Randomized multicenter double-blind controlled trial comparing anakinra to prednisone for gout flare in patients with chronic kidney disease stage 4-5 or kidney transplantation

2024-514347-28-00 Protocol APHP180560 Therapeutic confirmatory (Phase III) Ended

Start 2 Jun 2022 · End 12 Feb 2025 · Status Ended · 1 EU/EEA countries · 20 sites · Protocol APHP180560

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)
Status Ended
Participants planned 234
Countries 1
Sites 20

Men and women over 18 years of age with renal failure renal failure stages 3b/4/5, renal transplantation or dialysis and an untreated gout attack

To demonstrate the superiority of anakinra, the recombinant agonist of the interleukin-1 antagonist, versus prednisone in the prednisone in the treatment of gout attacks in patients with patients with chronic kidney disease stages 3b, 4 or 5, renal transplantation or dialysis.

Key facts

Sponsor
Assistance Publique Hopitaux De Paris
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Musculoskeletal Diseases [C05]
Trial duration
2 Jun 2022 → 12 Feb 2025
Decision date (initial)
2024-10-21
Transition trial
Yes
Low-intervention
No
Rare-disease indication
No
Vulnerable population
No
Funding sources
French Ministry of Health

External identifiers

EU CT number
2024-514347-28-00
EudraCT number
2019-002570-31
ClinicalTrials.gov
NCT04844814

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate the superiority of anakinra, the recombinant agonist of the interleukin-1 antagonist, versus prednisone in the prednisone in the treatment of gout attacks in patients with patients with chronic kidney disease stages 3b, 4 or 5, renal transplantation or dialysis.

Secondary objectives 12

  1. Efficacy of anakinra: To compare changes in pain from baseline to D5
  2. -Efficacy of anakinra: To compare speed of resolution of attacks(>80% improvement or pain less than 20
  3. -Efficacy of anakinra: To compare treatment response time (more than 50% improvement)
  4. -Efficacy of anakinra: To compare duration of treatment
  5. -Efficacy of anakinra: To compare number of responders (improvement at D3)
  6. -Efficacy of anakinra: To compare the number of relapses during the study month of the study
  7. -Efficacy of anakinra: To compare consumption of care during the month of the study: length of hospital stay, use of analgesics, length of time off work
  8. - Tolerance of anakinra: To compare injection-site reactions
  9. - Tolerance of anakinra: To compare decreases in neutrophils or platelets
  10. - Tolerance of anakinra: To compare decompensation of comorbidities: HTA, diabetes, dyslipidemia, obesity, CKD
  11. - Tolerance of anakinra: To compare cardiovascular events: myocardial infarction myocardial infarction, arrhythmia, heart failure relapse heart failure, stroke
  12. Tolerance of Anakinra: To compare severe infections

Conditions and MedDRA coding

Men and women over 18 years of age with renal failure renal failure stages 3b/4/5, renal transplantation or dialysis and an untreated gout attack

Study design 1 period

#TitleAllocationBlindingRoles blindedArms
1 Treatment period
During 3 to 5 days, depending on the randomisation arm, patients will receive eihter anakinra + placebo of prednisone or placebo of anakinra + predisone
 Randomised Controlled Double [{"id":87138,"code":2,"name":"Investigator"},{"id":87142,"code":3,"name":"Monitor"},{"id":87141,"code":4,"name":"Analyst"},{"id":87139,"code":1,"name":"Subject"},{"id":87140,"code":5,"name":"Carer"}] Arm anakinra + placebo of prednisone: patients will receive anakinra (100mg each two days, sc) + placebo of prednisone (1.5 tablets/day) during 3 to 5 days
Arm placebo of anakinra + predisone: patients will receive placebo of anakinra (0,67ml of 0.9%NaCL sc) + prednisone (1.5 tablets/day, 20mg tablet) during 3 to 5 days

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Adult over 18 years old
  2. - Gout attack confirmed by demonstration of urate crystals by analysis of joint fluid or tophus or by ultrasound of the affected joint and/or - Gout attack according to Nijmegen criteria (presence of a score > 8/13) according to the following items: • Man (2 pts) • Previous crisis (2 pts) • Injury of the metatarsophalangeal joint of the first ray (MTP1) (2.5 pts) • Maximum installation in less than 24 hours (0.5pt) • Redness (1 pt) • Hypertension or cardiovascular diseases (1.5 pts) • Blood uric acid > 360 µmol/l during the crisis (3.5 pts)
  3. Persistent crisis
  4. EVA > 4/10
  5. Chronic kidney disease stages 3b, 4 or 5, or kidney transplant, or dialysis
  6. Affiliation to the French social security system or CMU
  7. - Signature of informed, free and written consent for participation in the study
  8. Negative plasma pregnancy test and under effective contraception, namely hormonal contraception (Progesterone or combined Progesterone and estrogen orally, vaginally, intradermally, implant) or hormonal or mechanical IUD, in premenopausal women

Exclusion criteria 12

  1. Participation in another interventional trial including the administration of a drug
  2. Active infection
  3. Known allergy to anakinra or prednisone or their excipients
  4. Contraindication to the administration of anakinra or prednisone
  5. Neutropenia < 1000 /mm3
  6. Chronic kidney disease ≤ 3a
  7. Difficulty understanding French
  8. Illiteracy
  9. Pregnant women, parturients or breastfeeding mothers (Cf. CSP article L.1121-5)
  10. Persons deprived of liberty by a judicial or administrative decision, persons subject to psychiatric care under articles L. 3212-1 and L. 3213-1 and persons admitted to a health or social establishment to others purposes other than research (Cf. CSP article L.1121-6)
  11. Adults subject to a legal protection measure or unable to express their consent (Cf. CSP article L.1121-8)
  12. Persons not affiliated to a social security scheme or beneficiaries of such a scheme (Cf. CSP article L.1121-8-1)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. The main evaluation criterion will be the change in pain between the day of inclusion and 3 days after initiation of treatment (D3) or the day of discharge from hospitalization if this occurs before D3.

Secondary endpoints 12

  1. Efficacy of anakinra: To compare changes in pain from baseline to D5
  2. Efficacy of anakinra: To compare speed of resolution of attacks(>80% improvement or pain less than 20 mm)
  3. Efficacy of anakinra: To compare treatment response time (more than 50% improvement)
  4. Efficacy of anakinra: To compare duration of treatment
  5. Efficacy of anakinra: To compare number of responders (improvement at D3)
  6. Efficacy of anakinra: To compare the number of relapses during the study month of the study
  7. • Efficacy of anakinra: To compare consumption of care during the month of the study: length of hospital stay, use of analgesics, length of time off work
  8. Tolerance of anakinra: To compare injection-site reactions
  9. Tolerance of anakinra: To compare decreases in neutrophils or platelets
  10. Tolerance of Anakinra: To compare severe infections
  11. Tolerance of anakinra: To compare decompensation of comorbidities: HTA, diabetes, dyslipidemia, obesity, CKD
  12. •- Tolerance of anakinra: To compare cardiovascular events: myocardial infarction myocardial infarction, arrhythmia, heart failure relapse heart failure, stroke

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Kineret 100 mg/0.67 ml solution for injection in pre-filled syringe.

PRD6844804 · Product

Active substance
Anakinra
Pharmaceutical form
SOLUTION FOR INJECTION
Route of administration
SUBCUTANEOUS INJECTION
Max daily dose
100 mg milligram(s)
Max total dose
500 mg milligram(s)
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
L04AC03 — -
Marketing authorisation
EU/1/02/203/006
MA holder
SWEDISH ORPHAN BIOVITRUM AB (PUBL)
MA country
Iceland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

CORTANCYL 20 mg, comprimé sécable

PRD9995017 · Product

Active substance
Prednisone
Pharmaceutical form
TABLET
Route of administration
ORAL
Max daily dose
30 mg milligram(s)
Max total dose
150 mg milligram(s)
Max treatment duration
5 Day(s)
Authorisation status
Authorised
ATC code
H02AB07 — PREDNISONE
Marketing authorisation
34009 332 838 5 8
MA holder
CHEPLAPHARM ARZNEIMITTEL GMBH
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 2

placebo of Cortancyl 20 mg

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

NaCl 0,9% as placebo of kineret

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

251 Total trials 131 Recruiting 54 Ended
Academic / Non-commercial
Sponsor organisation
Assistance Publique Hopitaux De Paris
Address
Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City
Paris Cedex 10
Postcode
75475
Country
France

Scientific contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Coordinating Investigator

Public contact point

Organisation
Assistance Publique Hopitaux De Paris
Contact name
Coordinating Investigator

Locations

1 EU/EEA country · 20 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Ended 234 20
Rest of world — 0 —

Investigational sites

France

20 sites · Ended
Pellegrin Hospital
Rhumathology, Place Amelie Raba Leon, 33000, Bordeaux
Centre Hospitalier Sud Francilien
Rhumathology, 40 Avenue Serge Dassault, 91106, Corbeil Essonnes Cedex
Assistance Publique Hopitaux De Paris
Rhumatology, 125 Rue De Stalingrad, 93009, Bobigny Cedex
Bicetre Hospital
Nephrology, 78 Rue Du General Leclerc, 94275, Le Kremlin Bicetre Cedex
Centre Hospitalier Intercommunal Creteil
Internal medecine, 40 Avenue De Verdun, 94000, Creteil
Centre Hospitalier Universitaire Rouen
Rhumatology, 1 Rue De Germont, Bp 96031, Rouen Cedex
Groupe Hospitalier Diaconesses Croix Saint Simon
Internal medecine, 125 Rue D Avron, 75020, Paris
Assistance Publique Hopitaux De Paris
Polyclinique-SAU, 2 Rue Ambroise Pare, 75475, Paris Cedex 10
Assistance Publique Hopitaux De Paris
Rhumatology, 46 Rue Henri Huchard, 75877, Paris Cedex 18
Aura Paris
Dyalisis, 12 Rue Anselme, 93400, St Ouen Sur Seine
Centre Hospitalier Universitaire De Rennes
Rhumatology, 16 Boulevard De Bulgarie, Bp 90349, Rennes
Centre Hospitalier Regional De Marseille
Nephrology, 270 Boulevard De Sainte Marguerite, 13009, Marseille
Assistance Publique Hopitaux De Paris
Nephrology, 1 Avenue Claude Vellefaux, 75010, Paris
Groupe Hospitalier Intercommunal Le Raincy Montfermeil
Rhumatology, 10 Rue Du General Leclerc, 93370, Montfermeil
Centre Hospitalier Du Pays D Aix Centre Hospitalier Intercommunal Aix-Pertuis
Rhumatology, Avenue Des Tamaris, 13100, Aix En Provence
Groupement Des Hopitaux De L'Institut Catholique De Lille
Rhumatology, 115 Rue Du Grand But, Bp 50249 Lille, Lomme Cedex
Assistance Publique Hopitaux De Paris
Nephrology, 4 Rue De La Chine, 75020, Paris
Assistance Publique Hopitaux De Paris
Rhumatology, 2 Rue Ambroise Pare, 75475, Paris Cedex 10
Assistance Publique Hopitaux De Paris
Internal medecine, 2 Rue Ambroise Pare, 75475, Paris Cedex 10
GIE Groupe hospitalier Paris Saint-Joseph/Vinci
Rhumathologie, 185 Rue Raymond Losserand, 75014, Paris

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
France 2022-06-02 2022-06-02 2025-02-12

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_2024-514347-28-00_PROTOCOLE_ANA4CKD_public 6-0
Recruitment arrangements (for publication) Not applicable 1
Subject information and informed consent form (for publication) L1_2024-514347-28-00_NIFC_ANA4CKD 6-0
Summary of Product Characteristics (SmPC) (for publication) E1_CORTANCYL_SMPC_v1-0_20240109_ANA4CKD 1-0
Summary of Product Characteristics (SmPC) (for publication) E1_KINERET_SMPC_v1-0_20230717_ANA4CKD 1
Synopsis of the protocol (for publication) D1_2024-514347-28-00_RESUME_ANA4CKD 6-0

Application history

1 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-24 France Acceptable
2024-10-17
 2024-10-21

Related clinical trials