ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of WTX101 Administered for 48 Weeks Versus Standard of Care in Wilson Disease Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03403205
Recruitment Status : Recruiting
First Posted : January 18, 2018
Last Update Posted : July 2, 2018
Sponsor:
Information provided by (Responsible Party):
Wilson Therapeutics AB

Brief Summary:
Wilson Disease (WD) is an autosomal recessive disorder of impaired copper (CU) transport caused by mutations in the ATP7B gene. WTX101 (bis-choline tetrathiomolybdate) is a first-in-class copper-protein-binding agent with a unique mechanism of action, under investigation as a novel therapy for WD. It is formulated as an enteric coated tablet (15 mg strength) for oral administration. The purpose of this study is to evaluate the efficacy of WTX101 administered for 48 weeks compared to standard of care (SOC) in WD subjects aged 18 and older.

Condition or disease Intervention/treatment Phase
Wilson Disease Drug: WTX101 Drug: SOC Therapy Phase 3

Detailed Description:

This study is a randomized, rater-blinded, multi-center study assessing the efficacy and safety of an individualized WTX101 dosing regimen administered for 48 weeks, compared to SoC, in WD subjects aged 18 and older. Approximately 100 subjects will be enrolled at approximately 5 to 10 North American sites and 15 to 25 sites in the rest of the world. Subjects who complete the 48-week treatment period will be offered to participate in an Extension Phase of the study to evaluate the long-term safety and durability of treatment effect of WTX101.

The primary objective is to evaluate the efficacy of WTX101 administered for 48 weeks, compared to SOC, on Cu control in WD subjects aged 18 and older. Copper control will be assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non-ceruloplasmin-bound copper (NCC) levels. For WTX101-treated subjects, the NCC level will be corrected for the amount of Cu bound to the WTX101 tripartite complex (TPC) (NCCcorrected).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 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. The rater will be blinded and will have no knowledge of the subject's treatment assignment and no access to systems that could result in potential unblinding of treatment assignment. Both raters and subjects will be instructed to avoid lines of inquiry, questions, and responses that could potentially lead to unblinding of the subject's treatment. The blinding will be documented by the rater after each UWDRS assessment. The rater assessments will be strictly limited to administration of the protocol specified instruments and assessments.
Primary Purpose: Treatment
Official Title: A Phase 3, Randomised, Rater-Blinded, Multi-Centre Study to Evaluate the Efficacy and Safety of WTX101 Administered for 48 Weeks Versus Standard of Care in Wilson Disease Subjects Aged 18 and Older With an Extension Phase of up to 60 Months
Actual Study Start Date : February 15, 2018
Estimated Primary Completion Date : December 18, 2019
Estimated Study Completion Date : February 14, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Wilson Disease

Arm Intervention/treatment
Experimental: 15-60 mg WTX101 to subjects treated >28 days with SOC
Subjects treated for >28 days with chelation or zinc (Zn) therapy or a combination of both chelation and Zn therapy will be treated with 15 mg every other day (QOD) to 60 mg once daily (QD) of WTX101 by oral administration.
Drug: WTX101
WTX101 administered orally in 15 mg tablets

Active Comparator: SOC for subjects treated with SOC >28 days prior
Subjects treated for >28 days with chelation or Zn therapy or a combination of both chelation and Zn therapy will continue to receive the SOC therapy.
Drug: SOC Therapy
Subjects randomized to receive SOC treatment will continue their current therapy or initiate therapy with chelation, Zn, or a combination of both chelation and Zn therapy. Depending on the site/region enrolling the subject, this treatment will be trientine hydrochloride, penicillamine, or Zn, or a combination of both chelation and Zn therapy, administered according to standard regimens.

Experimental: 15-60 mg WTX101 to subjects treated ≤28 days with SOC
Subjects who are treatment naïve or have been previously treated with chelation or Zn therapy or a combination of both chelation and Zn therapy for ≤28 days will be treated with 15 mg QOD to 60 mg QD of WTX101 by oral administration.
Drug: WTX101
WTX101 administered orally in 15 mg tablets

Active Comparator: SOC for subjects treated with SOC ≤28 days prior
Subjects who are treatment naïve or have been previously treated with chelation or Zn therapy or a combination of both chelation and Zn therapy for ≤28 days will initiate or continue SOC therapy.
Drug: SOC Therapy
Subjects randomized to receive SOC treatment will continue their current therapy or initiate therapy with chelation, Zn, or a combination of both chelation and Zn therapy. Depending on the site/region enrolling the subject, this treatment will be trientine hydrochloride, penicillamine, or Zn, or a combination of both chelation and Zn therapy, administered according to standard regimens.




Primary Outcome Measures :
  1. Evaluate the efficacy of WTX101 using standard of care as comparator and copper as the control assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non-ceruloplasmin-bound copper levels [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the efficacy of WTX101 administered for 48 weeks, compared to standard of care, on copper control in Wilson Disease subjects aged 18 and older. Copper control will be assessed in terms of the percentage change from baseline (Day 1) to 48 weeks in non-ceruloplasmin-bound copper levels. For WTX101-treated subjects, the non-ceruloplasmin-bound copper level will be corrected for the amount of copper bound to the WTX101 tripartite complex.


Secondary Outcome Measures :
  1. Safety and tolerability of individualized dosing of WTX101 by descriptive statistics via the Safety Analysis Set dataset [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Safety and tolerability will be determined over the course of the study period by descriptive statistics via the Safety Analysis Set dataset. This dataset includes all subjects who received at least 1 dose of randomized treatment. Subjects will be summarized according to the treatment actually received.

  2. Effects of WTX101 on hepatic status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]

    Evaluate the effects of WTX101 on hepatic status assessed by the Model for End-Stage Liver Disease (MELD) score. The MELD uses the subject's values for serum bilirubin, serum creatinine, and the international normalized ratio for prothrombin time (INR) to predict survival. It is calculated according to the following formula:

    MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43.


  3. Effects of WTX101 on disability status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on disability status assessed by the Unified WD Rating Scale (UWDRS) Part II which consists of a historical review of daily activity items and is reported by the subject or family.

  4. Effects of WTX101 on neurological status [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on neurological status assessed by the Unified WD Rating Scale (UWDRS) Part III which consists of a neurological examination performed by a blinded neurologist.

  5. Global effects of WTX101 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) [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the global effects of WTX101 on clinical symptoms performed by the Investigator using a composite assessment which include the Clinical Global Impression-Improvement Scale (a 7-point scale that assess how much the subject's illness has improved or worsened relative to a baseline and rated from 1 to 7) and the Clinical Global Impression-Severity Scale (a 7-point scale that assess severity of a subject's illness relative to a baseline and rated from 1 to 7).

  6. Effects of WTX101 on NCC responder rate [ Time Frame: Change from baseline (Day 1) to 48 weeks ]
    Evaluate the effects of WTX101 on the NCC responder rate



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects who meet all of the following criteria will be eligible to participate in the study:

  • Established diagnosis of WD by Leipzig-Score ≥4 documented by testing as outlined in the 2012 European Association for the Study of Liver WD Clinical Practice Guidelines;
  • Treatment for >28 days for WD with chelation therapy (ie, penicillamine, trientine hydrochloride), Zn therapy, or a combination of a chelator and Zn; OR Treatment naïve or treatment for ≤28 days for WD with chelation therapy (ie, penicillamine, trientine hydrochloride), Zn therapy, or a combination of a chelator and Zn;
  • Willing and able to give informed consent for participation in the study;
  • Male or female subjects, aged 18 years or older as of signing the informed consent form (ICF);
  • Able to understand and willing to comply with study procedures, restrictions, and requirements, as judged by the Investigator;
  • Willing to undergo ≥48-hour washout from current WD treatment;
  • Adequate venous access to allow collection of required blood samples;
  • Willing to avoid use of vitamins and/or minerals containing Cu, Zn, or Mo throughout the study duration;
  • Willing to avoid intake of foods and drinks with high contents of Cu throughout the study duration;
  • Females of childbearing potential will be included if they are either sexually inactive (abstinent) for 14 days prior to the first WTX101 dose and continuing through 28 days after the last WTX101 dose, or using 1 of the following highly effective birth control methods (ie, results in <1% failure rate when used consistently and correctly):

    1. Intrauterine device (without Cu) in place for at least 3 months prior to the first WTX101 dose and throughout the study;
    2. Surgical sterilization of the partner (vasectomy for 6 months minimum);
    3. Combined (estrogen or progestogen containing) hormonal contraception associated with the inhibition of ovulation (either oral, intravaginal, or transdermal) for at least 3 months prior to the first WTX101 dose and throughout the study;
    4. Progestogen only hormonal contraception associated with the inhibition of ovulation (either oral, injectable, or implantable) for at least 3 months prior to the first WTX101 dose and throughout the study;
    5. Intrauterine hormone releasing system for at least 3 months prior to the first WTX101 dose and throughout the study; or
    6. Bilateral tubal occlusion for at least 6 months prior to the first WTX101 dose;

      • Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. In this trial, abstinence is only acceptable if in line with the subject's preferred and usual lifestyle; and
      • Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. As well, female condom and male condom should not be used together;
  • Females of childbearing potential agree to remain sexually inactive or to keep the same birth control method for at least 28 days following the last dose;
  • A female of non-childbearing potential must have undergone 1 of the following sterilization procedures at least 6 months prior to the first WTX101 dose:

    1. Hysteroscopic sterilization;
    2. Bilateral tubal ligation or bilateral salpingectomy;
    3. Hysterectomy; or
    4. Bilateral oophorectomy; OR be postmenopausal with amenorrhoea for at least 1 year prior to the first WTX101 dose and follicle stimulating hormone serum levels consistent with postmenopausal status;
  • A non-vasectomized male subject agrees to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days beyond the last dose of study drug. For a vasectomized male who has had his vasectomy 6 months or more prior to study start, it is required that they use a condom during sexual intercourse. A male who has been vasectomized less than 6 months prior to study start must follow the same restrictions as a non-vasectomized male;

    • Note: Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. In this trial, abstinence is only acceptable if in line with the subject's preferred and usual lifestyle; and
    • Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea method are not acceptable methods of contraception. As well, female condom and male condom should not be used together; and
  • If male, agrees not to donate sperm from the first WTX101 dose until 90 days after dosing.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participation in the study:

  • Decompensated hepatic cirrhosis;
  • MELD score >13;
  • Modified Nazer score >7;
  • Clinically significant gastrointestinal bleed within past 3 months;
  • Alanine aminotransferase >2 × upper limit of normal (ULN) for subjects treated for >28 days with WD therapy (Cohort 1);
  • Alanine aminotransferase >5 × ULN for treatment naïve subjects or subjects who have been treated for ≤28 days (Cohort 2);
  • Marked neurological disease requiring either nasogastric feeding or intensive inpatient medical care;
  • Severe anaemia with a hemoglobin <9 g/dL;
  • Participation in a clinical study of an experimental or unapproved/unlicensed therapy at the same time or within the 4 weeks prior to this Screening Visit;
  • History of seizure activity within 6 months of study start;
  • Pregnant (or women who are planning to become pregnant) or lactating women;
  • Known sensitivity to WTX101, WTX101 excipients (anhydrous di-calcium phosphate, anhydrous sodium carbonate), or any of the ingredients contained in WTX101 or related compounds;
  • Active infection with hepatitis B virus (positive hepatitis B surface antigen) or C virus (subjects with positive hepatitis C antibody result would require confirmation of active disease with a positive hepatitis C polymerase chain reaction test), or seropositivity for human immunodeficiency virus;
  • Any disability acquired from trauma or another illness that, in the opinion of the Investigator, could interfere with evaluation of disability due to WD;
  • Previous treatment with tetrathiomolybdate;
  • Major systemic disease or other illness that would, in the opinion of the Investigator, compromise subject safety or interfere with the collection or interpretation of study results;
  • In the opinion of the Investigator, the subject is likely to be non-compliant or uncooperative during the study; or
  • Any deviation in laboratory values that are confirmed on re-examination to be clinically significant by the Investigator that would jeopardize the safety of the subject or impact the validity of the study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03403205


  Hide Study Locations
Locations
United States, California
University of California, Los Angeles (UCLA) - David Geffen School of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Diane Yang    310-206-3356    ddyang@mednet.ucla.edu   
Principal Investigator: Jeff Bronstein         
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
Contact: Sarah Swift    203-737-7683    sarah.swift@yale.edu   
Principal Investigator: Michael Schilsky         
United States, Illinois
Northwestern University The Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Contact: ZsaZsa Brown    312-503-4121    zsazsa.brown@northwestern.edu   
Principal Investigator: Danny Bega         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Elizabeth Wu    734-764-4048    elizwu@med.umich.edu   
Principal Investigator: Fred Askari         
United States, Tennessee
Vanderbilt University Medical Center Recruiting
Nashville, Tennessee, United States, 37240-7915
Contact: Tricia McKinney    615-875-7394    tricia.r.mckinney@vumc.org   
Principal Investigator: Peter Hedera         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Tiffany Hunsucker    832-355-1450    tzgabay@bcm.edu   
Principal Investigator: Norman Sussman         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: James DeLappe    206-987-5634    james.DeLappe@seattlechildrens.org   
Principal Investigator: Sihoun Hahn         
Austria
Medical University Graz Recruiting
Graz, Austria, 8036
Contact: Andreas Posch    +43 316 385 81156    andreas.posch@medunigraz.at   
Principal Investigator: Rudolph Stauber         
Medical University Innsbruck Recruiting
Innsbruck, Austria, 6020
Contact: Klemens Zotter    +43 512 504 82830    klemens.zotter@tirol-kliniken.at   
Principal Investigator: Heinz Zoller         
Medizinische Universitat Wien, Innere Medizin III Recruiting
Wien, Austria, 1090
Contact: Anna Swoboda    +43 (0)1 40400-47440    Anna.swoboda@meduniwien.ac.at   
Principal Investigator: Peter Ferenci         
Czechia
Vseobecna fakultni nemocnice v Praze Not yet recruiting
Praha 2, Czechia, 128 08
Contact: Radan Bruha    (00 420) 224 962 506    bruha@cesnet.cz   
Principal Investigator: Radan Bruha         
France
CHU Lyon- Hopital Femme- Mere-Enfant Not yet recruiting
Bron, France, 69677
Contact: Abdelouahed BelMalih       Abdelouahed.belmalih@chu-lyon.fr   
Principal Investigator: Anne-Sophie Brunet         
Hopital Lariboisiere Not yet recruiting
Paris, France, 75010
Contact: Nadege Tinant       nadege.tinant@aphp.fr   
Principal Investigator: Aurelia Poujois         
Germany
Universitaetsklinikum Carl Gustav Carus Dresden an der Technischen Universität Dresden Recruiting
Dresden, Germany, 01307
Contact: Jochen Schaefer    +493514584648    Jochen.Schaefer@uniklinikum-dresden.de   
Principal Investigator: Ulrike Reuner         
Ifi - Studien und Projekte GmbH Recruiting
Hamburg, Germany, 20099
Contact: Petra Lange    +49402840760201    lange@ifi-medizin.de   
Principal Investigator: Peter Buggisch         
University Hospital Heidelberg Recruiting
Heidelberg, Germany, 69120
Contact: Andrea Langel    +49 6221 56 8388    Andrea.Langel@med.uni-heidelberg.de   
Principal Investigator: Karl-Heinz Weiss         
Universitatsklinikum der Universitaet Leipzig Recruiting
Leipzig, Germany, 04103
Contact: Carolin Straube    +493419712328    carolin.straube@medizin.uni-leipzig.de   
Principal Investigator: Johannes Wiegand         
Hungary
Semmelweis Egyetem Not yet recruiting
Budapest, Hungary, 1083
Contact: Daniel Nemeth    36205477786    neemethd@gmail.com   
Principal Investigator: Ferenc Szalay         
Israel
Carmel Medical Center Not yet recruiting
Haifa, Israel, 34362
Contact: Orly Azulay    972522976633    orlyaz@clalit.org.il   
Principal Investigator: Eli Zuckerman         
Hadassah University Hospital Not yet recruiting
Jerusalem, Israel, 91120
Contact: Rami Ghantous    97226777451    ghantous@hadassah.org.il   
Principal Investigator: Rifaat Safadi         
Holy Family Hospital Not yet recruiting
Nazareth, Israel, 91120
Contact: Rifaat Safadi    +972 50 8573574    Safadi@hadassah.org.il   
Principal Investigator: Rifaat Safadi         
Sheba Medical Center Not yet recruiting
Tel Hashomer, Israel, 5265601
Contact: Avishag Hassid    972-35307176    avishag.hassid@sheba.health.gov.il   
Principal Investigator: Ziv Ben Ari         
Italy
Ospedale San Paolo - Milano Not yet recruiting
Milano, Italy, 20142
Contact: Daniel Orellana    +39 02 503 23093    daniel.orellana.r@gmail.com   
Principal Investigator: Massimo Zuin         
Azienda Ospedaliera Universitaria Federico II Not yet recruiting
Napoli, Italy, 80131
Contact: Giusy Ranucci       giusyranucci@hotmail.it   
Principal Investigator: Raffaele Iorio         
Azienda Ospedaliera di Padova Not yet recruiting
Padova, Italy, 35121
Contact: Alessandra Rigo    0498212893    alessandra.rigo@hotmail.it   
Principal Investigator: Renata D'Incà         
Azienda Ospedaliera Universitaria OO.RR. San Giovanni di Dio - Ruggi d'Aragona Not yet recruiting
Salerno, Italy, 84131
Contact: Susan Ainscough    +39 089673703    ricercaparkinson@gmail.com   
Principal Investigator: Maria Pellecchia         
Poland
Instytut Psychiatrii i Neurologii Recruiting
Warszawa, Poland, 02-957
Contact: Tomasz Litwin    0048228427683    tomlit@medprakt.pl   
Principal Investigator: Anna Czlonkowska         
Spain
Hospital Universitario Puerta de Hierro Majadahonda Recruiting
Majadahonda, Spain, 28222
Contact: Maria Gomez    607945067    mgadelhuph@gmail.com   
Principal Investigator: Jose Luis Calleja Panero         
Corporacio Sanitaria Parc Tauli - Hospital de Sabadell Not yet recruiting
Sabadell, Spain, E-08208
Contact: Ariadna Figuerola    0034937231010 ext 22070    AFiguerola@tauli.cat   
Principal Investigator: Mercedes Vergara Gomez         
United Kingdom
Queen Elizabeth Hospital Birmingham Not yet recruiting
Birmingham, United Kingdom, B15 2PR
Contact: Claire Arthur    +44 121 507 4588    claire.arthur@uhb.nhs.uk   
Principal Investigator: David Nicholl         
Addenbrooke's Hospital Not yet recruiting
Cambridge, United Kingdom, CB2 0OQ
Contact: Janeane Hails    01223 216109    janeane.hails@addenbrookes.nhs.uk   
Principal Investigator: William Griffiths         
Royal Surrey County Hospital Not yet recruiting
Guildford, United Kingdom, GU2 7XX
Contact: Louise Gallagher    +44 1483571122    louise.gallagher1@nhs.net   
Principal Investigator: Aftab Ala         
Sponsors and Collaborators
Wilson Therapeutics AB
Investigators
Study Director: Carl Bjartmar, MD, PhD Wilson Therapeutics AB

Responsible Party: Wilson Therapeutics AB
ClinicalTrials.gov Identifier: NCT03403205     History of Changes
Other Study ID Numbers: WTX101-301
First Posted: January 18, 2018    Key Record Dates
Last Update Posted: July 2, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Hepatolenticular Degeneration
Liver Diseases
Digestive System Diseases
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Movement Disorders
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors