Rituximab-induced remission in CIDP (ReCIX study)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Immune system processes [G12], Diseases [C] - Nervous System Diseases [C10]

Trial duration

7 Oct 2024 → ongoing

Decision date (initial)

2024-08-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Amsterdam UMC

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacoeconomic, Therapy, Efficacy, Safety

The main goal of this study is to assess whether adding RTX to a limited period of IVIg treatment leads to long-term remission and discontinuation of IVIg, reducing the inconvenience of regular Ig infusions and related health care costs

Secondary objectives 1

1. Explore the feasibility of introducing rituximab as alternative maintenance treatment in patients with CIDP in patients who experience a relapse after at least 6 months after last RTX treatment (long term follow-up)

Conditions and MedDRA coding

Chronic inflammatory demyelinating polyneuropathy (CIDP)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

1. Inclusion criteria Group 1 (new patients): - CIDP according to the EAN/PNS criteria (According to the guideline, symptoms should be developing for at least eight week, mainly to distinguish CIDP from acute polyneuropathy (Guillain Barre syndrome, GBS). However, in some cases, symptoms progress rapidly and lead to severe disability, rendering early treatment necessary. To this end, patients with progressive symptoms for at least four weeks who are strongly suspected of having CIDP may also be included in this trial, provided there are no signs of a different disease (such as GBS or vasculitis neuropathy) - Untreated - Men and women aged between 18 and 80 years - Sufficient CIDP-related disability, as judged by treating physician to warrant IVIg and RTX treatment - Capable of giving signed informed consent
2. Inclusion criteria Group 2 (patients on maintenance treatment IVIg or SCIg): - CIDP according to the EAN/PNS criteria on maintenance treatment (stable dose/interval of at least 4 infusions or 3 months), including one of the following categories: a) patients with wear-off symptoms before next IVIg infusion captured by at least the minimal clinical important difference (MCID) on at least one outcome measure b) patients with a failed withdrawal attempt in the last 12 months captured by at least an MCID on at least one outcome measure c) patients with an increase of IVIg/SCIg dose/interval in the last 12 months leading to improvement by at least the MCID on at least one outcome measure, see below. We will use the most commonly used MCID criteria, namely: 1) one point on the INCAT disability score (1-10); 2) 4 points on a centile score on I-RODS (disability, 1-100); 3) 2 points on the MRC sum score (muscle strength, 0-60) and 4) 8 kPa on Vigorimeter (grip strength, single or both arms, variable range). - Men and women aged between 18 and 80 years - Capable of giving signed informed consent.

Exclusion criteria 16

1. Use of drugs associated with a demyelinating neuropathy in the last six months
2. Serious co-morbidity as judged by treating physician.
3. Pregnancy or nursing mother; intention to become pregnant during the course of the study; female patients of childbearing potential either not using or not willing to use a medically reliable method of contraception for the entire duration of the study.
4. No written informed consent
5. Known serious adverse events with previous IVIg or RTX treatment. Hypersensitivity to RTX or any component of the formulation. Hypersensitivity to the human immunoglobulins or to any of the excipients. Known selective IgA deficiency patients who developed antibodies to IgA.
6. Paranodopathy with demonstrated (paranodal) antibodies, previously considered part of CIDP spectrum (in these cases rituximab is preferred treatment)
7. Positive hepatitis B and C serology suggesting active/untreated infection (HBsAg, anti-HB core en anti-HBs and HCV antistof (IgG))
8. Ongoing immunosuppressive treatment for other indications.
9. Immunosuppressive treatment other than (already discontinued) corticosteroids in last 6 months.
10. IVIg interval of once every 6 weeks or more than 6 weeks (applies to Group 2 only)
11. Obesity (BMI > 35)
12. Known active malignancy, (not in remission), currently treated with chemotherapy or immunomodulatory drugs, or with a life expectancy of less than 1 year.
13. History of recurrent/chronic infections
14. Active, severe infections (such as tuberculosis, sepsis and opportunistic infections)
15. Patients in a severely immunocompromised state
16. Severe heart failure (New York Heart Association Class IV) or severe, uncontrolled cardiac disease.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Remission at 52 weeks after start of RTX, i.e., no need of additional treatment after RTX treatment.

Secondary endpoints 1

1. Stability on treatment at 104 weeks of follow-up.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC Stichting

Sponsor organisation

Amsterdam UMC Stichting

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC Stichting

Contact name

Filip Eftimov

Public contact point

Organisation

Amsterdam UMC Stichting

Contact name

Filip Eftimov

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 9 files

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

Application history

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