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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05345171




Registration number
NCT05345171
Ethics application status
Date submitted
18/04/2022
Date registered
25/04/2022
Date last updated
3/05/2024

Titles & IDs
Public title
Clinical Study of DTX301 AAV- Mediated Gene Transfer for Ornithine Transcarbamylase(OTC) Deficiency
Scientific title
A Phase 3, Randomized, Double-blind, Placebo-controlled Study of Adeno-associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Human Ornithine Transcarbamylase (OTC) in Patients With Late-onset OTC Deficiency
Secondary ID [1] 0 0
2020-003384-25
Secondary ID [2] 0 0
DTX301-CL301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
OTC Deficiency 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Metabolic and Endocrine 0 0 0 0
Metabolic disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - DTX301
Other interventions - Placebo
Treatment: Drugs - Oral Corticosteroids
Treatment: Drugs - Placebo for oral corticosteroids
Treatment: Drugs - Sodium Acetate

Experimental: DTX301, Then Placebo - Participants receive single peripheral intravenous (IV) infusion of DTX301 in solution. At week 64, participants receive single peripheral IV infusion of placebo.

Experimental: Placebo, Then DTX301 - Participants receive single peripheral IV infusion of placebo. At week 64, participants receive single peripheral IV infusion of DTX301 in solution.


Other interventions: DTX301
non-replicating, self-complementary recombinant adeno-associated virus serotype 8 (AAV8) vector

Other interventions: Placebo
normal saline infusion

Treatment: Drugs: Oral Corticosteroids
Participants who receive DTX301 solution will receive oral corticosteroids.

Treatment: Drugs: Placebo for oral corticosteroids
Participants who receive Placebo will receive placebo corticosteroids to maintain the study blind

Treatment: Drugs: Sodium Acetate
A tracer for the Ureagenesis Rate Test (URT)
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Plasma Ammonia as Measured by 24-hour Ammonia (AUC0-24)
Timepoint [1] 0 0
Week 64
Primary outcome [2] 0 0
Percentage of Participants Who Have Achieved Complete Response
Timepoint [2] 0 0
Week 64
Secondary outcome [1] 0 0
Percentage of Participants Who Have Achieved Complete Response, Response, or No Response
Timepoint [1] 0 0
Week 64
Secondary outcome [2] 0 0
Patient Global Impression of Change (PGIC) Overall Change Score
Timepoint [2] 0 0
Week 64
Secondary outcome [3] 0 0
Rate of Hyperammonemic Crises (HACs) from Baseline to Week 64 Compared to Pre-Enrollment
Timepoint [3] 0 0
Pre-enrollment, Baseline, Week 64
Secondary outcome [4] 0 0
Change from Baseline in Plasma Ammonia (AUC0-24) After DTX301 Exposure
Timepoint [4] 0 0
Baseline, Up to Week 64
Secondary outcome [5] 0 0
Change from Baseline in Plasma Ammonia (AUC0-24)
Timepoint [5] 0 0
Baseline, Up to Week 64
Secondary outcome [6] 0 0
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs, Related Serious TEAEs and Adverse Events of Special Interest (AESIs)
Timepoint [6] 0 0
Up to Week 324
Secondary outcome [7] 0 0
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, Physical Examination Results, and Vital Sign Measurements
Timepoint [7] 0 0
Baseline, Up to Week 324
Secondary outcome [8] 0 0
Number of Participants With Anti-OTC Antibodies
Timepoint [8] 0 0
Up to Week 324

Eligibility
Key inclusion criteria
Key

- Confirmed clinical diagnosis of late-onset OTC deficiency with historical
documentation by enzymatic (ie, liver biopsy), biochemical (ie, hyperammonemia in the
presence of elevated plasma glutamine, low citrulline, and elevated spot urine orotic
acid), or molecular testing (ie, OTC analysis)

- Free from symptomatic hyperammonemia and has not required emergent active intervention
for hyperammonemia within 4 weeks before screening/baseline

- If on ongoing daily ammonia scavenger therapy, must be at stable daily dose(s) for = 4
weeks prior to screening

- If on a protein-restricted diet, must be on a stable total daily protein intake that
does not vary more than 20% for = 4 weeks prior to screening

- From the time written informed consent through Week 128, females of childbearing
potential and fertile males must consent to use highly effective contraception. If
female, agree not to become pregnant. If male, agree not father a child or donate
sperm

Key
Minimum age
12 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Significant hepatic inflammation or cirrhosis

- Estimated glomerular filtration rate < 60 mL/min/1.73 m2 at screening by the 2021
CKD-EPI creatinine-based formula (Inker et al., 2021) for patients = 18 years of age
or the Schwartz bedside formula (Schwartz and Work, 2009) for patients < 18 years of
age

- Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection,
documented by current use of antiviral therapy for HBV or HCV or by hepatitis B
surface antigen (HBsAg) or HCV RNA positivity

- Active infection (viral or bacterial)

- Detectable pre-existing antibodies to the AAV8 capsid

- Presence or history of any condition that, in the view of the Investigator, would
interfere with participation, pose undue risk, or would confound interpretation of
results

- Participation (current or previous) in another gene transfer study

Note: Additional inclusion/exclusion criteria may apply, per protocol

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/12/2028
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah
Country [9] 0 0
Argentina
State/province [9] 0 0
Buenos Aires
Country [10] 0 0
Argentina
State/province [10] 0 0
Córdoba
Country [11] 0 0
Brazil
State/province [11] 0 0
Porto Alegre
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
France
State/province [13] 0 0
Bron
Country [14] 0 0
France
State/province [14] 0 0
Paris
Country [15] 0 0
Germany
State/province [15] 0 0
Heidelberg
Country [16] 0 0
Italy
State/province [16] 0 0
Napoli
Country [17] 0 0
Italy
State/province [17] 0 0
Padova
Country [18] 0 0
Italy
State/province [18] 0 0
Torino
Country [19] 0 0
Japan
State/province [19] 0 0
Kumamoto
Country [20] 0 0
Japan
State/province [20] 0 0
Toyoake
Country [21] 0 0
Netherlands
State/province [21] 0 0
Rotterdam
Country [22] 0 0
Portugal
State/province [22] 0 0
Porto
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Santiago De Compostela
Country [25] 0 0
United Kingdom
State/province [25] 0 0
Birmingham

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Ultragenyx Pharmaceutical Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective is to evaluate the efficacy of DTX301 on the improvement of ornithine
transcarbamylase (OTC) function by maintaining safe plasma ammonia levels with removal of
dietary protein restriction and alternative pathway medication.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05345171
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Ultragenyx Pharmaceutical Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patients Contact: Trial Recruitment
Address 0 0
Country 0 0
Phone 0 0
1-888-756-8657
Fax 0 0
Email 0 0
TrialRecruitment@ultragenyx.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05345171