Clinical trial NCT04973137: A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients with AL Amyloidosis
Official title: A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled, Efficacy and Safety Study of Birtamimab Plus Standard of Care Vs. Placebo Plus Standard of Care in Mayo Stage IV Subjects with Light Chain (AL) Amyloidosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Light Chain (AL) Amyloidosis
Keywords: Light Chain (AL) Amyloidosis
Mayo Stage IV
birtamimab
Lead sponsor: Prothena Biosciences Ltd.
Sponsor class: INDUSTRY
First posted: 2021-07-22
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A Phase 3 study to evaluate the efficacy and safety of birtamimab plus standard of care compared to placebo plus standard of care in Mayo Stage IV patients with AL amyloidosis.

Detailed description: This is a Phase 3 multicenter, global, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of birtamimab in Mayo Stage IV patients with AL amyloidosis (i.e., Double-blind Phase), followed by a long-term, open-label extension (i.e., Open-label Extension \[OLE\] Phase). The primary objective of the Double-blind Phase is to evaluate the efficacy of birtamimab by assessing time to all-cause mortality. All patients will receive bortezomib-containing chemotherapy regimen as standard of care.

For the Double-blind Phase of the study, approximately 220 newly diagnosed Mayo Stage IV patients with AL amyloidosis will be enrolled and randomized in a 2:1 ratio to birtamimab or placebo. Subjects will remain on study until study completion, when the pre-defined number of events (all-cause mortality) have been reached.

After completion of the Double-blind Phase, eligible subjects may enter the optional OLE Phase, in which all subjects will receive open-label birtamimab treatment, regardless of Double-blind Phase randomized treatment assignment. Treatment in the OLE Phase will continue for an additional 24 months or until birtamimab is commercially available in a subject's country of residence, whichever occurs first (in accordance with country-specific regulations). The primary objective of the OLE Phase is to evaluate the long-term safety of birtamimab plus standard of care in Mayo Stage IV subjects with AL amyloidosis.

Eligibility criteria: Key Inclusion Criteria for Double-blind Phase:

* Aged ≥18 years and legal age of consent according to local regulations
* Newly diagnosed and AL amyloidosis treatment-naïve with cardiac involvement
* Confirmed diagnosis of AL amyloidosis
* Confirmed Mayo Stage IV AL Amyloidosis as defined by NT-proBNP ≥1800 pg/mL and Troponin-T ≥0.025 ng/mL or high sensitivity cardiac troponin T≥40ng/L and dFLC ≥18 mg/dL
* Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly

Inclusion Criteria for Open-label (OLE) Phase:

* Must not have discontinued treatment in Double-blind Phase
* WOCBP must have a negative pregnancy test and must agree to use highly effective contraception through 90 days following last study drug administration
* Male subjects must be surgically sterile or agree to use highly effective contraception through 90 days following last study drug administration
* Ability to understand and willingness to sign an ICF prior to initiating the OLE Phase

Key Exclusion Criteria for Double-blind Phase:

* Non-AL amyloidosis
* NT-proBNP \>8500 pg/mL
* Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma except for malignancy biomarker of involved/uninvolved serum free light chain ratio ≥100
* Subject is eligible for and plans to undergo ASCT or organ transplant during the study
* Myocardial infarction, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
* Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area \<1.0 cm2) or severe congenital heart disease
* ECG evidence of acute ischemia or active conduction system abnormalities
* Prior treatment with hematopoietic growth factors, transfusions of blood or blood products within 1 week of Month 1-Day 1
* Prior radiotherapy within 4 weeks of Month 1-Day 1
* Prior treatment with plasma cell-directed chemotherapy, birtamimab, daratumumab, 11- 1F4, anti-serum amyloid P antibody, doxycycline for amyloid, or other investigational treatment directed at amyloid
* Waldenström's macroglobulinemia and/or immunoglobulin M monoclonal gammopathy

Exclusion Criteria for OLE Phase:

* Any medical condition or clinically significant abnormality on physical, neurological, laboratory, vital signs, or ECG examination that precludes treatment with birtamimab or participation in the study, in the medical judgment of the Investigator
* Symptomatic orthostatic hypotension that in the medical judgment of the Investigator would interfere with subject's ability to safely receive treatment or complete study assessments
* History of Grade ≥3 infusion-related AEs during the Double-blind Phase or hypersensitivity to birtamimab
* Unable or unwilling to adhere to the study-specified procedures and restrictions
* Planning to use any other investigational treatment during the study

Primary outcomes:
measure: Time to all-cause mortality for the Double Blind Phase
timeFrame: Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached.
Secondary outcomes:
measure: 6MWT distance for the Double Blind Phase
timeFrame: Month 9
measure: Physical Component Summary score of the Short Form-36, version 2 for the Double Blind Phase
timeFrame: Month 9
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Hartford
country: United States
facility: St. Francis Hospital
state: Connecticut
city: North Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Trumbull
country: United States
facility: Smilow Cancer Hospital Care Center at Trumbull
state: Connecticut
city: Washington
country: United States
facility: MedStar Georgetown University Hospital
state: District of Columbia
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Bethesda
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Boston University School of Med.
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Rogel Cancer Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center - 38th Street
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: New York
country: United States
facility: New York University Langone Hospital - Long Island
state: New York
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health - Comprehensive Cancer Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Main Campus
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University College of Medicine
state: Ohio
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt - Ingram Cancer Center - Henry-Joyce Cancer Clinic
state: Tennessee
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Froedtert and Medical College of Wisconsin
state: Wisconsin
city: Kogarah
country: Australia
facility: SESLHD: St George Hospital
state: New South Wales
city: Auchenflower
country: Australia
facility: Icon Cancer Centre - Wesley
state: Queensland
city: South Brisbane
country: Australia
facility: Icon Cancer Center
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Salzburg
country: Austria
facility: Paracelsus Medical University
city: Salzburg
country: Austria
facility: Paracelsus Medical University
city: Vienna
country: Austria
facility: Medizinische Universität
city: Wien
country: Austria
facility: Medizinische Universität Wien
city: Oostende
country: Belgium
facility: Algemeen Ziekenhuis Sint-Jan Brugge-Oostende - Campus Sint-Jan
city: Oostende
country: Belgium
facility: AZ Sint-Jan Brugge-Oostende AV
city: Yvoir
country: Belgium
facility: Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
city: Yvoir
country: Belgium
facility: CHU UCL Namur (Site Godinne)
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Montréal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Brno
country: Czechia
facility: Fakultní Nemocnice Brno
state: Jihormoravsky Kraj
city: Ostrava-Poruba
country: Czechia
facility: Fakultni nemocnice ostrava
state: Moravian-Silesian
city: Praha
country: Czechia
facility: Všeobecná fakultní nemocnice v Praze
state: Prague
city: Odense
country: Denmark
facility: Odense Universitetshospital
state: Syddanmark
city: Tours Cedex 9
country: France
facility: Hôpital Bretonneau
state: Centre
city: Pessac
country: France
facility: Hôpital Haut-Lévêque
state: Gironde
city: Paris Cedex 15
country: France
facility: Hopital Necker
state: Ill-de-France
city: Paris
country: France
facility: Pitie-Salpêtrière Hospital
state: Ill-de-France
city: Vandœuvre-lès-Nancy
country: France
facility: Hôpitaux de Brabois
state: Lorraine
city: Toulouse Cedex 9
country: France
facility: Hopital Rangueil
state: Midi-Pyrenees
city: Lille
country: France
facility: Hôpital Claude Huriez
state: Nord
city: Nantes
country: France
facility: CHU Nantes
state: Pays de la Loire
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire Poitiers
state: Vienne
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Créteil
country: France
facility: Hôpitaux Universitaires Henri Mondor
city: Créteil
country: France
facility: Hopital Henri Mondor, Creteil
city: Limoges
country: France
facility: Centre Hospitalier Universitaire Limoges
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Wuerttemberg
city: Köln
country: Germany
facility: Uniklinik Köln
state: Baden-Württemberg
city: Mainz
country: Germany
facility: University Medicine Mainz
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Charité Campus Mitte
city: Athens
country: Greece
facility: Alexandra General Hospital
state: Attica
city: Thessaloníki
country: Greece
facility: Theagenio Anti-Cancer Hospital of Thessaloniki
state: Central Macedonia
city: Patra
country: Greece
facility: University Hospital of Patras
state: Peloponnese
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Klinikai Központ
state: Baranya
city: Szeged
country: Hungary
facility: Szent-Györgyi Albert Klinikai Központ
state: Csongrad
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Központ
state: Hajdu-Bihar County
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - I. sz. Belgyógyászati Klinika
city: Budapest
country: Hungary
facility: Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet
city: Cork
country: Ireland
facility: Cork University Hospital
state: Munster
city: Dublin
country: Ireland
facility: Cancer Clinical Trials and Research Unit, Beaumont Hospital
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
state: Haifa District
city: Haifa
country: Israel
facility: Rambam Medical Center
state: Haifa District
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
state: Jerusalem District
city: Ashkelon
country: Israel
facility: Rabin Medical Center - Beilinson Hospital
state: Southern District
city: Ashdod
country: Israel
facility: Samson Assuta Ashdod Hospital
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti Di Ancona
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
city: Brescia
country: Italy
facility: ASST Spedali Civili
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico Gaspare Rodolico - San Marco
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Pisa
country: Italy
facility: Azienda Ospedaliero-Universitaria Pisana
city: Roma
country: Italy
facility: Umberto I - Policlinico di Roma
city: Kita
country: Japan
facility: Kyoto Kuramaguchi Medical Center
state: Kyoto
city: Matsumoto
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Shimotsuke
country: Japan
facility: Jichi medical university hospital
state: Tochigi
city: Kuramoto
country: Japan
facility: Tokushima University Hospital
state: Tokushima
city: Shibuya-ku
country: Japan
facility: Red Cross Medical Center
state: Tokyo
city: Aichi
country: Japan
facility: Nagoya City University Hospital
city: Fukushima
country: Japan
facility: Fukushima Medical University Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
state: Gyeongsangbugdo
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
state: Jeollanam-do
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
state: Seoul Teugbyeols
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea - Seoul St. Mary's Hospital
city: Maastricht
country: Netherlands
facility: Maastricht Universitair Medisch Centrum
state: Limburg
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Gdańsk
country: Poland
facility: Klinika Hematologii i Transplantologii
state: Pomorskie
city: Szczecin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr 1
city: Braga
country: Portugal
facility: Hospital de Braga
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitário de Coimbra
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Balearic Islands
city: Palma De Mallorca
country: Spain
facility: Hospital Son Llatzer
state: Balearic Islands
city: Badalona
country: Spain
facility: Institut Català d'Oncologia - Hospital Germans Trias i Pujol
state: Barcelona
city: Santander
country: Spain
facility: University Hospital Marqués de Valdecilla
state: Cantabria
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra -Madrid
state: Navarra
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
state: Navarre
city: Tenerife
country: Spain
facility: Hospital Universitario de Canarias
state: Santa Cruz de Tenerife
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'hebron
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals
city: Girona
country: Spain
facility: Hospital Josep Trueta ICO Girona
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clínico
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic la Fe
city: Vila-real
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
state: Taipei
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Ankara
country: Turkey
facility: Ankara UMF
city: Ankara
country: Turkey
facility: Gazi University
city: Istanbul
country: Turkey
facility: Istanbul University Cerrahpasa Medical Faculty
city: İzmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital
state: England
city: High Heaton
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals
state: England
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
state: England
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
Study officials:
References: