Clinical trial NCT03403205: Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease
Official title: A Phase 3, Randomized, Rater-Blinded, Multi-Center Study to Evaluate the Efficacy and Safety of ALXN1840 Administered for 48 Weeks Versus Standard of Care in Patients With Wilson Disease Aged 12 Years and Older, With an Extension Period of up to 60 Months
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Wilson Disease
Keywords: Wilson Disease
ALXN1840
Copper
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-01-18
Enrollment: 214
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study will evaluate the efficacy and safety of ALXN1840 (formerly called WTX101) administered for 48 weeks compared to standard of care (SoC) in Wilson Disease (WD) participants aged 12 and older in the Primary Evaluation Period. In addition, efficacy and safety will be evaluated during an optional 60-month Extension Period.

Detailed description: The study consists of 2 cohorts. Cohort 1: Participants who have received SoC therapy for \> 28 days and Cohort 2: Participants who are treatment-naïve or who have received SoC therapy for ≤ 28 days.

All enrolled participants were randomized by cohort in a 2:1 ratio to treatment with ALXN1840 or SoC (either as continued therapy in Cohort 1 or as continued or initial therapy in Cohort 2).

Eligibility criteria: Key Inclusion Criteria:

* Established diagnosis of WD by Leipzig-Score ≥ 4
* Female participants of childbearing potential, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception starting at least 6 weeks before the Day 1 visit and continuing through 28 days after the last dose of either ALXN1840 or SoC
* Male participants, if heterosexually active, must be willing to follow protocol-specified guidance for highly effective contraception beginning at Day 1 visit and continuing through 90 days after last dose of either ALXN1840 or SoC

Key Exclusion Criteria:

* Decompensated hepatic cirrhosis
* MELD score \> 13
* Modified Nazer score \> 7
* Clinically significant gastrointestinal bleed within past 3 months
* Alanine aminotransferase \> 2 X upper limit of normal (ULN) for participants treated for \> 28 days with WD therapy (Cohort 1)
* Alanine aminotransferase \> 5 X ULN for treatment-naïve participants or participants who have been treated for ≤ 28 days (Cohort 2)
* Marked neurological disease requiring either nasogastric feeding or intensive inpatient medical care
* Hemoglobin \< 9 grams/deciliter
* History of seizure activity within 6 months prior to informed consent
* Pregnant (or women who are planning to become pregnant) or breastfeeding women
* Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus or seropositivity for human immunodeficiency virus (HIV)
* Previous treatment with tetrathiomolybdate
* Participants with end-stage renal disease on dialysis (chronic kidney disease stage 5) or creatinine clearance \< 30 milliliter/minute

Primary outcomes:
measure: Daily Mean Area Under The Effect-time Curve (AUEC) of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) From 0 to 48 Weeks (dNCC AUEC0-48W)
timeFrame: Baseline to Week 48
Secondary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Week 48
measure: Change From Baseline in the Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in UWDRS Part III Total Score at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in UWDRS Part III Functional Subscale Score at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in UWDRS Part III Individual Items/Subscales (Speech, Handwriting, Arising From a Chair, and Gait) Score at Week 48
timeFrame: Baseline, Week 48
measure: Clinical Global Impression-Improvement Scale (CGI-I) Score at Week 48
timeFrame: Week 48
measure: Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) Score at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Model for End-Stage Liver Disease (MELD) Score at Week 48
timeFrame: Baseline, Week 48
measure: Absolute Change From Baseline in Calculated Non-Ceruloplasmin Bound Copper (cNCC) or Calculated Non-Ceruloplasmin Bound Copper Corrected (cNCCcorrected) in Plasma at Week 48
timeFrame: Baseline, Week 48
measure: Percent Change From Baseline in cNCC or cNCCcorrected in Plasma at Week 48
timeFrame: Baseline, Week 48
measure: cNCC/cNCCcorrected Responder at Week 48
timeFrame: Week 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: New Haven
country: United States
facility: Research Site
state: Connecticut
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Houston
country: United States
facility: Research Site
state: Texas
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Adelaide
country: Australia
facility: Research Site
city: Concord
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Graz
country: Austria
facility: Research Site
city: Innsbruck
country: Austria
facility: Research Site
city: Vienna
country: Austria
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Praha 2
country: Czechia
facility: Research Site
city: Århus N
country: Denmark
facility: Research Site
city: Bron
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Hong Kong
country: Hong Kong
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat Gan
country: Israel
facility: Research Site
city: Chiba
country: Japan
facility: Research Site
city: Kumamoto-shi
country: Japan
facility: Research Site
city: Kurume-shi
country: Japan
facility: Research Site
city: Matsuyama-city
country: Japan
facility: Research Site
city: Meguro-ku
country: Japan
facility: Research Site
city: Sapporo-shi
country: Japan
facility: Research Site
city: Takatsuki-shi
country: Japan
facility: Research Site
city: Yokohama-shi
country: Japan
facility: Research Site
city: Daegu
country: Korea, Republic of
facility: Research Site
city: Grafton
country: New Zealand
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Moscow
country: Russian Federation
facility: Research Site
city: Nizhniy Novgorod
country: Russian Federation
facility: Research Site
city: St. Petersburg
country: Russian Federation
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Singapore
country: Singapore
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Sabadell
country: Spain
facility: Research Site
city: Taipei
country: Taiwan
facility: Research Site
city: Taoyuan City
country: Taiwan
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Izmir
country: Turkey
facility: Research Site
city: Edgbaston
country: United Kingdom
facility: Research Site
city: Guildford
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Alexion Pharmaceuticals, Inc.
name: Eugene S. Swenson, M.D., Ph.D.
role: STUDY_DIRECTOR
References: