Immunoglobulin for Primary Immunodeficiency

(KIDCARES10 Trial)

Recruiting at 11 trial locations

Overseen By Nicola Rovai

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Kedrion S.p.A.

Must be taking: IVIg

Must not be taking: Steroids, Immunosuppressives

Disqualifiers: AIDS, Hepatitis B/C, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 21

Duration: 48 weeks

30 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking steroids at a daily dosage of 0.15 mg/kg/day or more of prednisone (a type of steroid) and other immunosuppressive drugs at least 30 days before starting the trial. Other IVIg treatments are also not allowed after signing the consent form.

What data supports the effectiveness of the drug Kedrion IVIG 10% for primary immunodeficiency?

Research shows that intravenous immunoglobulin (IVIG) treatments, like Kedrion IVIG 5%, are effective and safe for children with primary immunodeficiency, reducing severe infections. Additionally, a study on a 10% IVIG formulation found it effective in patients with primary immunodeficiency, suggesting similar benefits for Kedrion IVIG 10%. ^{1 2 3 4 5}

Is immunoglobulin treatment generally safe for humans?

Immunoglobulin treatments, like Kedrion IVIG 10% and others, are generally considered safe, but they can cause side effects in some people. Serious side effects have been reported, affecting the kidneys, heart, skin, and blood, and the risk can depend on factors like age, health conditions, and the specific product used. It's important for doctors to carefully consider these risks and benefits before prescribing. ^{6 7 8 9 10}

What makes Kedrion IVIG 10% unique for treating primary immunodeficiency?

Kedrion IVIG 10% is a concentrated intravenous immunoglobulin (IVIG) treatment specifically designed for primary immunodeficiency, offering a higher concentration compared to some other IVIG options like Kedrion 5%. This allows for potentially fewer infusions and a more convenient treatment schedule for patients. ^{1 2 11 12 13}

What is the purpose of this trial?

The purpose of this study is to assess efficacy, safety and pharmacokinetics of Kedrion Immunoglobulin 10% (KIg10) in pediatric patients with Primary Immunodeficiency Disease (PID).

Research Team

Chiara Azzari

Principal Investigator

Azienda Ospedaliero-Universitaria Ospedale Pediatrico Meyer - Italy

Eligibility Criteria

This trial is for children and teens aged 2 to under 18 with Primary Immunodeficiency Disease (PID) who need IVIg treatment. They must have a confirmed diagnosis, documented low antibody levels, and have been on stable IVIg therapy before joining. Participants also need consent from parents or guardians and agree to follow the study rules.

Inclusion Criteria

I weigh at least 15 kg.

Written informed consent/assent obtained from the patient and his/her parent(s) or legally acceptable representative indicating understanding of the study purpose and procedures

Documented agammaglobulinemia or hypogammaglobulinemia

Exclusion Criteria

Using an implanted venous access device

I have epilepsy that doesn't respond to medication or I often have migraines.

I have a new diagnosis of PID and haven't started IgG therapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusion of Kedrion IVIG 10% at a dose of 200 to 800 mg/kg body weight every 21 or 28 days

48 weeks

Infusions every 21 or 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Kedrion IVIG 10%

Trial Overview The KIDCARES10 study is testing the effectiveness, safety, and how the body processes Kedrion Immunoglobulin 10% (KIg10), an intravenous treatment for kids with PID. The trial involves regular infusions of this medication over time.

Participant Groups

Group I: Experimental: Kedrion IVIG 10% Experimental Treatment 1 Intervention

Participants will receive intravenous infusion of Kedrion IVIG 10% at a dose of 200 to 800 milligram per kilogram (mg/kg) body weight every 21 or 28 days for period of 48 weeks.

Kedrion IVIG 10% is already approved in United States, European Union for the following indications:

Approved in United States as Kedrion IVIG 10% for:

• Primary Immunodeficiency Disease (PID)
• Chronic Immune Thrombocytopenic Purpura (ITP)
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Approved in European Union as Kedrion IVIG 10% for:

• Primary Immunodeficiency Disease (PID)
• Chronic Immune Thrombocytopenic Purpura (ITP)
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Who Is Running the Clinical Trial?

Kedrion S.p.A.

Lead Sponsor

Trials

8

Recruited

330+

Findings from Research

Kedrion 5% intravenous immunoglobulin G (IVIg) treatment is both effective and safe for children and adolescents with primary immunodeficiencies, helping to reduce their susceptibility to severe infections.

The study included a long follow-up period totaling 71 patient-years, making it one of the few to specifically evaluate the safety and efficacy of IVIg in a pediatric population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of human intravenous immunoglobulin 5% (Ig VENA) in pediatric patients affected by primary immunodeficiency. Ricci, S., Lippi, F., Canessa, C., et al.[2021]

A study of 23 patients with primary immunodeficiencies showed that alternating between subcutaneous immunoglobulin (SCIG) and intravenous immunoglobulin (IVIG) was effective in preventing severe infections, with no hospital admissions for infections during the study period.

The use of SCIG and IVIG provided significant convenience for patients and caregivers, with 39.1% of patients temporarily switching to IVIG for reasons like vacation and administration issues, while maintaining safety with only a few documented adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous and subcutaneous immunoglobulin replacement: a two-way road. Optimizing healthcare quality in patients with primary immunodeficiencies. Soler-Palacín, P., Gasó-Gago, I., Fernández-Polo, A., et al.[2021]

Switching from intravenous immunoglobulin (IVIG) to subcutaneous immunoglobulin (SCIG) treatment in 29 patients with immunodeficiencies resulted in significantly higher serum IgG levels (from 588.9 mg/dl to 872 mg/dl) after one year, indicating effective immunoglobulin management.

Patients experienced fewer infections and less time away from school or work after switching to SCIG, along with improved quality of life scores, while no serious side effects were reported, highlighting the safety and efficacy of SCIG treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder. Sarı, G., Güven Bilgin, B., Yılmaz, E., et al.[2022]

In a study involving 63 patients with primary immunodeficiency, the investigational 10% IVIG was found to be well tolerated, with adverse events occurring in 27.7% of infusions, indicating a good safety profile.

The treatment demonstrated effectiveness with a low rate of serious bacterial infections (0.035 per person per year) and minimal missed days of work or school due to infections (2.28 days/patient/year), suggesting it is a viable option for managing PID.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of a new 10% liquid intravenous immunoglobulin (IVIG) in patients with primary immunodeficiency. Wasserman, RL., Church, JA., Stein, M., et al.[2022]

Children with primary immunodeficiency disorder reported more positive experiences ('sweetness') with subcutaneous immunoglobulin (SCIg) compared to intravenous immunoglobulin (IVIg), highlighting benefits like a sense of freedom, improved quality of life, and ease of use.

Despite some concerns ('bitterness') about self-injection responsibilities and body image issues, the overall transition to SCIg was viewed favorably, suggesting that proper training and support can enhance patient experiences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Experiences of Children with Primary Immunodeficiency Who Receive Immunoglobulin Subcutaneously Instead of Intravenously. Köse, S., Sabetsarvestani, R., Geçkil, E., et al.[2023]

While IGIV products are generally considered safe, many clinical studies have been small and may not fully capture the incidence of adverse events, which can include serious complications affecting various organ systems.

Clinicians should carefully evaluate the risks and benefits of IGIV therapy, considering factors like patient age and underlying health conditions, and should only prescribe these products for conditions with strong evidence of efficacy from well-controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks associated with the use of intravenous immunoglobulin. Pierce, LR., Jain, N.[2022]

Adverse drug reactions occur in about 10% of patients receiving immunoglobulin treatment, but most can be prevented with careful prescription, administration, and supervision.

Key preventive measures include ensuring proper hydration before and during treatment, using lower doses, and infusing at a slow rate, which can significantly reduce the risk of both serious and non-serious adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Human immunoglobulins, adverse drug reaction, prevention]. Grenouillet-Delacrea, M., Longy-Boursier, M.[2016]

In a study involving 15,958 children and adolescents, only 2.1% reported poorly tolerated vaccinations, indicating that serious adverse reactions are relatively rare.

The reported adverse reactions were consistent with existing safety information for vaccines, and the overall benefit-risk ratio of vaccinations remains positive, suggesting that vaccines are still safe and effective despite concerns about side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Suspected adverse reactions after vaccination. Results from the German Health Interview and Examination Survey for Children and Adolescents. Part I: descriptive analyses]. Poethko-Müller, C., Atzpodien, K., Schmitz, R., et al.[2016]

In a safety surveillance study of influenza vaccines during the 2017/18 season, adverse reactions (ARs) were reported by 2.9% of participants receiving the intradermal IIV3-ID vaccine, 1.4% for the standard IIV3 vaccine, and 2.1% for the quadrivalent IIV4 vaccine, indicating a generally low incidence of ARs across all vaccine types.

The most common ARs were injection-site reactions and headaches, and no significant changes in AR rates were observed compared to the previous season, suggesting consistent safety profiles for these vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced passive safety surveillance of three marketed influenza vaccines in the UK and the Republic of Ireland during the 2017/18 season. Gandhi-Banga, S., Chabanon, AL., Eymin, C., et al.[2020]

In a study of 697 children admitted to the Pediatric Intensive Care Unit (PICU), 13.1% experienced at least one adverse drug reaction (ADR), with a notably higher incidence of 22% in patients who had undergone cardiovascular surgery.

ADRs significantly increased the economic burden, raising ICU costs by 3.5 times and extending the length of stay by 3.8 times, highlighting the need for enhanced surveillance and early intervention for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and costs of adverse drug reactions in a tertiary care pediatric intensive care unit. Du, W., Tutag Lehr, V., Caverly, M., et al.[2013]

Subcutaneous immunoglobulin (SCIG) therapy effectively maintains serum IgG levels and significantly reduces the number of antibiotics and hospitalizations in patients with primary immunodeficiency (PIDD), particularly in those who are naive to immunoglobulin replacement.

SCIG is associated with fewer systemic side effects compared to intravenous immunoglobulin (IVIG), leading to an overall improvement in quality of life, although compliance remains a challenge, with 10 out of 20 patients discontinuing therapy for various reasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous immunoglobulin therapy for adult patients with primary immunodeficiency disease: Qatar experience. Thalappil, S., Khalil, S., Hassini, S., et al.[2023]

In a study involving 25 children with primary immunodeficiency, IVIG 10% demonstrated a very low rate of serious bacterial infections at 0.04 per patient-year, indicating its efficacy in preventing infections.

The treatment was found to be safe, with common side effects including abdominal pain, headache, and chills, while maintaining effective immunoglobulin G levels between infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin 10% in children with primary immunodeficiency diseases. Ochs, HD., Melamed, I., Borte, M., et al.[2019]

Kiovig, a 10% liquid immunoglobulin preparation, has been found to have similar safety and effectiveness compared to other intravenous immunoglobulin products for treating primary immunodeficiency disorders, based on a literature review.

The cost-effectiveness of Kiovig is heavily influenced by its price and associated treatment costs, highlighting the need for further comparative studies to better understand its economic impact and overall value in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of primary immunodeficiency with Kiovig: a literature review. Simoens, S.[2010]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of human intravenous immunoglobulin 5% (Ig VENA) in pediatric patients affected by primary immunodeficiency. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Intravenous and subcutaneous immunoglobulin replacement: a two-way road. Optimizing healthcare quality in patients with primary immunodeficiencies. [2021]

3. Italy pubmed.ncbi.nlm.nih.gov

Efficacy and quality of life assessment in the use of subcutaneous immunoglobulin treatment for children with primary immunodeficiency disorder. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, efficacy and pharmacokinetics of a new 10% liquid intravenous immunoglobulin (IVIG) in patients with primary immunodeficiency. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The Experiences of Children with Primary Immunodeficiency Who Receive Immunoglobulin Subcutaneously Instead of Intravenously. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Risks associated with the use of intravenous immunoglobulin. [2022]

7. France pubmed.ncbi.nlm.nih.gov

[Human immunoglobulins, adverse drug reaction, prevention]. [2016]

8. Germany pubmed.ncbi.nlm.nih.gov

[Suspected adverse reactions after vaccination. Results from the German Health Interview and Examination Survey for Children and Adolescents. Part I: descriptive analyses]. [2016]

9. United States pubmed.ncbi.nlm.nih.gov

Enhanced passive safety surveillance of three marketed influenza vaccines in the UK and the Republic of Ireland during the 2017/18 season. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Incidence and costs of adverse drug reactions in a tertiary care pediatric intensive care unit. [2013]

11. Qatar pubmed.ncbi.nlm.nih.gov

Subcutaneous immunoglobulin therapy for adult patients with primary immunodeficiency disease: Qatar experience. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Intravenous immunoglobulin 10% in children with primary immunodeficiency diseases. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Treatment of primary immunodeficiency with Kiovig: a literature review. [2010]