A Phase 1/2/3 Study of UX701 Gene Therapy in Adults with Wilson Disease”.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Ultragenyx Pharmaceutical Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Trial duration

13 Jun 2022 → ongoing

Decision date (initial)

2024-03-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Ultragenyx Pharmaceutical Inc.

External identifiers

EU CT number

2022-502873-40-00

EudraCT number

2020-005266-34

ClinicalTrials.gov

NCT04884815

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety, Pharmacodynamic, Dose response, Pharmacokinetic

Stage 1 (Phase 1/2) Primary:
- To evaluate the safety of single IV doses of UX701 in patients with Wilson disease
- To select the UX701 dose with the best benefit/risk profile based on the totality of safety and efficacy data at Week 52
Stage 2 (Phase 3) Primary
- To evaluate the effect of UX701 on copper regulation based on 24-hour urinary copper concentration and percent reduction in SOC medication at Week 52

Secondary objectives 1

1. Stage 2 (Phase 3) Secondary • To evaluate the effect of UX701 on biomarkers of copper metabolism and regulation • To evaluate the effect of UX701 on the need for continued SOC medication to regulate copper • To evaluate the effect of UX701 on patient-reported outcomes • To evaluate the effect of UX701 on liver function and health Stage 2 (Phase 3) Safety • To evaluate the safety of UX701

Conditions and MedDRA coding

Wilson disease

Study design 4 periods

Regulatory references

Scientific advice from competent authorities

Finnish Medicines Agency, Food And Drug Administration, Paul Ehrlich Institute, European Medicines Agency

Plan to share IPD

No

IPD plan description

Due to the rarity of Wilson Disease, individual patient data will not be shared in order to safeguard patient privacy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Individuals ≥ 18 years of age at the time of informed consent.
2. Confirmed diagnosis of Wilson disease based on genetic confirmation of heterozygous or homozygous biallelic ATP7B mutation.
3. Stable Wilson disease as evidenced by ongoing copper chelator (ie, penicillamine, trientine) and/or zinc therapy for at least 2 months at Screening, with no medication or dose changes for at least 2 months at Screening.
4. Ongoing restriction of high copper containing foods for at least 12 months at Screening and continued through study participation.
5. Willing and able to comply with all study procedures and requirements, including frequent blood collection, total urine collection over a 24-hour period, patient-reported outcome assessments, and longterm follow-up.

Exclusion criteria 1

1. 1.Detectable pre-existing antibodies to the AAV9 capsid (AAV9 DetectCDx). 2.Stage 1 only: History of copper chelator or zinc therapy noncompliance, in the Investigator’s judgment, within 6 months prior to Screening. 3.History of liver transplant. 4.Active decompensated hepatic cirrhosis or history of hepatic encephalopathy. 5.Significant hepatic inflammation as evidenced by any of the following laboratory abnormalities 6.Model for End-Stage Liver Disease (MELD) score > 13. 7.Hemoglobin < 9 g/dL. 8.Presence of Stage 3 or higher chronic kidney disease based on estimated glomerular filtration rate < 60 mL/min/1.73 m2. 9.Marked neurological deficit or compromise that, in the Investigator’s opinion, would interfere with the subject’s safety or ability to participate in the study. 10.Moderate to severe depression, recent or active suicidal ideation with intent or suicidal behavior, psychosis, or unstable psychiatric illness 20.Known hypersensitivity to UX701 or its excipients, copper chelators (ie, penicillamine, trientine), zinc, rituximab, tacrolimus, corticosteroids, or eculizumab that, in the Investigator’s judgment, places the subject at increased risk for adverse effects. 21.Participation in another gene transfer study or use of another gene transfer product before or during study participation. 24.Subjects with known hypersensitivity to amide-containing local anesthetics are excluded from participating in the optional liver biopsy substudy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Stage 1 (Phase 1/2) Primary Endpoints include the following assessments for UX701: Incidence of TEAEs, TESAEs, AESIs, treatment-related TEAEs, and treatment-related TESAEs
2. Stage 1 (Phase 1/2) Primary Endpoints include the following assessments for UX701: Change in 24-hour urinary copper concentration from Baseline at Week 52
3. Stage 1 (Phase 1/2) Primary Endpoints include the following assessments for UX701: Change in total copper, ceruloplasmin, NCC, free copper, and ceruloplasmin activity levels from Baseline at Week 52
4. Stage 1 (Phase 1/2) Primary Endpoints include the following assessments for UX701: Percent reduction in SOC medication by Week 52
5. Stage 1 (Phase 1/2) Primary Endpoints include the following assessments for UX701: Number of subjects who discontinue SOC medication by Week 52 (measured as complete response, response, or no response)
6. Stage 1 (Phase 1/2) Primary Endpoints include the following assessments for UX701: Number of consecutive weeks off SOC medication at Week 52
7. Stage 2 (Phase 3):Change in 24-hour urinary copper from Baseline at Week 52, evaluated for superiority
8. Stage 2 (Phase 3) Primary Endpoints;Percent reduction in SOC medication by Week 52, evaluated for superiority

Secondary endpoints 3

1. Stage 2 (Phase 3) Secondary Endpoints include the following comparisons between UX701 and placebo: Change in ceruloplasmin activity levels from Baseline at Week 52, evaluated for superiority
2. Stage 2 (Phase 3) Secondary Endpoints Number of subjects who discontinue SOC medication by Week 52
3. Stage 2 (Phase 3) Secondary Endpoints Change in FACIT-Fatigue scale score from Baseline at Week 52;Change in liver copper concentration assessed by liver biopsy from Baseline at Week 52

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Ultragenyx Pharmaceutical Inc.

Sponsor organisation

Ultragenyx Pharmaceutical Inc.

Address

60 Leveroni Court Suite 200

City

Novato

Postcode

94949-5746

Country

United States

Scientific contact point

Organisation

Ultragenyx Pharmaceutical Inc.

Contact name

Andrew Grimm

Public contact point

Organisation

Ultragenyx Pharmaceutical Inc.

Contact name

Ultragenyx trial information group

Third parties 21

Locations

5 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 83 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications