Clinical trial NCT03154047: Study in Subjects With Light Chain (AL) Amyloidosis
Official title: A Phase 2b Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of NEOD001 in Subjects With Light Chain (AL) Amyloidosis Who Were Previously Enrolled in Study NEOD001-201 (PRONTO)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: AL Amyloidosis
Lead sponsor: Prothena Biosciences Ltd.
Sponsor class: INDUSTRY
First posted: 2017-05-15
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who have completed Study NEOD001-201.

Detailed description: Global, multicenter, Phase 2b, open-label extension study of subjects with AL amyloidosis who had a hematologic response to first-line treatment for their amyloidosis (e.g., chemotherapy, autologous stem cell transplant \[ASCT\]) and completed Study NEOD001-201. Subjects in this study may receive concomitant chemotherapy. Subject screening will occur during the 28 days prior to the first administration of study drug, which may overlap with the last visit in Study NEOD001-201. If all eligibility requirements are met, the subject will be enrolled and Screening assessments will be completed. Study visits will occur every 28 days based on scheduling from Month 1 Day 1. A ±5-day window is allowed for visits starting after Month 1. Subjects who discontinue study drug before the End of Study Visit (EOS) should have an Early Treatment Discontinuation Visit 30 (±5) days after their final administration of study drug. Each subject's study participation may be up to 38 months or until the study is terminated, whichever occurs first. The study consists of a Screening Phase (1 month), Treatment Phase (36 months), and EOS Visit (30 \[±5\] days after the last dose).

Eligibility criteria: Inclusion Criteria:

1. Completed the End of Study Visit in Study NEOD001-201
2. Adequate bone marrow reserve, hepatic and renal function, as demonstrated by:

   * Absolute neutrophil count (ANC) ≥1.0 × 109/L
   * Platelet count ≥75 × 109/L
   * Hemoglobin ≥9 g/dL
   * Total bilirubin ≤2 × upper limit of normal (ULN)
   * Aspartate aminotransferase (AST) ≤3 × ULN
   * Alanine aminotransferase (ALT) ≤3 × ULN
   * Alkaline phosphatase (ALP) ≤5 × ULN (except for subjects with hepatomegaly and isozymes specific to liver, rather than bone)
   * Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 as estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, or measured GFR ≥25 mL/min/1.73 m2
3. Systolic blood pressure 80-180 mmHg
4. Women of childbearing potential must have a negative pregnancy test during Screening and must agree to use highly effective physician-approved contraception from Screening to 90 days following the last study drug administration
5. Male subjects must be surgically sterile or must agree to use highly effective physician-approved contraception from Screening to 90 days following the last study drug administration
6. Ability to understand and willingness to sign an informed consent form prior to initiation of any study procedures

Exclusion Criteria:

1. Any new medical contraindication or clinically significant abnormality on physical, neurological, laboratory, vital signs, or electrocardiographic (ECG) examination (e.g., atrial fibrillation; with the exception of subjects for whom the ventricular rate is controlled) that precludes continuation or initiation of treatment with NEOD001 or participation in the study
2. 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
3. Myocardial infarction, uncontrolled angina, uncontrolled ventricular arrhythmias, or ECG evidence of acute ischemia, within 6 months prior to the Month 1-Day 1 Visit
4. Severe valvular stenosis (e.g., aortic or mitral stenosis with a valve area \<1.0 cm2) or severe congenital heart disease
5. ECG evidence of acute ischemia or active conduction system abnormalities with the exception of any of the following:

   * First degree atrioventricular (AV) block
   * Second degree AV block Type 1 (Mobitz Type 1/ Wenckebach type)
   * Right or left bundle branch block
   * Atrial fibrillation with a controlled ventricular rate (uncontrolled \[i.e., \>110 bpm\] ventricular rate is not allowed \[determined by an average of three beats in Lead II or 3 representative beats if Lead II is not representative of the overall ECG\])
6. Has not recovered (i.e., equivalent to a Common Terminology Criteria for Adverse Events \[CTCAE\] ≥Grade 2) from the clinically significant toxic effects of prior anticancer therapy. Exception: subjects who have received treatment with a proteasome inhibitor such as bortezomib may have CTCAE Grade 2 neuropathy.
7. Received any of the following within the specified time frame prior to the Month 1-Day 1 Visit:

   * Oral or IV antibiotics, antifungals, or antivirals within 1 week, with the exception of prophylactic oral agents. Note: In the event that a subject requires the chronic use of antivirals, Medical Monitor permission is required for entry into the study.
   * Hematopoietic growth factors, transfusions of blood or blood products within 1 week
   * Chemotherapy, radiotherapy, HDAC inhibitors, or other plasma cell directed therapy within 2 weeks
   * ASCT within 4 weeks (i.e., ASCT is allowed if it occurred before enrollment in Study NEOD001-201 or after completion of Study NEOD001-201 if it was at least 4 weeks before Month 1-Day 1 of this study)
   * Major surgery within 4 weeks (or within 2 weeks following consultation with and approval of Medical Monitor)
   * Planned organ transplant during the study
   * Any investigational agent, other than NEOD001, within 4 weeks
   * Any experimental imaging agent directed at amyloid within 2 weeks
8. Active malignancy with the exception of any of the following:

   * Adequately treated basal cell carcinoma, squamous cell carcinoma, or in situ cervical cancer
   * Adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years
   * Low-risk prostate cancer with Gleason score \<7 and prostate-specific antigen \<10 mg/mL
   * Any other cancer from which the subject has been disease-free for ≥2 years
9. History of Grade ≥3 infusion-related adverse events (AEs) or hypersensitivity to NEOD001
10. History of severe allergy to any of the components of NEOD001 such as histidine/L-Histidine, Trehalose, or Polysorbate 20
11. Currently known uncontrolled bacterial, viral, fungal, HIV, hepatitis B, or hepatitis C infection
12. Women who are breastfeeding
13. Any condition which could interfere with, or the treatment for which might interfere with, the conduct of the study or which would, in the opinion of the Investigator, unacceptably increase the subject's risk by participating in the study
14. Unable or unwilling to adhere to the study-specified procedures and restrictions
15. Subject is under legal custodianship

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Each subject's study participation may have been up to 36 months or until the study was terminated
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Hospital - Florida
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic - Minnesota
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Sydney
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Box Hill
country: Australia
facility: Eastern Health (Box Hill Hospital)
state: Victoria
city: Vienna
country: Austria
facility: Medizinische Universität Wien
city: Limoges
country: France
facility: Hôpital Dupuytren - CHU Limoges
city: Paris
country: France
facility: Hôpital Pitié-Salpêtrière
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
city: Essen
country: Germany
facility: University of Duisburg-Essen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf (UKE)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
city: Athens
country: Greece
facility: Alexandra General Hospital of Athens
city: Patras
country: Greece
facility: University Hospital of Patras
city: Jerusalem
country: Israel
facility: Hadassah Medical Center (HMC)
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro - Majadahonda
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: London
country: United Kingdom
facility: The Royal Free Hospital
state: England
Study officials:
References: