A Study of Subcutaneous Delivery of JNJ-54767414 (Daratumumab) in Japanese Participants With Relapsed or Refractory Multiple Myeloma

NCT03242889 | Completed Phase 1

• 2 other identifiers: CR10833754767414MMY1008
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the tolerability and safety of subcutaneous (SC) delivery of co-formulated daratumumab and rHuPH20 preparation (DARA SC) in Japanese participants with relapsed or refractory multiple myeloma (MM).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events Including Dose Limiting Toxicity

  An adverse event (AE) is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.

  Up to 30 days after last study drug dose (approximately up to 1 year)

Secondary Outcomes (6)

• Maximum Observed Concentration (Cmax) of Daratumumab

  Up to 8 weeks after the last dose of study drug (approximately up to 1 year)

• Maximum Serum Trough Concentration (Ctrough) of Daratumumab

  At Cycle 3 Day 1 predose concentration

• Serum Concentration of Daratumumab and Recombinant Human Hyaluronidase (rHuPH20) (Plasma) Antibodies

  Up to 8 weeks after the last dose of study drug (approximately up to 1 year)

• Overall Response Rate

  Approximately up to 1 year

• Duration of Response (DOR)

  First documentation of confirmed PR or better to the date of first documented progressive disease (PD), or date of death due to PD, whichever occurs first (approximately up to 1 year)

Study Arms (1)

DARA SC

EXPERIMENTAL

Participants will receive DARA SC (daratumumab 1800 milligram \[mg\] with Recombinant Human Hyaluronidase \[rHuPH20\] 30,000 units \[U\] that is 2000 U/milliliter \[U/mL\]) subcutaneous (SC) injection once weekly for the first 8 weeks in Cycles 1 and 2 (Days 1, 8, 15, and 22 of each week), every 2 weeks in Cycles 3 to 6 (Days 1 and 15) for the following 16 weeks and then every 4 weeks (from Cycle 7 \[Day 1\]) in subsequent cycles until disease progression, unacceptable toxicity, or any other reason for discontinuation. Each cycle is 28 days in duration.

Drug: DARA SC

Interventions

DARA SC DRUG

Participants will receive 1800 mg daratumumab with 30,000 U (2000 U/mL) rHuPH20 SC injection once weekly for the first 8 weeks in Cycles 1 and 2 and every 2 weeks in Cycles 3 to 6 for 16 weeks and then every 4 weeks in subsequent cycles until disease progression, unacceptable toxicity, or any other reason for discontinuation.

DARA SC

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant proven to have Multiple Myeloma (MM) according to the International Myeloma Working Group (IMWG) diagnostic criteria
• Participant must have measurable, secretory disease as defined by any of the following:
• Immunoglobulin (Ig) G MM: serum M-protein level greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) or urine M-protein level \>= 200 milligram (mg)/24 hours; or
• IgA, IgD, IgE MM: serum M-protein level \>= 0.5 g/dL or urine M-protein level \>= 200 mg/24 hours; or
• Light chain MM, for participants without measurable disease in the serum or urine: serum Ig free light chains (FLC) \>= 10 mg/dL and abnormal serum Ig kappa lambda FLC ratio
• Participant must have received \>= 2 prior lines of antimyeloma therapy without further established treatment option
• Participant must have relapsed or refractory disease
• Participant must have an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• The Participant must meet the following criteria of clinical laboratory test results during screening phase:
• hemoglobin \>=7.5 g/dL (\>=5 millimoles/liter \[mmol/L\]) (without prior Red Blood Cells (RBC) transfusion within 7 days before the laboratory test;
• absolute neutrophil count (ANC) \>=1.0\*10\^9/L (without granulocyte colony stimulating factor support in the 7 days prior the laboratory test);
• platelet count \>=75\*10\^9/L for participants in whom less than (\<)50.0 percent (%) of bone marrow nucleated cells are plasma cells; otherwise platelet count \>=50\*10\^9/L (without transfusion support in the 7 days prior to the laboratory test);
• aspartate aminotransferase (AST) less than or equal to (\<=)3.0 times upper limit of normal (ULN);
• alanine aminotransferase (ALT) \<=3.0 times ULN;
• creatinine clearance \>20 mL/minute/1.73 m\^2;

You may not qualify if:

• Participant has received daratumumab or other anti cluster of differentiation (CD)38 therapies previously
• Participant has received antimyeloma treatment within 2 weeks before Cycle 1 Day 1
• Participant has received autologous stem cell transplantation (ASCT) within 12 weeks before Cycle 1 Day 1, or the participant has previously received an allogenic stem cell transplant (regardless of timing)
• Participant has received a cumulative dose of corticosteroids equivalent or more than the equivalent of 140 mg of prednisolone within the 2-week period before Cycle 1 Day 1
• Participant has a history of malignancy (other than MM) within 3 years before Cycle 1 Day 1 (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix or breast, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)

Sponsors & Collaborators

• Janssen Pharmaceutical K.K.: lead

Study Sites (5)

National Hospital Organization Shibukawa Medical Center

Gunma, 377-0280, Japan

Location

Nagoya City University Hospital

Nagoya, 467-8602, Japan

Location

Ogaki Municipal Hospital

Ohgaki, 503-8502, Japan

Location

Osaka University Hospital

Osaka, 565-0871, Japan

Location

Japanese Red Cross Medical Center

Shibuya City, 150-8935, Japan

Location

Related Publications (2)

• Li X, Dosne AG, Perez Ruixo C, Perez Ruixo JJ. Pharmacodynamic-Mediated Drug Disposition (PDMDD) Model of Daratumumab Monotherapy in Patients with Multiple Myeloma. Clin Pharmacokinet. 2023 May;62(5):761-777. doi: 10.1007/s40262-023-01232-8. Epub 2023 Apr 6.

  PMID: 37022569 DERIVED

• Shibayama H, Matsumoto M, Kosugi H, Shibayama K, Yamazaki H, Iida S. Subcutaneous delivery of daratumumab in Japanese patients with relapsed/refractory multiple myeloma. Int J Hematol. 2021 Jan;113(1):112-121. doi: 10.1007/s12185-020-02985-9. Epub 2020 Sep 11.

  PMID: 32915384 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Janssen Pharmaceutical K.K., Japan Clinical Trial

  Janssen Pharmaceutical K.K.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2017
• First Posted: August 8, 2017
• Study Start: August 10, 2017
• Primary Completion: November 1, 2017
• Study Completion: February 10, 2023
• Last Updated: April 14, 2023

Record last verified: 2023-04

Locations

JP (5)