Efficacy and Safety of ALXN1840 (Administered for 48 Weeks Versus Standard of Care in Participants With Wilson Disease

Sponsor

Alexion Pharmaceuticals (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03403205

Collaborator

(none)

215

Enrollment

Locations

Arms

96.4

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Wilson Disease	Drug: ALXN1840 Drug: SoC Therapy	Phase 3

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).

Study Design

Study Type:

Interventional

Actual Enrollment :

215 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Masking Description:

This study is rater-blinded for the Unified Wilson Disease Rating Scale (UWDRS) assessment only.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Feb 15, 2018

Actual Primary Completion Date :

Feb 24, 2021

Anticipated Study Completion Date :

Feb 28, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ALXN1840 ALXN1840 was administered orally for 48 weeks at doses ranging from 15 milligrams (mg) every other day (QOD) up to a titrated dose of 60 mg daily. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.	Drug: ALXN1840 ALXN1840 administered orally in 15 mg tablets Other Names: Formerly named WTX101 Tiomolibdic acid Tiomolibdate choline
Active Comparator: Standard of Care (SoC) Medication SoC medication was administered for 48 weeks. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.	Drug: SoC Therapy Depending on the site/region, participants randomized to receive SoC treatment will receive trientine, penicillamine, Zinc, or a combination of these medicines, administered according to standard regimens.

Arm

Intervention/Treatment

Experimental: ALXN1840

ALXN1840 was administered orally for 48 weeks at doses ranging from 15 milligrams (mg) every other day (QOD) up to a titrated dose of 60 mg daily. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.

Drug: ALXN1840

ALXN1840 administered orally in 15 mg tablets

Other Names:

Formerly named WTX101

Tiomolibdic acid

Tiomolibdate choline

Active Comparator: Standard of Care (SoC) Medication

SoC medication was administered for 48 weeks. Participants who completed the Primary Evaluation Period had the option to participate in the up to 60-month Extension Period.

Drug: SoC Therapy

Depending on the site/region, participants randomized to receive SoC treatment will receive trientine, penicillamine, Zinc, or a combination of these medicines, administered according to standard regimens.

Outcome Measures

Primary Outcome Measures

Daily Mean Area Under The Effect-time Curve (AUEC) Of Directly Measured Non-ceruloplasmin-bound Copper (dNCC) [Baseline to 48 weeks]

Secondary Outcome Measures

Change From Baseline In cNCC In Plasma. [Baseline, 48 weeks]
Number Of Participants With Treatment-emergent Adverse Events [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]
Effects of ALXN1840 on hepatic status [Baseline (Day 1) to 48 weeks]
Effects of ALXN1840 on disability status [Baseline (Day 1) to 48 weeks]
Effects of ALXN1840 on neurological status, as assessed by UWDRS Part III individual items/subscales (arising from a chair, gait, handwriting, and speech) [Baseline (Day 1) to 48 weeks]
Global effects of ALXN1840 on clinical symptoms as assessed by the Investigator on the Clinical Global Impression-Improvement Scale (CGI-I) and the Clinical Global Impression-Severity Scale (CGI-S) [Baseline (Day 1) to 48 weeks]
Effects of ALXN1840 on NCC responder rate [Baseline (Day 1) to 48 weeks]
Change From Baseline In The Unified Wilson Disease Rating Scale (UWDRS) Part II Total Score [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]
Change From Baseline In UWDRS Part III Total Score And Individual Items/Subscales (Arising From A Chair, Gait, Handwriting, And Speech) [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]
Clinical Global Impression-Improvement Scale (CGI-I) [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]
Change From Baseline In Clinical Global Impression Severity Scale (CGI-S) [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]
Change From Baseline In Model For End-Stage Liver Disease (MELD) Score [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]
Change From Baseline In Calculated NCC (cNCC) In Plasma [Baseline (Day 1), 48 weeks]
cNCC Responder Rate [Primary Evaluation Period: Baseline through 48 weeks; Extension Period: Baseline through up to 60 Months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Established diagnosis of WD by Leipzig-Score ≥ than 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA Neurological Services	Los Angeles	California	United States	90095
2	Yale University School of Medicine	New Haven	Connecticut	United States	06510
3	Northwestern University	Chicago	Illinois	United States	60611
4	University of Michigan	Ann Arbor	Michigan	United States	48109
5	St. Luke's Health Baylor College of Medicine Medical Center	Houston	Texas	United States	77030
6	Texas Children's Hospital (TCH) - Viral Hepatitis Clinic	Houston	Texas	United States	77030
7	Seattle Children's Hospital	Seattle	Washington	United States	98145
8	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
9	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2139
10	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
11	Medizinische Universitat Graz	Graz	Styria	Austria	8036
12	Medizinische Universitat Innsbruck	Innsbruck	Tyrol	Austria	6020
13	Medizinische Universitat Wien	Wien	Vienna	Austria	1090
14	University Health Network	Toronto	Ontario	Canada	M5G 2C4
15	Vseobecna Fakultni Nemocnice v Praze	Prague		Czechia	12808
16	Aarhus Universitetshospital	Aarhus		Denmark	8200
17	CHU Lyon- Hopital Femme- Mere-Enfant	Bron		France	69677
18	Hopital Lariboisiere	Paris		France	75010
19	Universittsklinikum Leipzig AR	Leipzig	Sachsen	Germany	04103
20	ifi-Studien und Projekte Gmbh	Hamburg		Germany	20099
21	University Hospital Heidelberg	Heidelberg		Germany	69120
22	Queen Mary Hospital	Hong Kong		Hong Kong	852
23	Semmelweis Egyetem	Budapest		Hungary	1085
24	Hadassah Ein-Karem Medical Center - Liver Unit	Jerusalem		Israel	9112001
25	Sheba Medical Center at Tel Hashomer	Tel-Hashomer		Israel	52621
26	Chiba Children's Hospital	Chiba-Shi	Chiba	Japan	266-0007
27	Ehime Prefectural Central Hospital	Matsuyama-Shi	Ehime	Japan	790-0024
28	Kurume University Hospital	Kurume-Shi	Fukuoka	Japan	830-0011
29	Hokkaido Medical Center	Sapporo-Shi	Hokkaido	Japan	063-0005
30	Saiseikai Yokohamashi Tobu Hospital	Yokohama-Shi	Kanagawa	Japan	230-8765
31	Osaka Medical College Hospital	Takatsuki-Shi	Osaka	Japan	569-8686
32	Toho University Ohashi Medical Center	Meguro-Ku	Tokyo	Japan	153-8515
33	Kyungpook National University Children's Hospital	Daegu		Korea, Republic of	41944
34	Auckland Public Hospital	Auckland		New Zealand	1023
35	Instytut Pomnik Centrum Zdrowia Dziecka	Warszawa	Woj. Mazowieckie	Poland	04-730
36	Instytut Psychiatrii i Neurologii	Warszawa		Poland	02-957
37	National Scientific Institute of Nutrition	Moscow		Russian Federation	115446
38	Clinic of Rheumatology, Internal and Occupational Diseases	Moscow		Russian Federation	119435
39	First Moscow State Medical University n.a. I.M. Sechenov	Moscow		Russian Federation	119435
40	"Volga Research Medical University" of the Ministry of Health of Russia	Nizhny Novgorod		Russian Federation	603950
41	St. Petersburg Clinical Hospital of the Russian Academy of Sciences	Saint Petersburg		Russian Federation	194017
42	Clinical Centre of Serbia	Belgrade		Serbia	11000
43	Singapore General Hospital (SGH)	Singapore		Singapore	169608
44	Parc Tauli	Sabadell	Barcelona	Spain	08208
45	Hospital Clínic i Provincial de Barcelona	Barcelona		Spain	08036
46	Hospital Materno Infantil de Málaga	Málaga		Spain	29011
47	Chang Gung Memorial Hospital-Linkou Branch	Taoyuan City		Taiwan	333
48	Hacettepe Universitesi - Tip Fakultesi (Hacettepe University Faculty of Medicine)	Ankara		Turkey	06620
49	Koc University Medical Faculty	Istanbul		Turkey	34010
50	Istanbul Uni. Istanbul Medical Faculty Hospital	Istanbul		Turkey	34104
51	Ege University School of Medicine, Department of Gastroenterology	Izmir		Turkey	35100
52	Sandwell and West Birmingham Hospitals NHS Trust	Birmingham	England	United Kingdom	B15 2TH
53	Royal Surrey County Hospital NHS Foundation Trust	Guildford	England	United Kingdom	GU2 7XX
54	Kings College Hospital	London	England	United Kingdom	SE5 9RS

Sponsors and Collaborators

Alexion Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Alexion Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT03403205

Other Study ID Numbers:

WTX101-301

First Posted:

Jan 18, 2018

Last Update Posted:

May 9, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Alexion Pharmaceuticals

Wilson Disease

ALXN1840

Additional relevant MeSH terms:

Hepatolenticular Degeneration

Choline

Study Results

No Results Posted as of May 9, 2022