Study in Subjects With Light Chain (AL) Amyloidosis

AL Amyloidosis Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03154047
• Other study ID #: NEOD001-OLE251
• Status: Terminated
• Phase: Phase 2
• Start date: June 14, 2017
• Est. completion date: May 30, 2018

Study information

• Verified date: March 2019
• Source: Prothena Therapeutics Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 80
• Est. completion date: May 30, 2018
• Est. primary completion date: May 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• AL Amyloidosis
• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis

Intervention

Drug:
• NEOD001
humanized monoclonal antibody

Locations

Country	Name	City	State
Australia	Eastern Health (Box Hill Hospital)	Box Hill	Victoria
Australia	Westmead Hospital	Sydney	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Austria	Medizinische Universität Wien	Vienna
France	Hôpital Dupuytren - CHU Limoges	Limoges
France	Hôpital Pitié-Salpêtrière	Paris
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	University of Duisburg-Essen	Essen
Germany	Universitätsklinikum Hamburg-Eppendorf (UKE)	Hamburg
Germany	Universitätsklinikum Heidelberg	Heidelberg
Greece	Alexandra General Hospital of Athens	Athens
Greece	University Hospital of Patras	Patras
Israel	Hadassah Medical Center (HMC)	Jerusalem
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Spain	Hospital Clínic de Barcelona	Barcelona
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda
United Kingdom	Queen Elizabeth Hospital	Birmingham	England
United Kingdom	The Royal Free Hospital	London	England
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Chicago Medicine	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Mayo Clinic Hospital - Florida	Jacksonville	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic - Minnesota	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Prothena Therapeutics Ltd.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events	AEs are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome, or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.	Each subject's study participation may have been up to 36 months or until the study was terminated