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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether rapid drug desensitization can help individuals with phenylketonuria (PKU) better tolerate Palynziq, a drug they are already taking. Some people with PKU experience allergic reactions to Palynziq, leading them to stop or reduce their dosage. The study aims to determine if desensitization can enable them to continue their treatment. It includes a one-day desensitization process followed by 24 weeks of follow-up. Individuals who have experienced allergic reactions to Palynziq and had to interrupt or adjust their dosing are well-suited for this trial. As a Phase 4 trial, it involves an FDA-approved treatment and seeks to understand how it can benefit more patients.

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 is the safety track record for Rapid Drug Desensitization?

Studies have shown that rapid drug desensitization (RDD) is generally safe and effective for individuals with allergic reactions to medications. For example, one study examined 413 cases and found that a standardized 12-step RDD process was safe and had become a common practice for managing drug allergies. Another study confirmed that RDD is a safe option for those with immediate allergic reactions to drugs, though some individuals might still experience mild reactions. Overall, RDD is considered a reliable method to help individuals continue taking their prescribed medications without severe allergic reactions. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about Rapid Drug Desensitization (RDD) for allergic reactions because it offers a unique and faster way to allow patients to tolerate medications they are allergic to, such as Palynziq. Unlike traditional desensitization methods, which can be time-consuming and may not always be effective, RDD is designed to quickly build up the patient's tolerance to the drug by administering gradually increasing doses over a short period. This approach could significantly reduce the risk of severe allergic reactions and improve patient outcomes by allowing them to safely receive the benefits of essential medications without prolonged delays.

What evidence suggests that rapid drug desensitization is effective for allergic reactions?

Research has shown that rapid drug desensitization (RDD) is highly effective, with success rates ranging from 78.9% to 100%. This allows most patients to continue treatment despite allergic reactions. In this trial, participants will undergo RDD specifically for Palynziq. RDD proves especially beneficial for individuals who must continue important medications like Palynziq despite allergies. Studies indicate that RDD is safe and cost-effective, enabling patients to maintain necessary medications without major issues. In clinical experiences, some patients experienced reactions during the RDD process, but these were typically manageable. Overall, RDD offers a promising approach to managing drug allergies while maintaining essential treatments. ^{2 4 5 6 7}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

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

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

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 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.

Participants may not be currently participating in an interventional study of any investigational product, device, or procedure, or any other BioMarin clinical trial or post-marketing study

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40011988

Rapid drug desensitization in seven patients with delayed ... Objective: This case series aims to explore the rationale and outcomes of RDD in managing delayed DHRs associated with targeted therapies.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1081120625002352

Rapid desensitization in patients with immediate ... We evaluated the efficacy, safety, and outcomes of RDD—including the shorter 2-bag protocol for patients with mild reactions—and identified risk factors for ...

3. journals.lww.com journals.lww.com/apallergy/fulltext/9900/a_systematic_review_of_the_outcomes_of.149.aspx

A systematic review of the outcomes of desensitization for... Desensitization success rates ranged from 78.9% to 100% with a range of protocols employed across studies. Investigations such as patch tests ...

4. jaci-inpractice.org jaci-inpractice.org/article/S2213-2198(16)00011-8/fulltext

Safety, Costs, and Efficacy of Rapid Drug Desensitizations ... Conclusions. RDD is cost effective and safe for allergic patients with cancer and chronic disease to remain on first line therapy.

5. frontiersin.org frontiersin.org/journals/allergy/articles/10.3389/falgy.2024.1460326/full

Single center experience with more than 600 drug ... Regarding clinical outcomes, it was observed that 50 patients (20.7%) experienced HSRs during the desensitization protocol. Of these, 31 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8974726/

Use of Rapid Drug Desensitization in Delayed ... Rapid drug desensitization (RDD) has shown to be a safe and effective procedure for patients presenting with an immediate drug hypersensitivity reaction (DHR) ( ...

7. brighamandwomens.org brighamandwomens.org/assets/BWH/medicine/rheumatology-immunology-allergy/pdfs/desensitizations-413-jaci-castells-2008.pdf

Outcomes and safety of rapid desensitization in 413 cases Conclusions: Our standardized 12-step protocol for rapid drug desensitization is safe and effective and has been adopted as the standard of care ...