Rapid Drug Desensitization for Allergic Reactions

(PALLADIUM Trial)

Overseen By 165-402 Medical Director, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: BioMarin Pharmaceutical

Must be taking: Palynziq

Must not be taking: Beta blockers

Disqualifiers: Uncontrolled asthma, Cardiovascular disease, others

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

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

Compensation: Varies

Number of Visits: 2

10 Participants Needed

Trial Summary

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

The trial does not specify if you need to stop taking your current medications, but you cannot be on beta blockers or certain injectables with PEG, except for PEG-containing vaccines like COVID-19 vaccines.

What data supports the effectiveness of the drug Rapid Drug Desensitization for allergic reactions?

Rapid Drug Desensitization is shown to be highly effective in allowing patients with drug allergies to safely receive their necessary medications, such as antibiotics and chemotherapy, with a 99.9% success rate in delivering the full dose without severe reactions. This procedure has been successful in hundreds of cases, significantly improving patients' quality of life and treatment outcomes. ^{1 2 3 4 5}

Is rapid drug desensitization generally safe for humans?

Rapid drug desensitization is generally considered safe for humans, allowing patients with drug allergies to receive necessary medications. Most reactions during the procedure are mild, and serious reactions are infrequent. ^{1 4 5 6 7}

How is rapid drug desensitization different from other drug treatments for allergic reactions?

Rapid drug desensitization is unique because it allows patients with drug allergies to safely receive medications they are allergic to by gradually introducing small doses until the full dose is tolerated. This is particularly useful when no alternative treatments are available, enabling patients to continue using essential first-line therapies. ^{1 5 6 7 8}

What is the purpose of this trial?

The purpose of this study is to determine if rapid drug desensitization (RDD) to Palynziq will improve drug tolerability and treatment persistence in adult patients on commercial Palynziq experiencing hypersensitivity reactions (HSRs) leading to treatment interruption or reduction of dose or dosing frequency. See Section 10.8 for full list of HSR preferred terms. Study details include: * Study duration: Up to 30 weeks (up to 6 weeks for Screening, then RDD, and 24 weeks of follow-up) * RDD duration: 1 day * Palynziq dosing/follow-up duration: 24 weeks * Palynziq dosing frequency: Individualized

Research Team

Medical Director, MD

Principal Investigator

BioMarin Pharmaceutical

Eligibility Criteria

Adults with Tetrahydrobiopterin Deficiency, Phenylketonuria, or allergic reactions to Palynziq who have had to stop or reduce treatment due to hypersensitivity. Participants must be on commercial Palynziq and willing to undergo a rapid drug desensitization process.

Inclusion Criteria

Participants must be capable of giving written informed consent as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

I have phenylketonuria and am taking Palynziq under the REMS program.

I had a reaction to Palynziq that required stopping or changing the treatment.

Exclusion Criteria

Participant must not be pregnant on the day of the RDD

I do not have uncontrolled asthma, active infections, or heart disease.

I am not on any PEG injectables, except for PEG vaccines like COVID-19.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 6 weeks

Rapid Drug Desensitization (RDD)

Participants undergo a rapid drug desensitization protocol to improve drug tolerability

1 day

1 visit (in-person)

Palynziq Dosing and Follow-up

Participants receive individualized Palynziq dosing and are monitored for hypersensitivity reactions

24 weeks

1 visit (in-person), remote visits every other week from Week 2 to Week 12, then monthly until Week 24

Treatment Details

Interventions

• Rapid Drug Desensitization

Trial Overview The trial is testing whether a one-day rapid drug desensitization (RDD) procedure can help patients better tolerate Palynziq after experiencing hypersensitivity reactions. The study includes up to 30 weeks of participation with personalized dosing frequency for follow-up.

Participant Groups

Group I: RDD Experimental Treatment 1 Intervention

Participants undergoing RDD to Palynziq

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Findings from Research

Rapid drug desensitization is a safe clinical procedure that enables patients with drug hypersensitivity to continue using first-line therapies, which are generally more effective than second-line options.

This approach not only improves treatment efficacy and reduces side effects but also enhances the overall quality of life and life expectancy for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Who, What, Where, When, Why, and How of Drug Desensitization. Yang, BC., Castells, MC.[2022]

Hypersensitivity reactions (HSRs) to drugs, particularly monoclonal antibodies, have increased, impacting patients' ability to use first-line therapies and affecting their quality of life.

Rapid drug desensitization is a viable treatment for patients with HSRs, offering protection against anaphylaxis, but it should only be conducted by trained professionals due to the risks involved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century. Castells Guitart, MC.[2014]

Rapid drug desensitization (RDD) is a highly effective and safe method for administering medications to patients with drug hypersensitivity, with a success rate of 99.9% across 796 desensitizations without any fatalities.

Patients undergoing RDD experience reactions that are generally much less severe than their initial hypersensitivity reactions, making it a viable option for treating conditions requiring specific medications, such as infections and cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desensitization regimens for drug allergy: state of the art in the 21st century. Liu, A., Fanning, L., Chong, H., et al.[2022]

Rapid drug desensitization is a safe and effective method for treating patients with hypersensitivity reactions to chemotherapeutic drugs, including monoclonal antibodies, and works for both IgE and non-IgE mediated reactions.

The procedure has a low likelihood of breakthrough reactions, with most being mild, and moderate-to-severe reactions occurring infrequently, making it a reliable option for patients needing these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization. Vega, A., Jimenez-Rodriguez, TW., Barranco, R., et al.[2022]

Drug desensitization is a high-risk procedure that allows patients with hypersensitivity reactions to safely receive essential medications by gradually increasing doses until tolerance is achieved, typically over several hours to a few days.

This method is primarily used for IgE-mediated reactions, particularly with antibiotics like penicillin, and must be repeated for ongoing treatments, such as chemotherapy, due to the temporary nature of the induced tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. Cernadas, JR., Brockow, K., Romano, A., et al.[2022]

In a study involving 23 patients, 105 rapid desensitizations to monoclonal antibodies (mAbs) were successfully completed in 104 cases, demonstrating the efficacy of this method for safely re-administering medications after hypersensitivity reactions.

Although 29% of desensitizations experienced hypersensitivity reactions, these were generally milder than initial reactions, indicating that rapid desensitization can be a safe option, though the risk of reactions persists with each procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. Brennan, PJ., Rodriguez Bouza, T., Hsu, FI., et al.[2022]

Rapid desensitization protocols can effectively allow patients with drug allergies, such as to antibiotics and aspirin, to safely receive necessary medications, thus preventing severe allergic reactions like anaphylaxis.

Although these protocols have shown high success rates in clinical settings, the exact cellular and molecular mechanisms behind their effectiveness are still not fully understood, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Desensitization for drug allergy. Castells, M.[2022]

A 49-year-old patient with Castleman's syndrome successfully underwent rapid desensitization to rituximab after experiencing a hypersensitivity reaction, allowing for continued treatment.

The rapid desensitization led to significant clinical improvements, including reduced symptoms and normalization of blood parameters, suggesting it is a viable option for patients with no alternative therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab]. Boin, C., Lambert, S., Thomann, P., et al.[2017]

References

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

The Who, What, Where, When, Why, and How of Drug Desensitization. [2022]

2. Spain pubmed.ncbi.nlm.nih.gov

Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Desensitization regimens for drug allergy: state of the art in the 21st century. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization. [2022]

5. Denmark pubmed.ncbi.nlm.nih.gov

General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. [2022]

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

Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. [2022]

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

Desensitization for drug allergy. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab]. [2017]