A study to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who completed Study NEOD001 201

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2016-004664-18-ES
• Date of registration: 29/05/2017
• Prospective Registration: Yes
• Primary sponsor: Prothena Therapeutics Limited
• Public title: A study to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who completed Study NEOD001 201
• Scientific 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)
• Date of first enrolment: 31/07/2017
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004664-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Austria, France, Germany, Greece, Israel, Italy, Spain, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Prothena Biosciences Inc

• Name: Clinical Trial Information Desk
• Affiliation: Prothena Biosciences Inc

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion Criteria (subjects must meet all of the following criteria):
1. Completed the EOS 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 (WOCBP) must have a negative pregnancy test during Screening and must agree to use highly effective physician-approved contraception (Appendix 2) 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 (Appendix 2) from Screening to 90 days following the last study drug administration
6. Ability to understand and willingness to sign an informed consent form (ICF) prior to initiation of any study procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Exclusion Criteria (subjects must not meet any of the following 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, vi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

The objective of this study is to evaluate the long-term safety and efficacy of NEOD001 in subjects with AL amyloidosis who completed Study NEOD001 201
MedDRA version: 20.0 Level: PT Classification code 10036673 Term: Primary amyloidosis System Organ Class: 10021428 - Immune system disorders

Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Intervention(s)

Product Name: NEOD001
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: NEOD001
Other descriptive name: Humanized IgG1, kappa anti-serum amyloid A and anti-AL amyloid antibody
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: Not applicable

Timepoint(s) of evaluation of this end point: Up to 38 months or until the study is terminated. Refer to Study Protocol, Table 1 Schedule of Assessments.

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

Primary end point(s): Safety Endpoints:
• Long-term safety and tolerability as assessed by vital signs, 12 lead ECGs, routine clinical laboratory assessments, and AEs
• Immunogenicity

Efficacy Endpoints:
• N-terminal pro-brain natriuretic peptide (NT-proBNP):
- Response (Appendix 3)
- Best response from baseline
- Change from baseline
• Change from baseline in troponin T
• Change from baseline in the Short Form-36 Health Survey version 2 (SF-36v2) Physical Component Score (PCS), Mental Component Score (MCS), and the 8 subscales
• Change from baseline in the 6-Minute Walk Test (6MWT) distance (meters)
• Progression-free survival
• For renal-evaluable subjects:
- Renal response (Appendix 3)
- Renal best response from baseline
- Change from baseline in creatinine, proteinuria, and eGFR
- Time to eGFR:
- =15 mL/min/1.73 m2 (Chronic Kidney Disease [CKD] Stage 5)
- <30 mL/min/1.73 m2 (CKD Stage 4)
- <60 mL/min/1.73 m2 (CKD Stage 3)
- Time to any worsening in CKD Stage
- Time to 40% reduction in eGFR
- Time to doubling of creatinine
• For peripheral neuropathy-evaluable subjects:
- Change from baseline in Neuropathy Impairment Score–Lower Limbs (NIS-LL) total score
- Peripheral neuropathy best response
- Peripheral neuropathy response (Appendix 3)
- For subjects with painful peripheral neuropathy in Study NEOD001-201 (i.e., baseline Visual Analog Scale – Pain Intensity [VASPI] score >0) change from baseline in the VASPI score
• For hepatic-evaluable subjects:
- Hepatic response (Appendix 3)
- Hepatic best response from baseline
• Time to all-cause mortality (overall survival)
• Frequency and duration of hospitalizations over the course of the study
• Change from baseline in the Kansas City Cardiomyopathy Questionnaire (KCCQ) subscores and overall summary score
• Time to progression for each organ (cardiac/NT-proBNP, renal, peripheral neuropathy, hepatic) separately and to any organ progression
• Eastern Cooperative Oncology Group (ECOG) Performance Status and New York Heart Association (NYHA) Class at each visit including any changes from baseline
• Change from baseline in serum free light chains (sFLCs), serum and 24-hour urine protein electrophoresis (PEP), and serum and urine immunofixation electrophoresis (IFE)
• Severity of disease-related symptoms including any changes from baseline
• Pharmacokinetics (PK)

Secondary Outcome(s)

Secondary end point(s): Not applicable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

2016-004664-18-DE

NEOD001-OLE251

Source(s) of Monetary Support

Prothena Therapeutics Limited