SUMMARY  

• There are no systematically collected data to support use of DARZALEX FASPRO with administration routes alternative to subcutaneous (SC) injection. Janssen cannot recommend any practices, procedures, or dosing modifications that deviate from product labeling and are not approved by regulatory agencies.
• Janssen recommends reporting all medication errors and/or adverse events to local regulatory authorities and/or Janssen directly.
• In the event of a medication error of administration of DARZALEX FASPRO as intravenous (IV) injection/infusion, there are no data or recommendations regarding re-administration with another dose.

CLINICAL DATA

Printz et al (2020)¹ investigated the safety profile, pharmacokinetics (PK), and pharmacodynamics (PD) of hyaluronidase (hereafter referred to as rHuPH20) administered IV to understand the potential impact of inadvertent IV injection of rHuPH20. Correlation between these results and safety and efficacy of inadvertent administration of daratumumab and hyaluronidase IV has not been established.

Study Design/Methods

• Phase 1, open-label, single-center study
• Healthy volunteers (n=24) received 5 mL IV infusion of 10,000 U (n=12) or 30,000 U (n=12) rHuPH20 over 5 minutes.
• Mean age: 36.5 years (range, 24-60); male: 58.3% (n=14)
• Key exclusion criteria: known allergy to hyaluronidase, prior exposure to hyaluronidase, hypersensitivity to heparin or contraindication to heparin lock
• Primary endpoint: safety and tolerability of rHuPH20 administered intravenously.
• Secondary endpoints: PK profile
• Exploratory endpoint: PD profile of plasma hyaluronan (HA)
• Blood samples for plasma analysis were collected 30 and 5 minutes before starting IV infusion, and at 1, 3, 4.5, 6, 8, 10, 12, 15, 17, 20, 25, 30, and 45 minutes, and 1, 2, 4, and 24 hours after initiation of infusion. Samples were also collected on Day 2, 7, and at follow-up visits where applicable.
• Plasma concentrations of rHuPH20 were analyzed using an enzymatic assay and an immunoreactive assay.

Results

Safety

• No deaths or discontinuations were reported due to adverse events.
• No clinically significant laboratory abnormalities were observed.
• No serious adverse events were reported in either treatment group.
• Grade 1 adverse events (n=2) were reported:
  • 10,000 U group: catheter site pain (n=1)
  • 30,000 U group: hypotension (n=1)
    • Hypotension occurred in a 42-year-old female with a body mass index of 22.9. There was no notable medical history and no concomitant medication use. Blood pressure (BP) at screening was 106/65 and 95/58 mmHg predose. Four hours after administration of 30,000 U rHuPH20 over 5 minutes, BP was recorded as 76/48 mmHg. Approximately 1 hour later, BP was 92/61. No action was taken for the event.  
  • Both adverse events were considered transient and unrelated to study treatment by the investigator.

PK/PD

• Following a single 5 minute IV infusion of rHuPH20, there was a rapid increase in plasma rHuPH20 concentration, peaking on average at 6 minutes post-initiation of infusion and quickly declining within 2 hours.
• T_1/2 using enzymatic data were 3.7 and 5.6 minutes respectively for the 10,000 U and 30,000 U doses vs 6.6 and 10.4 minutes for immunoreactive-based methods.
• Median T_max was similar with both PK assays.
• Median plasma HA T_max was reached 60-90 minutes after dosing. Plasma HA concentrations returned to baseline within 1 week of dosing in both arms.  

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on
14 November 2024.