Clinical trial NCT05526066: Study for Adolescents and Adults With Ornithine Transcarbamylase Deficiency to Evaluate Safety and Tolerability of ARCT-810
Official title: Phase 2, Randomized, Double-Blind, Placebo-Controlled, Nested Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of ARCT-810 in Adolescent and Adult Participants With Ornithine Transcarbamylase Deficiency
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Ornithine Transcarbamylase Deficiency
OTC Deficiency
OTCD
Keywords: OTC
OTCD
Ornithine
Transcarbamylase
mRNA
Ornithine Transcarbamylase Deficiency
OTC Deficiency
Lead sponsor: Arcturus Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-09-02
Enrollment: 8
Sex: ALL
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: On Day 1, participants will receive a single dose of Study Drug via intravenous infusion.

If the safety observations are considered acceptable, that participant will enter the multiple-dose portion of the study in which they will receive a further 5 doses of Study Drug on Days 15, 29, 43, 57 and 71.
Primary purpose: TREATMENT

Brief summary: The primary objective is to evaluate the safety and tolerability of repeated doses of intravenously administered ARCT-810.

Detailed description: This study is a Phase 2, randomized, placebo-controlled study of ARCT-810 in people living with OTC deficiency 12 years of age and older. After an at least 4 week screening and diet stabilization period, participants will be randomized 3:1 to receive ARCT-810 or placebo. Following the first dose and safety evaluation, participants will receive up to an additional 5 doses of ARCT-810 or placebo, each separated by 14 days. The treatment period is followed by a 12-week observation period.

Eligibility criteria: Key Inclusion Criteria:

1. Adequate cognitive ability to understand study requirements and give informed consent
2. Males and females aged 12 to 65 years inclusive, at Screening
3. Documented diagnosis of OTC deficiency
4. Clinical stability (no clinical symptoms of hyperammonemia within 1 month, no hospitalizations for metabolic decompensation within 3 months, ≤ 2 hospitalizations within 1 year)
5. Stable protein-restricted diet, dietary supplements, and ammonia scavenger regimen (if applicable) for at least 28 days.
6. BMI = 18.0 - 32.0 kg/m2, inclusive for adults, and \>5th percentile for adolescents ≥12 to 17 years
7. Must be willing to adhere to contraception guidelines

Key Exclusion Criteria:

1. History of any OTC gene therapy, or history of liver-derived stem cell therapy in the past 3 years
2. History of other medical conditions that may make the participant unsuitable for inclusion or could interfere with study participation (e.g., uncontrolled hypertension or diabetes, malignancy, HIV, hepatitis B or C)
3. History of severe allergic reaction to liposomal or PEG-containing products
4. Abuse of illicit drugs, medications or alcohol
5. Clinically significant laboratory abnormalities on screening labs

Primary outcomes:
measure: Incidence, severity and dose-relationship of adverse events (AEs)
timeFrame: Week 23
Secondary outcomes:
measure: Plasma concentration area under the curve after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: Maximum observed plasma concentration (Cmax) after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: Time at which Cmax occurred after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: AUC0-inf after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: AUCExtrap after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: T1/2 after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: MRT0-inf after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: CL after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: Vss after first and last doses of ARCT-810
timeFrame: Up to 17 Weeks
measure: Urea Cycle Function
timeFrame: Week 12
measure: Plasma Ammonia
timeFrame: Week 11
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Marseille
country: France
facility: Hôpitaux Universitaires de Marseille - Hôpital de la Timone
city: Paris
country: France
facility: Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Rome
country: Italy
facility: IRCCS Ospedale Pediatrico Bambino Gesu
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) - Hospital Clínico Universitario
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset - Astrid Lindgrens Barnsjukhus
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital Birmingham
state: UK
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Foundation Trust
state: UK
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust - National Hospital for Neurology and Neurosurgery
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust - Salford Royal Hospital
Study officials:
References: