Phase 3 Study on Efficacy and Safety of Human Normal Immunoglobulin for Infection Prophylaxis in Multiple Myeloma Patients on Teclistamab Therapy
- Trial ID
- 2024-518420-80-00
- Protocol
- TAK-339-3001
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to assess the **efficacy** of Intravenous Gammagard Liquid (Immune Globulin Infusion, 10%) for primary infection prophylaxis compared with secondary infection prophylaxis in adult subjects with multiple myeloma receiving B-cell maturation antigen-directed bispecific antibody therapy. This is clinically relevant as it aims to determine the effectiveness of the treatment in preventing infections, which is crucial for patients with multiple myeloma who are at increased risk due to their compromised immune systems.
Secondary objectives include:
- Assessing the impact of IGI, 10% treatment on all infections and infection-related outcomes.
- Evaluating the safety and tolerability of IGI, 10% for infection prophylaxis.
- Assessing the impact of IGI, 10% treatment on the frequency and duration of hospitalization due to infection.
Participants
The clinical trial involves a total of **40 participants** who are being studied for primary infection prophylaxis in the context of **secondary immunodeficiency** associated with **multiple myeloma**. The study population includes both male and female subjects, with an age range of 18 years and older. Participants were selected based on a documented diagnosis of multiple myeloma, and they must have recently started treatment with teclistamab within the first 8 weeks of their planned treatment schedule. The trial includes individuals who are considered a vulnerable population. Participants are required to provide informed consent and adhere to specific contraceptive measures if applicable. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status or specific lifestyle habits of the participants.
Plans and Procedures
The clinical trial is designed as a **randomized**, controlled, open-label, group-sequential, Phase 3 study. The primary objective is to assess the efficacy of intravenous gammagard liquid (immune globulin infusion, 10%) for primary infection prophylaxis compared to secondary infection prophylaxis in adult subjects with multiple myeloma receiving B-cell maturation antigen-directed bispecific antibody therapy. The trial is expected to commence recruitment on September 1, 2025, and conclude by October 16, 2028, with an estimated duration of 12 months for each participant's involvement.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a documented diagnosis of multiple myeloma and recent initiation of **teclistamab** treatment. Following the screening, participants will be randomized into treatment groups. The trial will include regular follow-up visits to monitor the occurrence of serious infections, the annualized rate of days on antibiotics, and the annualized rate of bacterial infections. The end-of-study visit will assess the primary endpoint, which is the time to the first serious infection.
Participant involvement is expected to last for the duration of the 12-month observational period. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, withdrawal of consent, or non-compliance with study procedures. The trial will utilize **KIOVIG** 100 mg/ml solution for infusion, administered via intravenous infusion, and **TECVAYLI** solutions for injection, administered subcutaneously, as part of the investigational regimen. The study aims to provide valuable insights into the prophylactic use of immune globulin in preventing infections in this patient population.
Treatment
The clinical trial involves the administration of **TECVAYLI** (teclistamab) in two different formulations. The first formulation is TECVAYLI 10 mg/mL solution for injection, which is administered via **subcutaneous use**. The pharmaceutical form is a solution for injection, and the maximum daily dose is 1.5 mg/kg, with a total maximum dose of 91 mg/kg over a treatment period of 14 days. This formulation has been modified for clinical trial use, featuring an extended shelf life and specific clinical trial labeling and secondary packaging compared to the commercial product.
The second formulation of TECVAYLI is a 90 mg/mL solution for injection, also administered subcutaneously. Similar to the 10 mg/mL formulation, the maximum daily dose is 1.5 mg/kg, with a total maximum dose of 91 mg/kg over a 14-day treatment period. This formulation differs in the number of significant figures defining vial strength (150 mg versus 153 mg per 1.7 mL) and also includes extended shelf life and specific clinical trial labeling and secondary packaging.
In addition to the experimental medications, the study includes the use of **KIOVIG** (human normal immunoglobulin) as a non-experimental treatment. KIOVIG is provided as a 100 mg/mL solution for infusion, administered via **intravenous infusion**. The maximum daily dose is 1000 mg/kg, with a total maximum dose of 17000 mg/kg over a treatment period of 12 days. This product has been adapted for clinical trial use with alternate storage conditions, longer shelf life, and specific clinical trial labeling and secondary packaging.
Efficacy
The efficacy of the investigational treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the time to the first serious infection, which will be measured to evaluate the effectiveness of the treatment in preventing serious infections in patients with multiple myeloma receiving B-cell maturation antigen×CD3–directed bispecific antibody therapy. Secondary endpoints include the occurrence of at least one serious infection during the 12-month observational period, the annualized rate of days on antibiotics for the treatment of bacterial infections, and the annualized rate of bacterial infections.
Data collection for these endpoints will be conducted throughout the trial duration, with specific timepoints and methods for measurement not explicitly detailed. The trial is designed as a multicenter, randomized, controlled, open-label, group-sequential, Phase 3 study. The investigational product, **Intravenous Gammagard Liquid (Immune Globulin Infusion, 10%)**, will be administered to assess its efficacy for primary infection prophylaxis compared to secondary infection prophylaxis. The trial is expected to conclude by October 16, 2028, with recruitment starting on September 1, 2025.
Inclusion and Exclusion Criteria
Inclusion Criteria
- The subject must have a documented diagnosis of MM according to the guidelines by the IMWG before enrollment.
- Subjects who recently started teclistamab within the first 8 weeks of their planned treatment schedule and are planned to receive teclistamab for the next 12 months.
- The subject has provided informed consent (ie, in writing, documented via a signed and dated ICF) and any required privacy authorization before the initiation of any study procedures.
- The subject is at least 18 years of age at the time of signing the ICF.
- If a person of childbearing potential engages in sexual relations that carry risk of pregnancy, they agree to the following for the period from screening until 30 days after the last dose of study drug: • To use a highly effective contraceptive method. • To avoid donating ova.
Exclusion Criteria
- The subject has not achieved at least a minimal response to teclistamab within 8 weeks during the screening period.
- The subject has a current serious infection or >1 serious infection in the past 3 months before screening.
- The subject has a documented polyclonal IgG level <150 mg/dL at the most recent assessment before teclistamab initiation (within 4 weeks) as assessed by the investigator according to the site’s standard practice.
- The subject is currently receiving immunoglobulin products or has received immunoglobulin products within 16 weeks before screening.
- The subject has received a hyperimmune or specialty high-titer immunoglobulin product (eg, cytomegalovirus immune globulin, varicella-zoster immune globulin, hepatitis B immune globulin) within 30 days before screening.
- The subject has received live viral vaccines within 30 days before screening.
- The subject has an Eastern Cooperative Oncology Group performance status score of >2.
- The subject has an active viral or bacterial infection or symptoms/signs of such an infection requiring treatment with anti-infectives within 1 week before enrollment.
- The subject has received other BCMA×CD3–directed BsAb therapy any time before screening.
- The subject is scheduled to undergo plasmapheresis during the course of study or has undergone plasmapheresis in the last 16 weeks before screening.
- The subject may be excluded from the study if, in the opinion of the investigator, the subject is at high risk for symptomatic hyperviscosity syndrome.
- The subject has major surgery scheduled during the study, or the subject has not fully recovered from a recent major surgery (as judged by the investigator) during screening (subjects with planned surgical procedures to be conducted under local anesthesia may participate).
- The subject has an active secondary (non-MM) malignancy or other medical condition with life‑expectancy of <2 years.
- The subject has a known history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) after IVIG and/or immune serum globulin infusions.
- The subject has a known history or current diagnosis of thromboembolic episodes such as deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, transient ischemic attack, peripheral artery disease within 6 months before screening.
- The subject has moderate to severe renal dysfunction based on an estimated glomerular filtration rate ≤30 mL/min/1.73 m2, as defined by Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for the Management of Glomerular Diseases, 2021 at the time of screening.
- The subject has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen, PCR for hepatitis C virus, PCR for HIV Type 1 and Type 2. Cured subjects with a history of hepatitis C infection who have a negative PCR test at screening are eligible.
- The subject has a documented diagnosis of a form of PID involving a defect in antibody formation and requiring IgG replacement, as defined according to the International Union of Immunological Societies Committee.
- The subject has a persistent serum aspartate aminotransferase and alanine aminotransferase >3.0 times the upper limit of normal at screening (may be repeated once to determine if it is persistent).
- The subject has an immunoglobulin A (IgA) deficiency (<0.07 g/L) with antibodies to IgA and a history of hypersensitivity reaction to IVIG.
- Subjects with a known systemic hypersensitivity to any of the excipients of IGI, 10% in accordance with the investigator’s brochure/package insert/Summary of Product Characteristics.
- Known substance abuse including opiates, psychostimulant agents, or other illicit drugs with the exception of cannabinoids within 12 months of screening.
- The subject has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site, at the discretion of the investigator (may be repeated once to determine if it has resolved).
- The subject has a medical condition, laboratory finding, or physical examination finding that precludes participation or with clinical evidence of any significant acute or chronic disease that, in the opinion of the investigator, may interfere with the successful completion of the study or place the subject at undue medical risk.
- The subject is receiving immunosuppressive treatment (other than for MM or corticosteroids) at screening or plans to receive immunosuppressive treatment after study enrollment.
- The subject is not willing and able to comply with the protocol requirements.
- The subject has participated or is scheduled to participate in another clinical study involving an IP or investigational device within 30 days before screening and during the course of the study.
- The subject is a family member or employee of the investigator or the investigator’s site staff.
- The subject is pregnant or has a positive pregnancy test or is lactating at the time of screening or enrollment.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Austria | Recruiting | 01 Sept 2025 | 9 |
 Czechia | Recruiting | 01 Sept 2025 | 27 |
 Denmark | Recruiting | 01 Sept 2025 | 8 |
 Germany | Not Yet Recruiting | 01 Sept 2025 | 13 |
 Greece | Recruiting | 01 Sept 2025 | 12 |
 Hungary | Recruiting | 01 Sept 2025 | 12 |
 Italy | Recruiting | 01 Sept 2025 | 18 |
 The Netherlands | Recruiting | 01 Sept 2025 | — |
 Norway | Recruiting | 01 Sept 2025 | 9 |
 Poland | Recruiting | 01 Sept 2025 | 3 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
KIOVIG 100 mg/ml solution for infusion | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1000 | 12 | PRD7734926 |
TECVAYLI 90 mg/mL solution for injection | Other | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 1 | PRD9891553 |
TECVAYLI 10 mg/mL solution for injection | Other | SOLUTION FOR INJECTION | SUBCUTANEOUS USE | 0 | 1 | PRD9891549 |
KIOVIG 100 mg/ml solution for infusion | Test | SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 1000 | 12 | PRD7734927 |