A double-blind, placebo-controlled, randomized withdrawal study of canakinumab in pyogenic sterile arthritis pyoderma gangrenosum and acne (PAPA) syndrome

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IRCCS Istituto Giannina Gaslini

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

2 Feb 2024 → ongoing

Decision date (initial)

2024-11-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Academic study; IMP donated by Novartis (Canakinumab) with a funding of 30.000 €

External identifiers

EU CT number

2024-517155-13-00

EudraCT number

2021-005754-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Provide the first evidence of the actual efficacy of IL-1 blockade in a potentially devastating inflammatory condition, using canakinumab

Conditions and MedDRA coding

PAPA syndrome

Regulatory references

Plan to share IPD

Yes

IPD plan description

Plan to produce publications on relevant national and international rheumatologic medical journals

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Clinical diagnosis of PAPA with active flare at the time of enrolment.
2. Mutation of the PSTPIP1 gene.
3. Patient’s written informed consent from those ≥ 18 years of age must be obtained before any assessment is performed. Parent or legal guardian’s written informed consent and child’s assent, if appropriate, are required before any assessment is performed for patients < 18 years of age.
4. Male and female patients.

Exclusion criteria 13

1. Use of the following therapies: a. Glucocorticoids (prednisone equivalent > 0.2 mg/kg/day [or greater than the maximum of 10 mg/ day for children over 60 kg]) within 1 week prior to Baseline b. Anakinra within 72 hours prior to Baseline c. Other biologics (including canakinumab) or immunosuppressants 2 half-life prior to Baseline.
2. Any conditions or significant medical problems which in the opinion of the investigator immunocompromises the patient and/ or places the patient at unacceptable risk for immunomodulatory therapy such as: a. Absolute neutrophil count <1.0 x 109/L or below b. Thrombocytopenia Platelets <10.0 x 109/L c. Any active or recurrent bacterial, fungal (with exception of onychomycosis) or viral infection. At least 1 month should elapse between the complete resolution of a severe infection, requiring hospitalization or systemic antibiotic therapy before the inclusion in the study d. Presence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B (HBsAg) or Hepatitis C (HCV) infections based on screening lab results specific hepatitis serology that leads to exclusion. e. Clinical evidence or history of multiple sclerosis or other demyelinating diseases, or Felty’s syndrome
3. History or evidence of tuberculosis (TB) (active or latent) infection or one of the risk factors TB such as but not limited or exclusive to: a. History of any of the following: residence in a congregate setting (e.g. jail or prison, homeless shelter, or chronic care facility), substance abuse (e.g. injection or non-injection); health-care workers with unprotected exposure to patients who are at high risk of TB or patients with TB disease before the identification and correct airborne precautions of the patient, or b. Close contact (i.e. share the same air space in a household or other enclosed environment for a prolonged period (days or weeks, not minutes or hours) with a person with active pulmonary TB disease within the last year, or c. Evidence of TB infection (active or latent) determined by positive QuantiFERON (QFT-TB G In-Tube) test or positive Purified Protein Derivative (PPD) test (≥5 mm induration) at screening or within 2 months prior to the screening visit, according to the national guidelines. If presence of TB infection (active or latent) is established then treatment for TB as per national guidelines must have been initiated or completed prior to randomization. In the absence of national guidelines, the following has been demonstrated: TB has been treated adequately by antibiotics, cure can be demonstrated and risk factors resulting in TB exposure and contracting have been removed.
4. Elevated alanine aminotransferase (ALT) ≥3x ULN (if ALT at screening is >3x but <5x ULN, a re-test will be allowed. If ALT at re-test is <3x ULN and confirmed at another re-test, the patient will be eligible for participation).
5. Elevated aspartate aminotransferase (AST) ≥3x ULN (if AST at screening is >3x but <5x ULN, a re-test will be allowed. If AST at re-test is <3x ULN and confirmed at another re-test, the patient will be eligible for participation)
6. Increase in total bilirubin (TBL) defined as per CTC Grade ≥2: TBL >1.5x ULN
7. Administration of any investigational drug or implantation of investigational device, or participation in another trial, within 30 days before screening.
8. Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose
9. Donation or loss of blood (amount depending on age and weight, 10-20% or more of volume, within 8 weeks prior to first dosing, or longer if required by local regulation). Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
10. Female adolescents (≤18 years of age) of childbearing potential who do not agree to abstinence or, if sexually active, do not agree to the use of contraception as defined in the exclusion criterion for women of child bearing potential.
11. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment.
12. Known allergy or hypersensitivity to any component the IMP
13. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To determine whether canakinumab administered every 4 weeks is able to prevent disease flares when compared to placebo in canakinumab-responder patients.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IRCCS Istituto Giannina Gaslini

Sponsor organisation

IRCCS Istituto Giannina Gaslini

Address

Via Gerolamo Gaslini 5

City

Genoa

Postcode

16147

Country

Italy

Scientific contact point

Organisation

IRCCS Istituto Giannina Gaslini

Contact name

Marco Gattorno

Public contact point

Organisation

IRCCS Istituto Giannina Gaslini

Contact name

Marco Gattorno

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

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

Results and documents

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

Documents 8 files

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

Application history

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