Newnorm for Primary Immunodeficiency

Not currently recruiting at 25 trial locations

Overseen By Patrick Murphy

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Octapharma

Must be taking: Immunoglobulin therapy

Must not be taking: Anticoagulants, Immunosuppressants, Steroids

Disqualifiers: Acute infection, Cancer, Liver dysfunction, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Newnorm for individuals with primary immunodeficiency diseases. The researchers aim to evaluate the treatment's effectiveness, how the body processes it, and its safety and side effects. It involves administering a special type of human immunoglobulin (proteins that help fight infections) under the skin. Suitable participants have received regular immunoglobulin therapy for at least 12 weeks and have a confirmed diagnosis of primary immunodeficiency. As a Phase 3 trial, this is the final step before FDA approval, providing participants an opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like systemic immunosuppressants, high-dose steroids, and some anticoagulants may not be allowed. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that Newnorm is likely to be safe for humans?

Research shows that treatments like Newnorm, administered under the skin, are usually easy for people to handle. One study found that a similar product worked well and caused only a few side effects for patients who had used similar treatments before. This suggests that people generally tolerate the treatment well, with no major safety concerns reported.

Additionally, using human immunoglobulin to treat primary immunodeficiency has been shown to improve health by reducing infections. This history of use supports the treatment's safety. Newnorm's testing in a late-stage trial indicates that earlier tests did not find any major safety problems. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for primary immunodeficiency, which often involve intravenous infusions, Newnorm is unique because it is a 20% human normal immunoglobulin specifically designed for subcutaneous infusion. This delivery method allows for easier administration and potentially fewer side effects, offering more convenience and comfort for patients. Researchers are excited about Newnorm because it could provide a more flexible and patient-friendly option, allowing individuals to manage their condition with greater ease and less disruption to their daily lives.

What evidence suggests that Newnorm might be an effective treatment for primary immunodeficiency?

Research has shown that using human immunoglobulin, such as Newnorm, can help people with primary immunodeficiency diseases live longer and experience fewer illnesses. Immunoglobulin strengthens the immune system, enhancing its ability to fight infections. Participants in this trial will receive Newnorm, a 20% subcutaneous human immunoglobulin. Although no evidence currently proves its superiority over other similar treatments, subcutaneous immunoglobulin treatments are generally considered beneficial for managing these conditions. Overall, the treatment aims to provide patients with stronger protection against infections. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people aged 2 to 75 with Primary Immunodeficiency Diseases (PID) who need immunoglobulin therapy. They must have been on stable treatment doses for at least 12 weeks and agree to protocol requirements, including blood sampling. Excluded are those with severe allergies to IgA, obesity (BMI >40), liver dysfunction, uncontrolled diabetes or hypertension, certain heart conditions, recent blood product exposure other than IgG for PID, or active infections.

Inclusion Criteria

Willingness to comply with all aspects of the protocol, including blood sampling, for the duration of the study.

My IgG levels have been above 5 g/L recently and at screening.

Freely given written informed consent from adult patients or freely given written informed consent from the patient's parent(s)/legal guardian(s) and written informed assent from paediatric or adolescent patients in accordance with the applicable regulatory requirements, before any study-specific procedure takes place.

Exclusion Criteria

Body mass index >40 kg/m2.

Known human immunodeficiency virus (HIV)-1/2, hepatitis B virus (HBV), or hepatitis C virus (HCV) infection or positive for HIV-1/2, HBV, or HCV at screening.

I have a condition like leukemia or lymphoma that weakens my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive subcutaneous human immunoglobulin (Newnorm) to evaluate pharmacokinetics, efficacy, tolerability, and safety

52 weeks

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Newnorm

Trial Overview The study is testing 'Newnorm,' a subcutaneous human immunoglobulin treatment for patients with PID. It's an open-label Phase 3 trial assessing how the body processes the drug and its effectiveness and safety across multiple centers.

How Is the Trial Designed?

Group I: Newnorm Experimental Treatment 1 Intervention

Newnorm is a 20% human normal immunoglobulin for SC infusion

Newnorm is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Newnorm for:

• Primary Immunodeficiency Diseases

Approved in United States as Human Immunoglobulin for:

• Primary Immunodeficiency Diseases
• Chronic Inflammatory Demyelinating Polyneuropathy

Approved in Canada as Human Immunoglobulin for:

• Primary Immunodeficiency Diseases

Who Is Running the Clinical Trial?

Octapharma

Lead Sponsor

Trials

86

Recruited

11,300+

Wolfgang Marguerre

Octapharma

Chief Executive Officer since 1983

MBA from INSEAD

Wolfgang Frenzel

Octapharma

Chief Medical Officer since 2010

MD from University of Vienna

Published Research Related to This Trial

Gammanorm® 16.5% (subcutaneous immunoglobulin) was found to be effective in providing protection against infections in patients with primary immunodeficiencies, with a mean dose of 28.7 g/month and only 7 out of 33 patients experiencing serious bacterial infections.

The treatment was well-tolerated, with no serious adverse events related to SCIG and only minor drug-related reactions in 2 out of 43 patients, indicating a favorable safety profile and improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety and quality of life in patients receiving subcutaneous IgG treatment: experience in Bogotá, Colombia. Ortega-López, MC., Garay, J., Pinilla, ML.[2019]

A survey of 300 patients with primary immunodeficiency disease (PID) revealed that while 76% were satisfied with their immunoglobulin treatments, their overall physical and mental well-being remained below normal health standards.

Patients expressed a strong preference for improvements in treatment, including the option for 4-weekly infusions, home administration, self-administration, shorter infusion times, and fewer needle sticks, indicating a need for more patient-centered treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving current immunoglobulin therapy for patients with primary immunodeficiency: quality of life and views on treatment. Espanol, T., Prevot, J., Drabwell, J., et al.[2022]

A study analyzing 456 serum samples from PID-free children established reliable reference intervals for IgG and IgG subclasses using Optilite® reagents, which are crucial for diagnosing primary immunodeficiency (PID) in pediatric patients.

The findings highlight the importance of using manufacturer-specific reference intervals for IgG subclass measurements, as variations in calibration can lead to differences in reported levels compared to existing literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents. Grunewald, O., Lopez, B., Brabant, S., et al.[2019]

A male patient with common variable hypogammaglobulinemia experienced a significant decline in serum IgA levels, dropping to undetectable levels over one year, while his IgG and IgM levels remained low but stable.

Despite the lack of IgA, the patient's B lymphocytes still showed some ability to secrete IgA in laboratory tests, indicating that there may be residual functionality in his immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a serologically complete IgA deficiency in a patient with common variable hypogammaglobulinemia. Smith, CI., Hammarström, L., Palmblad, J.[2006]

In a study of 262 patients with common variable immunodeficiency, severe adverse reactions to immunoglobulin therapy were rare but could occur even after long-term tolerance to treatment.

Subcutaneous immunoglobulin therapy was generally safe for patients who switched from intravenous treatment, but those with a history of severe reactions to intravenous therapy are at higher risk for adverse reactions with subcutaneous administration, necessitating careful monitoring during the transition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study on CVID patients with adverse reactions to intravenous or subcutaneous IgG administration. Quinti, I., Soresina, A., Agostini, C., et al.[2022]

In a study of 18 adults (94.4% women) with IgG subclass deficiency and subnormal IgG2 levels, a high prevalence of respiratory infections and autoimmune conditions was observed, highlighting the clinical challenges faced by these patients.

The majority of patients showed inadequate responses to the pneumococcal vaccine (PPSV23), indicating potential issues with immune protection, particularly in those with subnormal IgG2 and other immunologic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of adult patients with IgG subclass deficiency and subnormal IgG2. Barton, JC., Barton, JC., Bertoli, LF., et al.[2020]

In a study of 49 neonates with various gastrointestinal conditions, those with gastrointestinal anomalies and necrotizing enterocolitis showed a significant increase in IgA levels, indicating a potential immune response (p < 0.001).

Neonates with low anorectal anomalies and spina bifida had normal or undetectable IgA levels, suggesting that these conditions may not trigger the same immune response as gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significance of elevated IgA antibody levels in neonates with gastrointestinal conditions. Reen, DJ., Puri, P.[2019]

The FIGARO study, involving 156 patients with primary or secondary immunodeficiency diseases, demonstrated that facilitated subcutaneous immunoglobulin (fSCIG) is feasible and well-tolerated, with most patients self-administering their treatment at home.

At the 12-month follow-up, 85.8% of patients were infusing at home and 88.2% were self-administering, with a low incidence of acute severe bacterial infections (0%-9.1%), indicating effective infection control and safety across different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facilitated Subcutaneous Immunoglobulin Treatment in Patients with Immunodeficiencies: the FIGARO Study. Borte, M., Hanitsch, LG., Mahlaoui, N., et al.[2023]

A new flow cytometry-based assay was developed to detect various immunoglobulin classes and subclasses in the serum of 47 HIV-1-infected pregnant women, revealing that IgG1 was the most frequently reactive antibody class against HIV-1 proteins.

Mothers who transmitted HIV-1 to their infants had a broader distribution of antibody classes compared to non-transmitting mothers, with IgG2-gp160 being the most common antibody-antigen combination found in transmitting mothers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin class and subclass antibodies to HIV proteins in maternal serum: association with perinatal transmission. Mann, DL., Hamlin-Green, G., Willoughby, A., et al.[2020]

In a real-world study of 85 patients receiving IgPro20 for hypogammaglobulinemia, 45.9% experienced adverse events, with injection site reactions being the most common, but the treatment was generally considered safe.

The effectiveness of IgPro20 was demonstrated by a reduction in infection rates from 0.54 per patient before treatment to 0.39 during treatment, indicating it helps protect against infections in patients with primary and secondary immunodeficiencies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world results with IgPro20 for hypo- or agammaglobulinemia in Japan. Imai, K., Ishii, T., Nonoyama, S., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04640142

NCT04640142 | Study to Evaluate the Pharmacokinetics, ... Study to Evaluate the Pharmacokinetics, Efficacy, Tolerability, and Safety of Subcutaneous Human Immunoglobulin (Newnorm) in Patients With Primary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3333462/

Human normal immunoglobulin in the treatment of primary ... Replacement therapy with immunoglobulin in primary antibody deficiencies increases life expectancy and reduces the frequency and severity of infection.

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-subcutaneous-human-immunoglobulin-newnorm-for-patients-with-primary-immunodeficiency-diseases/

Study on the Effects of Subcutaneous Human ... This clinical trial investigates the efficacy of subcutaneous human immunoglobulin (Newnorm) in preventing bacterial infections in patients with Primary ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1567576915000235

20% subcutaneous immunoglobulin for patients with ... No evidence could prove that SCIG-20% was better than other immunoglobulin drugs. We do not recommend this drug for patients with PIDs based on our results.

5. tandfonline.com tandfonline.com/doi/full/10.2217/imt-2021-0313

Overview of Subcutaneous Immunoglobulin 16.5% in ... This review will focus on SCIG 16.5% products with a historical overview of development, including the early pioneers who initiated and refined IG replacement ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04640142

NCT04640142 | Study to Evaluate the Pharmacokinetics, ... Study to Evaluate the Pharmacokinetics, Efficacy, Tolerability, and Safety of Subcutaneous Human Immunoglobulin (Newnorm) in Patients With Primary ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5167020/

Efficacy, safety, tolerability and pharmacokinetics of a novel ... These results demonstrate that IGSC 20% provides an effective and well‐tolerated therapy for patients previously on intravenous or subcutaneous treatment, ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2213219825005367

Facilitated Subcutaneous Immunoglobulin 10% Safety ... This review provides an overview of data published to date relating to the safety and tolerability of fSCIG 10% for the treatment of primary ...

9. ema.europa.eu ema.europa.eu/en/documents/scientific-guideline/draft-guideline-clinical-investigation-human-normal-immunoglobulin-subcutaneous-or-intramuscular-administration-scig-imig-revision-2_en.pdf

draft-guideline-clinical-investigation-human-normal ... - EMA Replacement therapy in primary immunodeficiency ... Biological data, pharmacokinetic (PK) data and clinical evidence of efficacy and safety in ...