Rapid Drug Desensitization for Allergic Reactions
(PALLADIUM Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: BioMarin Pharmaceutical
Must be taking: Palynziq
Must not be taking: Beta blockers
Disqualifiers: Uncontrolled asthma, Cardiovascular disease, others
No Placebo Group
Prior Safety Data
Trial Summary
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
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.
12345Is 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.
14567How 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.
15678Eligibility 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
I am 18 years old or older.
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.
+2 more
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.
+6 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: RDDExperimental Treatment1 Intervention
Participants undergoing RDD to Palynziq
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Uncommon CuresChevy Chase, MD
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Who Is Running the Clinical Trial?
BioMarin PharmaceuticalLead Sponsor
References
The Who, What, Where, When, Why, and How of Drug Desensitization. [2022]Hypersensitivity reactions to drugs have increased in the past 25 years due to increased exposures and availability of efficient, targeted, and personalized medications. Rapid drug desensitization is a clinical procedure that allows for the safe administration of a drug in patients with a history of such hypersensitivity reactions. Desensitization allows the continued use of first-line therapies, leading to higher efficacy of treatment, fewer side effects, cost-effectiveness, and increased quality of life and life expectancy of patients when compared with the use of second-line therapy. In this review, we discuss the who, what, where, when, why, and how of drug desensitization.
Rapid drug desensitization for hypersensitivity reactions to chemotherapy and monoclonal antibodies in the 21st century. [2014]The frequency of hypersensitivity reactions (HSR) to drugs has risen in the last 10 years owing to increased exposure to better and more allergenic medications including monoclonal antibodies. HSRs prevent patients from using their first-line therapy, leading to decreased quality of life and life expectancy. Although premedication with antihistamines, leukotriene blockers, and corticosteroids can protect against mild-to-moderate HSR, none of these medications has provided protection against anaphylaxis. Rapid drug desensitization is a treatment option for patients with HSR to their first-line medication that protects against anaphylaxis.Although the mechanisms of drug desensitization are not completely understood, in vitro mast cell models of IgE antigen desensitization have led to the design of safe and effective in vivo protocols aimed at protecting highly sensitized patients from hypersensitivity reactions and anaphylaxis. This review provides an insight into the mechanisms of IgE/mast cell desensitization, the principles and practice of drug desensitization, and an overview of the different desensitization protocols and their safety and efficacy profiles. Drug desensitization should only be performed by allergists, trained nurses, and experienced pharmacists, since this high-risk procedure involves reintroducing allergenic medication to highly sensitized patients, with the consequent potential for severe or fatal HSRs.
Desensitization regimens for drug allergy: state of the art in the 21st century. [2022]Adverse reactions to drugs are increasingly being recognized as important contributions to disease in their own right as well as impediments to the best treatment of various conditions, including infectious, autoimmune, and neoplastic maladies. Rapid drug desensitization (RDD) is an effective mechanism for safely administering important medications while minimizing or entirely circumventing such adverse reactions in sensitized patients. We reviewed the literature on RDD in the last 10 years, including our experience from the Brigham and Women's Hospital Desensitization Program with hundreds of patients desensitized to a broad variety of drugs. RDD in our programme has been uniformly successful in patients with hypersensitivity reactions to antibiotics, chemotherapeutics, and monoclonal antibodies. Any reactions that occur during desensitization are generally much less severe than the initial hypersensitivity reaction to the drug, and patients have received the full dose of the desired medication 99.9% of the time out of (796) desensitizations. To date, there have been no fatalities. RDD is a safe and highly effective method for treating sensitized patients with the optimal pharmacologic agents. Its use should be expanded, but because patient safety is paramount, protocols must be created, reviewed, and overseen by allergist-immunologists with special training and experience in modern techniques of desensitization.
Hypersensitivity Reactions to Cancer Chemotherapy: Practical Recommendations of ARADyAL for Diagnosis and Desensitization. [2022]Rapid drug desensitization has enabled first-line therapies in patients with drug hypersensitivity reactions to chemotherapeutic drugs including monoclonal antibodies. Desensitization is a safe and highly effective procedure, not only for IgE-mediated reactions, but also for those mediated by non-IgE mechanisms. The likelihood of breakthrough reactions during desensitization is low, and most are mild; in fact, moderate-to-severe reactions are infrequent. In this document, 16 allergy departments belonging to the Spanish research network ARADyAL present a review of the available scientific evidence and provide general guidelines for the diagnosis and management of drug hypersensitivity reactions to chemotherapeutic drugs and monoclonal antibodies. Emphasis is placed on the desensitization procedure.
General considerations on rapid desensitization for drug hypersensitivity - a consensus statement. [2022]Drug hypersensitivity reactions can occur with most drugs, are unpredictable, may affect any organ or system, and range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. However, for certain patients, the particular drug may be essential for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance of a compound responsible for a hypersensitivity reaction. It is performed by administering increasing doses of the medication concerned over a short period of time (from several hours to a few days) until the total cumulative therapeutic dose is achieved and tolerated. It is a high-risk procedure used only in patients in whom alternatives are less effective or not available after a positive risk/benefit analysis. Desensitization protocols have been developed and are used in patients with allergic reactions to antibiotics (mainly penicillin), insulins, sulfonamides, chemotherapeutic and biologic agents, and many other drugs. Desensitization is mainly performed in IgE-mediated reactions, but also in reactions where drug-specific IgE have not been demonstrated. Desensitization induces a temporary tolerant state, which can only be maintained by continuous administration of the medication. Thus, for treatments like chemotherapy, which have an average interval of 4 weeks between cycles, the procedure must be repeated for every new course. In this paper, some background information on rapid desensitization procedures is provided. We define the drugs and drug reactions indicated for such procedures, describe the possible mechanism of action, and discuss the indications and contraindications. The data should serve as background information for a database (accessible via the EAACI-homepage) with standardized protocols for rapid desensitization for antibiotics, chemotherapeutic agents, monoclonal antibodies/fusion proteins, and other drugs.
Hypersensitivity reactions to mAbs: 105 desensitizations in 23 patients, from evaluation to treatment. [2022]Rapid desensitization, a procedure for graded drug administration, allows for the safe readministration of a medication after certain types of hypersensitivity reactions (HSRs) and is indicated in cases in which there are no reasonable therapeutic alternatives. The use of rapid desensitization for HSRs to mAbs has not been validated.
Desensitization for drug allergy. [2022]Desensitization for drug allergy is the induction of temporary clinical unresponsiveness to drug antigens. Gradual reintroduction of small doses of drug antigen at fixed time intervals allows for the delivery of full therapeutic doses, protecting patients from anaphylaxis. Rapid desensitizations permit the use of essential antibiotics in severely infected allergic patients or aspirin in aspirin-sensitive cardiac patients undergoing revascularization. We review the indications and outcomes of recent protocols for desensitization to antibiotics and aspirin.
[Castleman's disease: Rapid desensitization for hypersensitivity reaction to rituximab]. [2017]Rapid desensitization allows secure administration of a drug and is indicated when there is no therapeutic alternative.