RAIN: Renal AL Amyloid Involvement and NEOD001

• Sponsor: Tufts Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03168906
• Collaborator: (none)
• Enrollment: 12
• Locations: 9
• Arms: 2
• Actual Duration (Months): 19.1
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm, parallel-group efficacy and safety study of NEOD001 as a single agent administered intravenously in adults with AL amyloidosis who have a maintained hematologic response to their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell transplant [ASCT]) and have persistent renal dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Amyloidosis	Drug: NEOD001; Drug: Placebo	Phase 2

Detailed Description

This is a multicenter, Phase 2b, randomized, double-blind, placebo-controlled, two-arm, parallel-group efficacy and safety study of NEOD001 as a single agent administered intravenously in adults with AL amyloidosis who have a maintained hematologic response to their most recent treatment for AL amyloidosis (e.g., chemotherapy, autologous stem cell transplant [SCT]) and have persistent renal dysfunction. Subject screening will occur during the 28 days prior to the first administration of study drug (i.e. month 1 day 1). If screening assessments are completed and all eligibility requirements are met, the subject will be enrolled. 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 may receive up to 12 infusions of study drug. Subjects who discontinue study drug before the initial End of Study (EOS) visit should have an Early Treatment Discontinuation (ETD) Visit 30 (±5) days after their final administration of study drug. After completing 12 months of treatment and the confirmatory EOS visit, a subject may enter an open-label extension (OLE) study, during which subjects will receive active treatment with NEOD001 for 12 months and may receive concurrent chemotherapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The RAIN Study, a Multicenter Randomized Double-blind Phase 2b Study of NEOD001 in Previously Treated Subjects With Systemic Light-chain (AL) Amyloidosis and Persistent Renal Involvement
• Actual Study Start Date: Jul 5, 2017
• Actual Primary Completion Date: Apr 23, 2018
• Actual Study Completion Date: Feb 6, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NEOD001 Study Drug given IV every 28 days at 24mg/kg	Drug: NEOD001; NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates
Placebo Comparator: Placebo Placebo	Drug: Placebo; Saline bag

Outcome Measures

Primary Outcome Measures

1. Confirmed Renal Response After Treatment With NEOD001 [Baseline to 13 Months]

   A renal response is a ≥ 30% reduction in proteinuria in the absence of a ≥ 25% decrease in eGFR. A confirmed renal response is one that has been documented as present one month after 12 monthly treatments.

Secondary Outcome Measures

1. Measured GFR at Study Entry [Baseline]

   The aim of this study is to assess the performance of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine in comparison to iothalamate clearance measured in AL amyloidosis patients. Iothalamate will be given subcutaneously. Urine and plasma samples will then be obtained. All laboratory tests for samples obtained for GFR measurement will be performed at Mayo Clinic Rochester. Quantification of iothalamate in urine and plasma will be performed using a tandem mass spectrometric method.

2. Time to CKD 4 or 5 [Baseline to 13 Months]

   Months to Chronic Kidney Disease level 4 or 5

3. Time to eGFR ≤ 15 or Dialysis [Baseline to 13 Months]

   Months to estimated Glomerular Filtration Rate ≤ 15 or dialysis

4. Time to Doubling of Creatinine [Baseline to 13 Months]

   Months to doubling of serum creatinine

5. Time to ≥ 40% Reduction in eGFR [Baseline to 13 Months]

   Months to ≥ 40% reduction in estimated glomerular filtration rate

6. Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments. [Baseline to 26 months]

   A renal response is a ≥ 30% decrease in proteinuria or drop of proteinuria below 0.5 g/24h in the absence of renal progression.

7. All Cause of Mortality at 26 Months [Baseline to 26 months]

   Death at 26 months from Baseline due to any cause

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years of age or older

2. Biopsy-proven diagnosis of AL amyloidosis by immunohistochemistry or mass spectroscopy of a tissue biopsy excluding bone marrow

3. Screening renal biopsy for RAIN confirming AL amyloidosis as exclusive or dominant cause of renal damage

4. Persistent renal involvement from diagnosis with proteinuria (predominantly albumin) > 500mg/day in a 24-hour urine collection

5. CKD 1 to 3 (eGFR > 30)

6. ≥1 prior systemic hematologic therapy for a free light chain (FLC) producing hematologic malignancy underlying the initial diagnosis of AL amyloidosis with at least a partial FLC response (PR, VGPR, CR) to treatment deemed stable and not requiring further treatment

7. ECOG Performance Status ≤ 2

8. Clinical laboratory values:

9. Absolute neutrophil count > 1000/μL

10. Platelet count > 75,000/μL

11. Total bilirubin ≤ 1.5X ULN

12. Alkaline phosphatase ≤ 5X ULN

13. NT-proBNP < 1800 pg/mL

14. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care

Exclusion Criteria:

1. Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis

2. Female patients who are lactating, breastfeeding, or pregnant

3. Patients who have not been treated or who have received chemotherapy within 6 months, or SCT within 12 months, for the light-chain producing hematologic disease causing AL amyloidosis, at the time of the first dose of NEOD001 (month 1 day 1)

4. Patients who at initial diagnosis or later met the International Myeloma Working Group (IMWG) definition of active multiple myeloma requiring therapy (Appendix 3)

5. Patients whose screening renal biopsies for RAIN show dominant causes of renal damage not related to AL amyloidosis

6. Medically documented cardiac syncope, uncompensated congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive atrial or ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically significant uncompensated autonomic insufficiency

7. Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens

8. Ongoing or active infection, known HIV positive, known to be hepatitis B surface antigen-positive or has known or suspected active hepatitis C infection.

9. Psychiatric illness/social situations that would limit compliance with study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic- Arizona	Scottsdale	Arizona	United States	85259
2	University of California San Francisco	San Francisco	California	United States	94143
3	Mayo Clinic- Florida	Jacksonville	Florida	United States	32224
4	Tufts Medical Center	Boston	Massachusetts	United States	02111
5	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
6	Mayo Clinic- Minnesota	Rochester	Minnesota	United States	55905
7	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
8	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
9	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Tufts Medical Center

Investigators

• Study Chair: Raymond Comenzo, MD, Tufts Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 13, 2017

More Information

Publications

None provided.

• Responsible Party: Tufts Medical Center
• ClinicalTrials.gov Identifier: NCT03168906
• Other Study ID Numbers: NEOD001-RAIN
• First Posted: May 30, 2017
• Last Update Posted: Sep 9, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Tufts Medical Center: Amyloidosis; NEOD001; RAIN
• Additional relevant MeSH terms: Amyloidosis

Study Results

Participant Flow

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo Placebo: Saline bag
Period Title: Overall Study
STARTED	6	6
COMPLETED	0	0
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	NEOD001	Placebo	Total
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo Placebo: Saline bag	Total of all reporting groups
Overall Participants	6	6	12
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	4 66.7%	5 83.3%	9 75%
>=65 years	2 33.3%	1 16.7%	3 25%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60	54.5	57.5
Sex: Female, Male (Count of Participants)
Female	2 33.3%	2 33.3%	4 33.3%
Male	4 66.7%	4 66.7%	8 66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 16.7%	1 16.7%	2 16.7%
White	5 83.3%	5 83.3%	10 83.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Confirmed Renal Response After Treatment With NEOD001
Description	A renal response is a ≥ 30% reduction in proteinuria in the absence of a ≥ 25% decrease in eGFR. A confirmed renal response is one that has been documented as present one month after 12 monthly treatments.
Time Frame	Baseline to 13 Months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo Placebo: Saline bag
Measure Participants	0	0

2. Secondary Outcome

Title	Measured GFR at Study Entry
Description	The aim of this study is to assess the performance of CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine in comparison to iothalamate clearance measured in AL amyloidosis patients. Iothalamate will be given subcutaneously. Urine and plasma samples will then be obtained. All laboratory tests for samples obtained for GFR measurement will be performed at Mayo Clinic Rochester. Quantification of iothalamate in urine and plasma will be performed using a tandem mass spectrometric method.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

3. Secondary Outcome

Title	Time to CKD 4 or 5
Description	Months to Chronic Kidney Disease level 4 or 5
Time Frame	Baseline to 13 Months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

4. Secondary Outcome

Title	Time to eGFR ≤ 15 or Dialysis
Description	Months to estimated Glomerular Filtration Rate ≤ 15 or dialysis
Time Frame	Baseline to 13 Months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

5. Secondary Outcome

Title	Time to Doubling of Creatinine
Description	Months to doubling of serum creatinine
Time Frame	Baseline to 13 Months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

6. Secondary Outcome

Title	Time to ≥ 40% Reduction in eGFR
Description	Months to ≥ 40% reduction in estimated glomerular filtration rate
Time Frame	Baseline to 13 Months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

7. Secondary Outcome

Title	Renal Response in Patients With Maintained Hematologic Responses After 24 Monthly Treatments.
Description	A renal response is a ≥ 30% decrease in proteinuria or drop of proteinuria below 0.5 g/24h in the absence of renal progression.
Time Frame	Baseline to 26 months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

8. Secondary Outcome

Title	All Cause of Mortality at 26 Months
Description	Death at 26 months from Baseline due to any cause
Time Frame	Baseline to 26 months

Outcome Measure Data

Analysis Population Description

Trial was closed prior to completion, therefore data were not collected.

Arm/Group Title	NEOD001	Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates	Placebo
Measure Participants	0	0

Adverse Events

Time Frame	1 month
Arm/Group Title	NEOD001		Placebo
Arm/Group Description	Study Drug given IV every 28 days at 24mg/kg NEOD001: NEOD001 is a monoclonal antibody directed at soluble and insoluble light chain aggregates		Placebo Placebo: Saline bag
All Cause Mortality
	NEOD001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	NEOD001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	NEOD001		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/6 (50%)		3/6 (50%)
Gastrointestinal disorders
Nausea	1/6 (16.7%)	1	0/6 (0%)	0
Constipation	0/6 (0%)	0	1/6 (16.7%)	1
General disorders
Chest pain	1/6 (16.7%)	1	0/6 (0%)	0
Fatigue	2/6 (33.3%)	2	0/6 (0%)	0
Upper and lower extremity swelling	0/6 (0%)	0	1/6 (16.7%)	1
Injury, poisoning and procedural complications
Concussion	1/6 (16.7%)	1	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Right hip pain	1/6 (16.7%)	1	0/6 (0%)	0
Nervous system disorders
Left arm pain	1/6 (16.7%)	1	0/6 (0%)	0
Renal and urinary disorders
Dysuria	1/6 (16.7%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Coughing spells	0/6 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.