REduCing Immunogenicity to PegloticasE (RECIPE) Study

NCT03303989 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 300000591
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Pegloticase treatment for chronic refractory gout is limited by immunogenicity. The investigators propose the REduCing Immunogenicity to PegloticasE (RECIPE) trial to begin to investigate the question of whether a short course of immune modulating therapy with mycophenolate mofetil can significantly and safely attenuate immunogenicity to pegloticase and ensure patients afflicted with chronic refractory gout have better treatment outcomes and improved quality of life.

Conditions

Gout Chronic

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants Achieving and Maintaining an sUA ≤ to 6 Milligram Per Deciliter (mg/dL) Through 12 Weeks

  Proportion of participants achieving and maintaining an sUA ≤ to 6 mg/dL through 12 weeks, compared to concurrent controls.

  12 weeks

Study Arms (2)

pegloticase + MMF

EXPERIMENTAL

Participants randomized to this arm will receive pegloticase + mycophenolate mofetil.

Drug: Pegloticase 8 MG/ML [Krystexxa]; Drug: MMF

pegloticase + placebo

PLACEBO COMPARATOR

Participants randomized to this arm will receive pegloticase + placebo

Drug: Placebo; Drug: Pegloticase 8 MG/ML [Krystexxa]

Interventions

Pegloticase 8 MG/ML [Krystexxa] DRUG

Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.

Also known as: Krystexxa

pegloticase + MMF

MMF DRUG

Participants randomized to the pegloticase + MMF arm will start two week run-in on 1) mycophenolate mofetil at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period, Mycophenolate mofetil therapy will continue for 12 weeks at the highest tolerated dose. After the 12-week combination mycophenolate mofetil and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.

Also known as: Cell Cept

pegloticase + MMF

Placebo DRUG

Participants randomized to the pegloticase + placebo arm will start two week run-in on 1) placebo at 500 mg/BID or the first week, titrating dose up to 1000mg/BID for the second week of run-in prior to the first infusion; and 2) Pegloticase 8 mg IV every two weeks following 2 week run-in period. After the 12-week combination placebo and pegloticase study period, participants will continue open label pegloticase therapy for an additional three months.

pegloticase + placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women \> 18 years of age
• Diagnosed with chronic refractory gout\*
• Defined as: Persons whose signs and symptoms are inadequately controlled with urate lowering therapy (e.g. xanthine oxidase inhibitors or uricosuric agents) at a medically appropriate dose or for whom these drugs are contraindicated.

You may not qualify if:

• Any serious acute bacterial infection (2 weeks prior to Visit 1), unless treated and completely resolved with antibiotics
• Severe chronic or recurrent bacterial infections (such as recurrent pneumonia, chronic bronchiectasis)
• Current immunocompromised condition, including current or chronic treatment with immunosuppressive agents
• Subjects at risk for tuberculosis. Specifically, subjects with: i) current clinical, radiographic or laboratory evidence of active or latent TB; ii) a history of active TB within the last 3 years even if it was treated; iii) a history of active TB greater than 3 years ago unless there is documentation that the prior anti-TB treatment was appropriate in duration and type
• Known Hepatitis B surface antigen-positive or Hepatitis B DNA positive subjects
• Known Hepatitis C RNA-positive subjects
• Human Immunodeficiency Virus (HIV) infection
• G6PD deficiency (tested at Screening Visit 1)
• Severe chronic renal impairment (glomerular filtration rate \[GFR\] \<25 mL/min/1.73 m2) or currently on dialysis
• Subjects having any transplant surgery requiring maintenance immunosuppressive therapy
• Non-compensated congestive heart failure, uncontrolled arrhythmia, treatment for acute coronary syndrome (myocardial infarction or unstable angina), or hospitalization for congestive heart failure within 3 months of screening or uncontrolled blood pressure (\>160/100 mm Hg) at baseline (Screening Visit 1 and Week 0/Baseline visits)
• Participants who are pregnant, planning to become pregnant, breastfeeding, or not on an effective form of birth control (defined in Study Protocol section 7.1)
• Prior treatment with pegloticase, another recombinant uricase, or concomitant therapy with a polyethylene glycol (PEG)-conjugated drug
• Known allergy to pegylated products or history of anaphylactic reaction to a recombinant protein or porcine product
• Subjects in whom MMF treatment is contraindicated or considered inappropriate

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• University of Michigan: collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

• Khanna PP, Khanna D, Cutter G, Foster J, Melnick J, Jaafar S, Biggers S, Rahman AKMF, Kuo HC, Feese M, Kivitz A, King C, Shergy W, Kent J, Peloso PM, Danila MI, Saag KG. Reducing Immunogenicity of Pegloticase With Concomitant Use of Mycophenolate Mofetil in Patients With Refractory Gout: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2021 Aug;73(8):1523-1532. doi: 10.1002/art.41731. Epub 2021 May 19.

  PMID: 33750034 DERIVED

MeSH Terms

Interventions

Pegloticase

Results Point of Contact

• Title: Jeff Foster
• Organization: UNIVERSITY OF ALABAMA AT BIRMINGHAM

pjfoster@uabmc.edu

2059966086

Study Officials

• Kenneth G Saag, MD

  Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: OTHER

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Phase II, double blind, placebo controlled multisite proof-of-concept trial in subjects initiating pegloticase for treatment of chronic gout

Study Record Dates

• First Submitted: September 29, 2017
• First Posted: October 6, 2017
• Study Start: June 14, 2018
• Primary Completion: April 27, 2020
• Study Completion: March 31, 2021
• Last Updated: March 16, 2022
• Results First Posted: November 10, 2021

Record last verified: 2022-03

Locations

US (1)