of 40mg in weeks 1-4, then escalate to 2mg/kg up to a maximum of 80mg in weeks 5-8, then 3mg/kg up to a maximum of 125mg in weeks 9-12
Number of Adverse events
Adverse events will be assessed for relatedness to the study drug and assessed according to Common Terminology Criteria for Adverse Events (CTCAE) grade
Dose-limiting toxicity (DLT)
Number of events that lead to specified worsening of patients neurologic or non-neurologic condition during the treatment period which may lead to study treatment interruption for more than 14 days
Maximum administered dose
The highest dose at which no more than one instance of DLT is observed, or the maximum labeled dose
Area under the concentration-time curve (AUC)
The area under the concentration vs. time curve is a useful description of exposure of drug following administration. Following the initial dose, each participant's biological and pharmacokinetic response will be evaluated over a 72-hour period over a single dosing interval.
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The University of Texas Health Science Center at San Antonio
Lead sponsor
Channeling Hope Foundation
Collaborator
Cures Within Reach
Collaborator
