Aprepitant for the Treatment of CLIFAHDD

NCT07845825 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: STUDY00002877
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CLIFAHDD; NALCN Channelopathy; Ataxia - Other; Congenital Contractures of the Limbs and Face, Hypotonia, and Developmental Delay; Neurodevelopmental Disorder (Diagnosis)

Keywords

CLIFAHDD; Sodium leak ion channel; NALCN; Congenital Contractures of the Limb and Face, Hypotonia, and Developmental Delay; Aprepitant; Channelopathy; Neurodevelopmental Disorder; Neurogenetic Disorder; Ataxia

Outcome Measures

Primary Outcomes (3)

• 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

  Baseline to 24 weeks

• 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

  Baseline to 24 weeks

• Maximum administered dose

  The highest dose at which no more than one instance of DLT is observed, or the maximum labeled dose

  Baseline to 24 weeks

Secondary Outcomes (1)

• Area under the concentration-time curve (AUC)

  Dose time to 72 hours

Study Arms (1)

Aprepitant treatment group

EXPERIMENTAL

Participant enrolled in the study will be administered oral aprepitant to evaluate safety and tolerability

Drug: Aprepitant Powder for Oral Suspension

Interventions

Aprepitant Powder for Oral Suspension DRUG

Administration 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

Also known as: Emend

Aprepitant treatment group

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Ability of participant or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.
• For children (\<18y at time of consent/assent), informed assent (if developmentally appropriate) and parental informed consent to participate in the study
• Willingness to comply with all study-related requirements, including Aprepitant regimen and travel to San Antonio, TX for specified visits
• Has adequate organ functions as defined by the following laboratory parameters at baseline (laboratory parameters outside of these ranges that are deemed clinically insignificant should be discussed with the Independent Safety Monitor):
• Absolute neutrophil count ≥1000 cells/uL;
• hemoglobin ≥8.5 g/dL;
• platelet count ≥100,000/mm3;
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN);
• total bilirubin ≤ 1.5 x institutional ULN (exception: subjects with known Gilbert's syndrome and total bilirubin ≤2 x institutional ULN at screening or anytime during the prior 6 months are eligible);
• adequate renal function defined as calculated creatinine clearance \>60 mL/min using the Cockcroft Gault Method;
• acceptable coagulation parameters including international normalized ratio (INR) \<1.4 and partial thromboplastin time (PTT) ≤ 1.5 x institutional ULN;

You may not qualify if:

• 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)
• Patients who are medically unstable or have been hospitalized for an acute medical condition in the 3 months prior to the first active drug visit
• Patients who are acutely ill in the hospital or intensive care unit (ICU)
• Any other history of clinically significant acute or chronic neurologic disease, respiratory disease, cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, infectious disease, or any other medical or psychiatric condition that in the opinion of the investigator or study clinician will significantly increase the safety risk for the subject or confound the interpretation of the study data.
• Currently receiving any other investigational agents or has received study treatment or used an investigational device within 30 days of the first dose of treatment
• Caregivers unwilling to follow study procedures or follow protocol as outlined.
• Pregnancy

Sponsors & Collaborators

• Channeling Hope Foundation: collaborator
• Cures Within Reach: collaborator
• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

UT Health San Antonio - Center for Brain Health

San Antonio, Texas, 78229, United States

Location

Related Links

• Study sponsor and 501c3 patient advocacy group to advance care and develop treatments for NALCN Channel Related Diseases

MeSH Terms

Conditions

Facies; Muscle Hypotonia; Learning Disabilities; Neurodevelopmental Disorders; Disease; Channelopathies; Ataxia

Interventions

Suspensions; Aprepitant

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Communication Disorders; Neurobehavioral Manifestations; Mental Disorders; Dyskinesias

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Megan Iammarino, DPT

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Megan Iammarino, DPT

CONTACT

440-382-3366; iammarinom@uthscsa.edu

Randee Kent-Baron

CONTACT

210-450-0524; kentbaron@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single-center, one arm, open-label, dose-escalation clinical trial

Study Record Dates

• First Submitted: September 21, 2026
• First Posted: September 29, 2026
• Study Start: October 1, 2026
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): July 31, 2027
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF, CSR
• Time Frame: After study completion and data analysis and acceptance into a peer review journal.

Locations

US (1)