Daratumumab for Polyneuropathy Associated With MGUS

NCT06046287 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00005648
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn about daratumumab and hyaluronidase-fihj in patients with monoclonal gammopathy of undetermined significant (MGUS) who have been diagnosed with peripheral neuropathy suspected to be cause by paraproteinemia. The main question\[s\] it aims to answer are: • how well does this medication help improve MGUS associated peripheral neuropathy Participants will be asked be asked to get some testing done prior to starting the trial in order for us to assess your nerve damage or peripheral neuropathy. This will include blood tests, a complete neurologic examination, surveys and tests called electromyogram and nerve conduction studies. Participants that qualify for the trial will take DARZALEX FASPRO® once a week for two months, followed by every other week from months 3 to month 6.

Conditions

Peripheral Neuropathy; Monoclonal Gammopathy of Undetermined Significance

Outcome Measures

Primary Outcomes (1)

• ISS score change

  changes from baseline to 12 months in functional assessments ISS score

  12 months

Secondary Outcomes (9)

• Functional Assessment change

  3, 6, 9,12 months

• Change in nerve conduction studies (NCS)

  3, 6, 9, 12 months

• Electromyography (EMG) changes

  12 months

• Inflammatory Neuropathy Cause and Treatment (INCAT) changes

  3, 6, 9, 12 months

• Change in health-related quality of life

  3, 6, 9, and 12 months

Study Arms (1)

Daratumumab and hyaluronidase-fihj

EXPERIMENTAL

Drug: Daratumumab and hyaluronidase-fihj

Interventions

Daratumumab and hyaluronidase-fihj DRUG

subucatneous, fixed dose 1800mg combination drug product containing rHuPH20 drug substance (2000 U/mL) and daratumumab drug substance (120 mg/mL) will be administered weekly for the first 8 weeks, and then every 2 weeks from week 9 to week 24.

Also known as: Darzalex Faspro

Daratumumab and hyaluronidase-fihj

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of informed consent
• A diagnosis of chronic demyelinating neuropathy according to the European Federation of Neurological Societies/Peripheral Nerve Society guidelines for chronic inflammatory demyelinating polyneuropathy (as determined by neurologist) with concurrent diagnosis of monoclonal gammopathy of undetermined significance (MGUS) with an IgM monoclonal peak (see appendix 8)
• Peripheral neuropathy associated with anti-MAG \>7000 BTU, with EMG/NCS consistent with polyneuropathy.
• Patients will have to have disability associated with their peripheral neuropathy, with a baseline INCAT Sensory Score (ISS) score ≥4.
• They must have an ataxia score ≥2 (0 = normal, 1 = slight oscillations, 2 = marked oscillations, 3 = severe ataxia), and/or visual analog pain scale (VAS) \>4 (from 0 = no pain to 10 = maximal pain).
• Must meet MGUS diagnostic criteria as diagnosed using IMWG criteria using the following criteria (see section 1 appendix):
• Serum monoclonal protein \<30g/L
• Clonal bone marrow lymphoplasmacytic/plasma cells \<10%
• Absence of end-organ damage related to the plasma cell dyscrasia\*
• Serum calcium \>0.25 mmol/L (\>1mg/dL) higher than the upper limit of normal or \>2.75 mmol/L (\>11mg/dL)
• Renal insufficiency: creatinine clearance \<40 mL per minute or serum creatinine \>177mol/L (\>2mg/dL)
• Anemia: hemoglobin value of \>20g/L below the lowest limit of normal, or a hemoglobin value \<100g/L
• Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has \<10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 3 (see appendix)
• Adequate bone marrow function:

You may not qualify if:

• Documented active multiple myeloma, smoldering myeloma, Waldenstroms macroglobulinemia, non-IgM MGUS, plasma cell leukemia or systemic amyloid light chain amyloidosis
• Concomitant disorder felt to possibly be related to the etiology of the peripheral neuropathy: diabetes, vitamin deficiency, chronic alcohol consumption, drugs, HCV infection.\*\*
• Prior or current exposure to any of the following:
• To daratumumab and Hyaluronidase-fhj or other anti-CD-38 therapies (unless a re-treatment study)
• Exposure to an investigational drug (including investigational vaccine) or invasive investigational medical device for any indication within 4 weeks or 5 pharmacokinetic half-lives, whichever is longer.
• Chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) \< 50% of predicted normal. Note that FEV1 testing is required for participants suspected of having COPD and participants must be excluded if FEV1 is \< 50% of predicted normal.
• Moderate or severe persistent asthma within the past 2 years (see Appendix section 1), or uncontrolled asthma of any classification. Note that participants who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed to participate.
• Participant is:
• Known history of human immunodeficiency virus (HIV)
• Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\]). Subjects with resolved infection (i.e., subjects who are HBsAg negative with antibodies to total hepatitis B core antigen \[anti-HBc\] with or without the presence of hepatitis B surface antibody \[anti-HBs\]) must be screed using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of HBV vaccination, do not need to be testing for HBV DNA by PCR.
• Seropositive for hepatitis C (except in the setting of a sustained virologic response \[SVR\], defined as a viremia at least 12 weeks after completion of antiviral therapy).
• Patients who have implanted deep brain stimulators and vagal nerve stimulators.
• Clinically significant cardiac disease, including:
• Myocardial infarction within 6 months before randomization, or unstable or uncontrolled disease/condition related to or affection cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) \[refer to Appendix section 3\]
• Uncontrolled cardiac arrhythmia

Sponsors & Collaborators

• Georgetown University: lead
• Janssen, LP: collaborator

Study Sites (2)

Lombardi Comprehensive Cancer Center, Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Peripheral Nervous System Diseases; Monoclonal Gammopathy of Undetermined Significance

Interventions

daratumumab

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases; Hypergammaglobulinemia; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Kimberley Doucette, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2023
• First Posted: September 21, 2023
• Study Start: September 26, 2025
• Primary Completion: September 26, 2025
• Study Completion: September 26, 2025
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)