AFFIRM-AL: A Study to Evaluate the Efficacy and Safety of Birtamimab in Mayo Stage IV Patients With AL Amyloidosis

Sponsor

Prothena Biosciences Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04973137

Collaborator

(none)

150

Enrollment

121

Locations

Arms

33.1

Anticipated Duration (Months)

1.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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 patients with AL amyloidosis in Mayo Stage IV.

Condition or Disease	Intervention/Treatment	Phase
Light Chain (AL) Amyloidosis	Drug: Birtamimab Other: Placebo Drug: Standard of Care Chemotherapy	Phase 3

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. The primary objective 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.

Approximately 150 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 30, 2021

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Birtamimab plus Standard of Care Chemotherapy Intravenous administration of 24 mg/kg birtamimab every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator	Drug: Birtamimab Intravenous administration of 24 mg/kg birtamimab every 28 days Drug: Standard of Care Chemotherapy Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care
Placebo Comparator: Placebo plus Standard of Care Chemotherapy Intravenous 0.9% Saline administration as a placebo every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator	Other: Placebo Intravenous 0.9% Saline administration as a placebo every 28 days Drug: Standard of Care Chemotherapy Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care

Arm

Intervention/Treatment

Experimental: Birtamimab plus Standard of Care Chemotherapy

Intravenous administration of 24 mg/kg birtamimab every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator

Drug: Birtamimab

Intravenous administration of 24 mg/kg birtamimab every 28 days

Drug: Standard of Care Chemotherapy

Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care

Placebo Comparator: Placebo plus Standard of Care Chemotherapy

Intravenous 0.9% Saline administration as a placebo every 28 days. Drug: Standard of Care Chemotherapy. Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD) according to the institutional standard of care. Initiation of daratumumab at randomization allowed at the discretion of the investigator

Other: Placebo

Intravenous 0.9% Saline administration as a placebo every 28 days

Drug: Standard of Care Chemotherapy

Bortezomib-containing chemotherapy regimen (e.g. cyclophosphamide, bortezomib, and dexamethasone (CyBorD)) according to the institutional standard of care

Outcome Measures

Primary Outcome Measures

Time to all-cause mortality [Time from the first dose of study drug until the pre-defined number of events (all-cause mortality) have been reached.]
Comparison of time to all-cause mortality for birtamimab and placebo control.

Secondary Outcome Measures

Physical Component Summary (PCS) score of the Short Form-36, version 2 (SF-36v2) [Month 9]
The Short Form-36, version 2 (SF-36v2) is a 36-item self-administered quality-of-life (QoL) questionnaire that measures health on functional status, well-being, and overall evaluation of health. Higher SF-36 scores represent better health. The Physical Component Summary (PCS) is derived primarily from questions regarding physical functioning, physical problems, bodily pain, and general health questions
6MWT distance [Month 9]
Change from baseline to Month 9 in the 6-Minute Walk Test (6MWT) distance

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

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 >0.03 ng/mL and dFLC ≥18 mg/dL
Planned first-line chemotherapy contains bortezomib administered subcutaneously weekly.

Key Exclusion Criteria:

Non-AL amyloidosis.
NT-proBNP >8500 pg/mL.
Meets the International Myeloma Working Group (IMWG) definition of multiple myeloma
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Francis Hospital	Hartford	Connecticut	United States	06105
2	Yale Cancer Center	North Haven	Connecticut	United States	06473
3	Smilow Cancer Hospital Care Center at Trumbull	Trumbull	Connecticut	United States	06611
4	Johns Hopkins University	Bethesda	Maryland	United States	20814-1422
5	Boston University School of Med.	Boston	Massachusetts	United States	02118
6	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
7	University of Michigan Rogel Cancer Center	Ann Arbor	Michigan	United States	48109
8	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
9	Mayo Clinic - Rochester	Rochester	Minnesota	United States	55905
10	Saint Lukes Hospital of Kansas City	Kansas City	Missouri	United States	64111
11	Roswell Park Comprehensive Cancer Center	Buffalo	New York	United States	14263
12	Perlmutter Cancer Center - 38th Street	New York	New York	United States	10016
13	Duke Clinical Research Institute	Durham	North Carolina	United States	27705
14	Wake Forest Baptist Health - Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157
15	Cleveland Clinic Main Campus	Cleveland	Ohio	United States	44195
16	The Ohio State University College of Medicine	Columbus	Ohio	United States	43210
17	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
18	Baylor University Medical Center	Dallas	Texas	United States	75246
19	Froedtert and Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
20	SESLHD: St George Hospital	Kogarah	New South Wales	Australia	2217
21	Icon Cancer Centre - Wesley	Auchenflower	Queensland	Australia	4066
22	Icon Cancer Center	South Brisbane	Queensland	Australia	4101
23	Royal Adelaide Hospital	Adelaide	South Australia	Australia	5000
24	Eastern Health	Box Hill	Victoria	Australia	3128
25	Monash Medical Centre	Clayton	Victoria	Australia	3168
26	Barwon Health	Geelong	Victoria	Australia	3220
27	Royal Perth Hospital	Perth	Western Australia	Australia	6000
28	Tom Baker Cancer Centre	Calgary	Alberta	Canada	T2N4N2
29	Royal Victoria Hospital	Montréal	Quebec	Canada	H3A1A1
30	Fakultní Nemocnice Brno	Brno	Jihormoravsky Kraj	Czechia	62500
31	Fakultni nemocnice ostrava	Ostrava-Poruba	Moravian-Silesian	Czechia	70852
32	Všeobecná fakultní nemocnice v Praze	Praha	Prague	Czechia	12808
33	Odense Universitetshospital	Odense	Syddanmark	Denmark	5000
34	Hôpital Bretonneau	Tours Cedex 9	Centre	France	37044
35	Hopital Necker	Paris Cedex 15	Ill-de-France	France	75743
36	Pitie-Salpêtrière Hospital	Paris	Ill-de-France	France	75013
37	Hôpitaux de Brabois	Vandœuvre-lès-Nancy	Lorraine	France	54511
38	Hopital Rangueil	Toulouse Cedex 9	Midi-Pyrenees	France	31059
39	Hôpital Claude Huriez	Lille	Nord	France	59037
40	CHU Nantes	Nantes	Pays De La Loire	France	44093
41	Centre Hospitalier Universitaire Poitiers	Poitiers	Vienne	France	86021
42	Centre Hospitalier Universitaire Limoges	Limoges		France	87000
43	Universitätsklinikum Heidelberg	Heidelberg	Baden-Wuerttemberg	Germany	69120
44	Uniklinik Köln	Köln	Baden-Württemberg	Germany	50937
45	University Medicine Mainz	Mainz	Rheinland-Pfalz	Germany	55131
46	Charité Campus Mitte	Berlin		Germany	10117
47	Alexandra General Hospital	Athens	Attica	Greece	11528
48	Theagenio Anti-Cancer Hospital of Thessaloniki	Thessaloníki	Central Macedonia	Greece	54007
49	University Hospital of Patras	Patra	Peloponnese	Greece	26504
50	Pécsi Tudományegyetem Klinikai Központ	Pécs	Baranya	Hungary	7622
51	Szent-Györgyi Albert Klinikai Központ	Szeged	Csongrad	Hungary	6725
52	Debreceni Egyetem Klinikai Központ	Debrecen	Hajdu-Bihar County	Hungary	4032
53	Semmelweis Egyetem - I. sz. Belgyógyászati Klinika	Budapest		Hungary	1087
54	Dél-pesti Centrumkórház - Országos Hematológiai és Infektológiai Intézet	Budapest		Hungary	1097
55	Cork University Hospital	Cork	Munster	Ireland	T12 DFK4
56	Bnai Zion Medical Center	Haifa	Haifa District	Israel	31048
57	Rambam Medical Center	Haifa	Haifa District	Israel	3109601
58	Hadassah Medical Center	Jerusalem	Jerusalem District	Israel	9112001
59	Rabin Medical Center - Beilinson Hospital	Ashkelon	Southern District	Israel	7830604
60	Samson Assuta Ashdod Hospital	Ashdod		Israel	7747629
61	Barzilai Medical Center	Ashkelon		Israel	7830604
62	Carmel Medical Center	Haifa		Israel	3436212
63	Azienda Ospedaliero Universitaria Ospedali Riuniti Di Ancona	Ancona		Italy	60020
64	Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi	Bologna		Italy	40138
65	ASST Spedali Civili	Brescia		Italy	25123
66	Azienda Ospedaliero - Universitaria - Policlinico - Vittorio Emanuele	Catania		Italy	95100
67	Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
68	Azienda Ospedaliero-Universitaria Pisana	Pisa		Italy	56124
69	Umberto I - Policlinico di Roma	Roma		Italy	00161
70	The Jieki University Kashiwa Hospital	Kashiwa	Chiba	Japan
71	Kyoto Kuramaguchi Medical Center	Kita	Kyoto	Japan
72	Shinshu University Hospital	Matsumoto	Nagano	Japan	390-0802
73	Jichi medical university hospital	Shimotsuke	Tochigi	Japan
74	Tokushima University Hospital	Kuramoto	Tokushima	Japan
75	Red Cross Medical Center	Shibuya-ku	Tokyo	Japan	150-8935
76	Nagoya City University Hospital	Aichi		Japan
77	Fukushima Medical University Hospital	Fukushima		Japan	960-1247
78	Keimyung University Dongsan Hospital	Daegu	Gyeongsangbugdo	Korea, Republic of	42601
79	Chonnam National University Hwasun Hospital	Hwasun-gun	Jeollanam-do	Korea, Republic of	58128
80	Severance Hospital	Seoul	Seoul Teugbyeols	Korea, Republic of	120-752
81	Pusan National University Hospital	Busan		Korea, Republic of	49241
82	Kosin University Gospel Hospital	Busan		Korea, Republic of	602702
83	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
84	Seoul National University Hospital	Seoul		Korea, Republic of	03080
85	Samsung Medical Center	Seoul		Korea, Republic of	06351
86	The Catholic University of Korea - Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06351
87	Kangbuk Samsung Hospital	Seoul		Korea, Republic of	110-130
88	Maastricht Universitair Medisch Centrum	Maastricht	Limburg	Netherlands	6229HX
89	Universitair Medisch Centrum Groningen	Groningen		Netherlands	9713GZ
90	UMC Utrecht	Utrecht		Netherlands	3584CX
91	Uniwersyteckie Centrum Kliniczne w Gdańsku	Gdańsk	Pomorskie	Poland	80-214
92	Hospital de Braga	Braga		Portugal	4710-243
93	Centro Hospitalar e Universitário de Coimbra	Coimbra		Portugal	3000-075
94	Centro Hospitalar Universitário Lisboa Norte - Hospital De Santa Maria	Lisboa		Portugal	1649-028
95	Hospital Universitario Son Espases	Palma De Mallorca	Balearic Islands	Spain	07120
96	Hospital Son Llatzer	Palma De Mallorca	Balearic Islands	Spain	07198
97	Institut Català d'Oncologia - Hospital Germans Trias i Pujol	Badalona	Barcelona	Spain	08916
98	University Hospital Marqués de Valdecilla	Santander	Cantabria	Spain	39008
99	Clinica Universidad de Navarra -Madrid	Pamplona	Navarra	Spain
100	Clinica Universidad de Navarra - Pamplona	Pamplona	Navarre	Spain	31008
101	Hospital Universitario de Canarias	Tenerife	Santa Cruz De Tenerife	Spain	38320
102	Hospital Universitari Vall d'hebron	Barcelona		Spain	08035
103	Hospital Clinic of Barcelona	Barcelona		Spain	08036
104	Institut Català d'Oncologia - Hospital Duran i Reynals	Barcelona		Spain	08908
105	Hospital Josep Trueta ICO Girona	Girona		Spain	17007
106	Hospital Ramon y Cajal	Madrid		Spain	28034
107	Complejo Asistencial Universitario de Salamanca - Hospital Clínico	Salamanca		Spain	37007
108	Hospital Universitari i Politècnic la Fe	Valencia		Spain	46026
109	Hospital Universitario 12 de Octubre	Vila-real		Spain	1254
110	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan	833
111	Taipei Veterans General Hospital	Taipei		Taiwan	11217
112	Ankara UMF	Ankara		Turkey	06100
113	Gazi University	Ankara		Turkey	06500
114	Istanbul University Cerrahpasa Medical Faculty	Istanbul		Turkey	34320
115	Ege Universitesi Tip Fakultesi	İzmir		Turkey	35100
116	University Hospitals Birmingham NHS Foundation Trust - Queen Elizabeth Hospital	Birmingham	England	United Kingdom	B152SY
117	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	High Heaton	England	United Kingdom	NE77DN
118	Barts Health NHS Trust	London	England	United Kingdom	EC1A7BE
119	Univiersity College London Hospitals	London	England	United Kingdom	NW12PG
120	Manchester University NHS Foundation Trust	Manchester	England	United Kingdom	M139WL
121	Nottingham University Hospitals NHS Trust	Nottingham	England	United Kingdom	NG51PB

Sponsors and Collaborators

Prothena Biosciences Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Prothena Biosciences Ltd.

ClinicalTrials.gov Identifier:

NCT04973137

Other Study ID Numbers:

NEOD001-301

First Posted:

Jul 22, 2021

Last Update Posted:

Aug 9, 2022

Last Verified:

Aug 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

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

Yes

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

Keywords provided by Prothena Biosciences Ltd.

Light Chain (AL) Amyloidosis

Mayo Stage IV

birtamimab

Additional relevant MeSH terms:

Amyloidosis

Study Results

No Results Posted as of Aug 9, 2022