Clinical Trial: Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase Ia/Ib Study of Chimeric Fibril-Reactive Monoclonal Antibody 11-1F4 in Patients With AL Amyloidosis

Brief Summary:

The purpose of this study is to examine the tolerance, safety, pharmokinetics, and possible clinical benefit of the good manufacturing practice (GMP)-grade amyloid fibril-reactive chimeric (Ch) IgG1 mAb 11-1F4 in patients with amyloid light-chain (AL) amyloidosis.

The phase 1a part will involve at least 3 patients and a maximum of 18 patients. The first patient will receive the starting dose of the antibody and, if tolerated, the following patients will each receive (if tolerated) progressively higher doses of the antibody. Patients in part 1a of the trial will receive only one infusion of the drug. Patients treated in the phase 1a part receive lower dosage which might not be effective.

Once the maximal tolerated dosage is established during the phase 1a part, the investigators will accrue patients to the phase 1b part of the trial. Patients will receive 4 infusions, once each week for 4 weeks. Patients who were treated in the part 1a of the trial and showed no toxicity can be also treated in the part 1b of the trial. The first patient will receive the starting dose of the antibody and, if tolerated, the following patients will each receive (if tolerated) progressively higher doses of the antibody. When the investigators reach the maximum tolerated dose without toxicity, the investigators e will enroll another 4 patients to receive the same dose. If there are no toxicities, another 4 patients will be treated at the next dose level, and so forth. Patients treated in Phase 1b may receive lower dosages which might not be effective. The goal of Phase 1b is to establish the tolerance and possible beneficial effects of 11-1F4. If successful, treatment with this antibody would represent a novel approach in the care of individuals with AL amyloidosis.

Funding Source - FDA OOPD

Detailed Summary: Presently, treatment of patients with amyloid light chain (AL) amyloidosis is limited to reducing production of the amyloid-forming light-chain protein by giving conventional or high-dose (with stem cell transplant) anti-plasma cell chemotherapy, as used for patients with multiple myeloma. Although this approach has extended survival, the prognosis remains poor due to the persistence or progression of the amyloid deposits in vital organs, such as the heart or kidney. A different treatment strategy would be to attempt to reduce and/or eliminate these deposits. This study evaluates this by administering an anti-amyloid monoclonal antibody, 11-1F4. This compound has been shown to reduce/destroy this material in an experimental animal model of amyloidosis.
Sponsor: Suzanne Lentzsch, MD

Current Primary Outcome: Maximum Tolerated Dose (MTD) of Ch mAb 11-1F4 [ Time Frame: 2 years approximately ]

Original Primary Outcome: To establish the maximum tolerated dose of Ch mAb 11-1F4 [ Time Frame: 2 years (approximately) ]

Current Secondary Outcome:

• Number of subjects with positive amyloid-related organ response [ Time Frame: 12 weeks ]
  Amyloid-related organ response will be evaluated on the basis of the accepted criteria per consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis, in patients who completed phase 1b.
• Estimated mean area under the curve (AUC) for Ch mAb 11-1F4 [ Time Frame: Phase 1a: 1, 2, 24 hours post start of infusion; then post-infusion week 1, 2, 3, 4, 8. Phase 1b: pretreatment, 1, 2, 24 hours post start of infusion; then post-infusion week 5, 8, 12. ]
  This is designed to determine the pharmacokinetics of Ch mAb 11-1F4 when given as a single intravenous (i.v.) infusion (phase 1a) or as a series of four weekly intravenous infusions (phase 1b).
• Number of participants with adverse events [ Time Frame: 2 years approximately ]
  This to obtain additional safety data of Ch mAb 11-1F4 when given as a single intravenous infusion (phase 1a) or as a series of four weekly intravenous infusions (phase 1b) by obtaining adverse event information for all subjects during active follow-up visits.

Original Secondary Outcome:

• Reduction in amyloid burden, via 24 hour urine protein excretion, alkaline phosphatase levels, liver size, neuropathy grade levels, and natriuretic peptides (NT-proBNP) or Brain natriuretic peptide (BNP) levels or New York Heart Association class levels. [ Time Frame: 12 weeks ]
  NT-proBNP or Brain natriuretic peptide (BNP) response (greater than 30 percent and greater than 300 ng/L decrease in patients with baseline NT-proBNP greater than or equal to 650 ng/L or New York Heart Association (NYHA) class response (greater than 2 class decrease in subjects with baseline NYHA class 3 or 4).
• Area under the curve (AUC) for Ch mAb 11-1F4 when given as a single intravenous (i.v.) infusion (phase 1a) or as a series of four weekly intravenous infusions (phase 1b). [ Time Frame: 1, 2, and 18 hours post infusion. Subsequent timepoints will be done weekly for four weeks and once at Week 8. In Phase 1b, an additional measurement will be taken at week 12, post-infusion ]
• Number of Participants with Adverse Events. [ Time Frame: 2 years (approximately) ]
  Obtain additional safety data of Ch mAb 11-1F4 when given as a single intravenous (i.v.) infusion (phase 1a) or as a series of four weekly intravenous infusions (phase 1b) by obtaining adverse event information for all subjects during active follow-up visits.

Information By: Columbia University

Dates:
Date Received: September 15, 2014
Date Started: September 2014
Date Completion: December 2017
Last Updated: May 1, 2017
Last Verified: January 2017