Proof-of-concept study for SAR445088 in chronic inflammatory demyelinating polyneuropathy (CIDP)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sanofi-Aventis Recherche & Developpement

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

13 Oct 2021 → 2 Oct 2025

Decision date (initial)

2024-06-24

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-512345-16-00

EudraCT number

2020-004006-54

WHO UTN

U1111-1246-7023

ClinicalTrials.gov

NCT04658472

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacokinetic, Others, Pharmacodynamic

Part A: Efficacy of SAR445088 across three subpopulations of CIDP patients: standard of care (SOC)-Treated, SOC-Refractory and SOC-Naive
Part B:Long-term safety and tolerability of SAR445088 in CIDP

Secondary objectives 5

1. Part A: Safety and tolerability of SAR445088 in CIDP
2. Part A: Immunogenicity of SAR445088
3. Part A: Efficacy of SAR445088 with overlapping SOC (SOC-Treated group)
4. Part B: Durability of efficacy during long-term treatment with SAR445088 in CIDP
5. Part B: Long-term immunogenicity of SAR445088 in CIDP

Conditions and MedDRA coding

Chronic inflammatory demyelinating polyradiculoneuropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adults ≥18 years of age at the time of signing the informed consent.
2. Documented definite or probable diagnosis of CIDP (typical CIDP, pure motor CIDP, or Lewis-Sumner Syndrome) according to the European Federation of Neurological Societies (EFNS)/Peripheral Nerve Society (PNS) Task Force first revision.
3. Belonging to one of the following three groups: standard-of-care (SOC)-Treated, SOC-Refractory or SOC-Naïve, as defined below. - SOC-Treated (all criteria a-c must be met): a) Documented evidence of objective response to SOC, with clinically meaningful improvement. Clinically meaningful improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT score, ≥4 points increase in RODS total score, ≥3 points increase in MRC Sum score, ≥8 kilopascal improvement in mean grip strength (one hand), or an equivalent improvement based on information documented in medical records and per the PI’s judgement. b) Must be on stable SOC therapy, defined as no change greater than 10% in frequency or dose of immunoglobulin therapy or corticosteroids within 8 weeks prior to screening, remaining at stable SOC therapy until the time of first SAR445088 dosing. c) Evidence of clinically meaningful deterioration on interruption or dose reduction of SOC therapy within 24 months prior to screening, determined by clinical examination or medical records. Clinically meaningful deterioration is defined as one of the following: ≥1-point increase in adjusted INCAT score, decrease in RODS total score ≥4 points, decrease in MRC Sum score ≥3, mean grip strength worsening of ≥8 kilopascals (one hand), or an equivalent deterioration based on information from medical records and at the PI’s judgement. - SOC-Refractory (all criteria a-d must be met): a) Evidence of failure or inadequate response to SOC defined as no clinically meaningful improvement and persistent INCAT score ≥2 after treatment for a minimum of 12 weeks on SOC prior to screening. A clinically meaningful improvement is defined as one of the following: ≥1-point decrease in adjusted INCAT score, increase in RODS total score ≥4 points, increase in MRC Sum score ≥3, mean grip strength improvement of ≥8 kilopascals (one hand), or equivalent improvement based on information from medical records and at the PI’s judgement. Or - Unable to receive or continue treatment with immunoglobulins or corticosteroids due to side effects. - b) Patient has not received immunoglobulins (IVIg or SCIg) within 12 weeks prior to screening. c) Certain immunosuppressant drugs are allowed in this group if taken for ≥6 months and at a stable dose for ≥3 months prior to screening: azathioprine, methotrexate, mycophenolate mofetil and cyclosporine. Oral corticosteroids are allowed if on a stable dose of <20 mg/day of prednisone (or equivalent dose for other oral corticosteroids) for ≥3 months prior to screening. d) INCAT score: 2-9 (a score of 2 should be exclusively from leg disability component of INCAT). - SOC-Naïve (all criteria a-c must be met): a) Participants without previous treatment for CIDP or participants who received immunoglobulins (IVIg or SCIg) or corticosteroids but were stopped for reasons other than lack of response or side effects. b) Not treated with immunoglobulins (IVIg or SCIg) or corticosteroids for at least 6 months prior to screening. c) INCAT score: 2-9 (a score of 2 should be exclusively from leg disability component of INCAT.
4. Documented vaccinations against encapsulated bacterial pathogens given within 5 years of enrollment or initiated a minimum of 14 days prior to first dose
5. A female participant must use a double contraception method including a highly effective method of birth control from inclusion and up to 52 weeks plus 30 days after the last study dose and agree not to donate eggs, ova or oocytes during this period.
6. A female participant must have a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours before the first dose of study intervention.
7. Male participants, whose partners are of childbearing potential must accept to use, during sexual intercourse, a double contraceptive method according to the following: condom plus an additional highly effective contraception
8. Male participants must have agreed not to donate sperm during the intervention and up to 52 weeks after the last dose.
9. Capable of giving signed informed consent

Exclusion criteria 19

1. Polyneuropathy of other causes, including but not limited to hereditary demyelinating neuropathies, neuropathies secondary to infection or systemic disease, diabetic neuropathy, drug- or toxin-induced neuropathies, multifocal motor neuropathy, polyneuropathy related to IgM monoclonal gammopathy, POEMS syndrome, lumbosacral radiculoplexus neuropathy, pure sensory CIDP and acquired demyelinating symmetric (DADS) neuropathy (also known as distal CIDP).
2. Any other neurological or systemic disease that can cause symptoms and signs interfering with treatment or outcome assessments.
3. Poorly controlled diabetes (HbA1c >7%).
4. Serious infections requiring hospitalization within 30 days prior to screening and any active infection requiring treatment during screening.
5. Clinical diagnosis of SLE.
6. Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator, contraindicates participation in the study. Specifically, history of any hypersensitivity reaction to SAR445088 or its components or of a severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibody.
7. Participants with a history of suicidality in the six months prior to screening or currently at risk of committing suicide.
8. Presence of conditions (medical history or laboratory assessments) that may predispose the participant to excessive bleeding or increased risk of infection.
9. Evidence of CIDP relapse within 6 weeks after receiving a vaccination.
10. Recent or planned major surgery that could confound the results of the trial or put the participant at undue risk.
11. Treatment with plasma exchange within 12 weeks prior to screening.
12. Prior treatment with rituximab or ocrelizumab in the 6 months prior to SAR445088 dosing or until return of B-cell counts to normal levels, whichever is longer.
13. Immunosuppressive/chemotherapeutic medications such as azathioprine, methotrexate, cyclophosphamide, cyclosporine, mycophenolate mofetil, tacrolimus, interferon, TNF-alpha inhibitor: within 6 months prior to dosing (except for some cases as indicated in the SOC-Refractory group).
14. Treatment (any time) with highly immunosuppressive/chemotherapeutic medications with sustained effects, eg, mitoxantrone, alemtuzumab, cladribine.
15. Treatment (any time) with total lymphoid irradiation or bone marrow transplantation.
16. Use of any specific complement system inhibitor (eg, eculizumab) within 12 weeks or 5 times the half-life of the product, whichever is longer, prior to screening.
17. Pregnant (defined as positive β-HCG blood test) or lactating females.
18. Positive result on any of the following tests: hepatitis B surface (HBsAg) antigen, anti-hepatitis B core antibodies (anti-HBc Ab)-unless anti-hepatitis B surface antibodies (anti-HBs Ab) are also positive , indicating natural immunity-, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 antibodies).
19. Evidence of IgG4 autoantibodies against paranodal proteins (NF155 and CNTN1).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Part A, SOC-Treated: Percentage of participants relapsing after withdrawal of SOC and during the SAR445088 treatment period
2. Part A, SOC-Refractory (initial and low dose group) and SOC-Naïve: Percentage of participants responding during the SAR445088 treatment period
3. Part B: Number of participants reported with adverse events

Secondary endpoints 6

1. Part A: Number of participants reported with adverse events
2. Part A: Number of participants with incidence and titer of anti-SAR445088 antibodies (ADA)
3. Part A: Percentage of participants in the SOC-Treated group improving during the overlap treatment period
4. Part B, SOC-Treated (initial dose group): Percentage of participants relapse-free during the treatment extension period
5. Part B, SOC-Refractory (initial and low dose group) and SOC-Naive: Percentage of participants with sustained response during the treatment extension period
6. Part B: Long-term immunogenicity

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sanofi-Aventis Recherche & Developpement

Sponsor organisation

Sanofi-Aventis Recherche & Developpement

Address

82 Avenue Raspail

City

Gentilly

Postcode

94250

Country

France

Scientific contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Public contact point

Organisation

Sanofi-Aventis Recherche & Developpement

Contact name

Clinical Sciences and Operations

Third parties 9

Locations

6 EU/EEA countries · 16 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 5 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