Isatuximab in type I cryoglobulinemia: A prospective pilot study ICE STUDY

Overview

Sponsor-declared trial summary

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] - Immune System Diseases [C20]

Trial duration

10 Feb 2022 → 28 Jan 2025

Decision date (initial)

2024-11-29

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Sanofi

External identifiers

EU CT number

2024-515039-31-00

EudraCT number

2021-001992-17

ClinicalTrials.gov

NCT05114109

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to assess the complete clinical response rate of Isatuximab in type I IgG cryoglobulinemia.

Secondary objectives 14

1. Safety and tolerability of treatment as assessed by frequency and severity of adverse clinical events
2. Early complete response rate at W12
3. Complete, partial (improvement in some but not all organs involved at baseline) and non clinical (no clinical improvement) response rate at W12 and W20
4. Rate of cryoglobulinemia clearance
5. Rate of negativation of rheumatoid factor activity
6. Rate of normalization of C4 complement level
7. Early failure rate at W4 (non clinical response at W4)
8. Clinical relapse rate and the time to relapse
9. Course of plasma cell associated disorder
10. Evolution of gammaglobulin level
11. Quality of life scores (SF-36)
12. Rate of infections (severe or not) and other complications
13. Birmingham Vasculitis Activity Score (BVAS)
14. Immunomonitoring (deep immunophenotyping, cytokines production, spectrometry, Fish analysis, single plasma cell repertoire)

Conditions and MedDRA coding

Isatuximab in type I cryoglobulinaemia: A prospective pilot study

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age > 18 years
2. Written informed consent
3. Monoclonal gammopathy of unknown significance (MGUS) with monoclonal IgG component
4. Active cryoglobulinemia vasculitis defined by positive (or history of positive) type I IgG cryoglobulinemia and a clinically active cryoglobulinemia with skin, joint, renal, pulmonary, cardiovascular, muscular, digestive, central and/or peripheral neurological involvement,
5. Treated naïve or relapsers type I cryoglobulinemia patients
6. Affiliated to National French social security system
7. Contraception : a) Male participants: A male participant must agree to use a highly effective method of contraception during the participation period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period. b) Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and with at least one of the following conditions:  Not a female of childbearing potential (FCBP), OR  A FCBP who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 24 hours of starting study medication and must apply a highly effective method of contraception during the participation period and for at least 5 months after the last dose of study treatment and refrain from donating oocyte during this period
8. HIV negative serology; negative HBs Ag test; HCV negative serology or negative HCV RNA if positive HCV serology within 3 months prior inclusion

Exclusion criteria 16

1. Patient with a vasculitis unrelated to cryoglobulinemia
2. Patient with non-active cryoglobulinemia vasculitis,
3. Patient with diagnosis of multiple myeloma, except indolent myeloma
4. Patient treated with immunosuppressant (e.g alkylating agent, Rituximab, chemotherapy for plasma-cell neoplasms) introduced or increased in the month prior to the inclusion,
5. Live vaccines within 30 days prior to baseline or concurrently with Isatuximab
6. Infection requiring hospitalization and/or use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days prior Day 0.
7. Active tuberculosis
8. HIV positive, positive Ag HbS, positive HCV RNA
9. Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results.
10. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents.
11. Hypersensitivity to the active substances (isatuximab and premedication) or to any of their excipients
12. Received any investigational drug within 14 days prior to inclusion or within 5 half-lives of the investigational drug, whichever is longer.
13. Participation in another interventional study or being in the exclusion period at the end of a previous study.
14. Vulnerable populations o pregnant or breastfeeding women o Persons deprived of liberty by judicial or administrative decision o Persons under psychiatric care without their consent o Adults subject to a legal protection measure o Persons unable to express their consent
15. Neutrophiles < 1000/mm3
16. Plaquettes < 75000/mm3

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Complete clinical response rate of cryoglobulinemia vasculitis symptoms at week (W) 20

Secondary endpoints 13

1. Safety and tolerability of treatment as assessed by frequency and severity of adverse clinical events at W20
2. Complete, partial and non-clinical response rate at W12, and at W20.
3. Rate of cryoglobulinemia clearance, of negativation of rheumatoid factor activity and of normalization of C4 complement level at W12, and at W20.
4. Rate of early failures (non-clinical response at W4),
5. Rate of renal complete remission defined as proteinuria <0.5g/24h or proteinuria/creatininuria <50 mg/mmol, disappearance of hematuria, and glomerular filtration rate ≥ 60ml/min/1.73m² at W12, and at W20.
6. Clinical relapse rate defined by de novo appearance or reappearance of a manifestation attributable to cryoglobulinemia vasculitis during 48 weeks of follow-up,
7. Rate and time to relapse from baseline to W48
8. Course of plasma cell associated disorder W12, and at W20.
9. Mean change of gammaglobulin level from baseline to W20
10. Quality of life assessed by the mean variation of the SF-36 over the 20 weeks,
11. Rate of infections (severe or not) and other complications during the 48 weeks of follow-up
12. Proportion of patients remaining in remission with a BVAS=0 at baseline, W12, and W20.
13. Evolution of Immunomonitoring (deep immunophenotyping, cytokines production, spectrometry, Fish analysis, single plasma cell repertoire) at baseline, week 12, and week 20

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

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

SAADOUN

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

SAADOUN

Locations

1 EU/EEA country · 17 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 4 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