“A Phase II, double-blinded, placebo-controlled clinical trial to evaluate the safety and efficacy of mesenchymal cells (MSV-ALLO®) in the treatment of lupus nephritis”

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Universitario Rio Hortega

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

13 Sep 2022 → ongoing

Decision date (initial)

2024-11-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514750-67-00

EudraCT number

2022-000243-80

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

General: The main objective of this trial is to evaluate the safety and efficacy of MSV-allo® compared to placebo in obtaining complete or partial remission in active LN. Principal: Proportion of patients achieving complete or partial response at week 24, relative to baseline, in the treatment group compared to the placebo group .

Secondary objectives 9

1. Time to achieve complete or partial remission after transplantation with MSV-allo®.
2. Time to maintain response.
3. Effect on corticosteroids use reduction during induction period.
4. Effect on immunosuppressants use reduction during induction period.
5. Safety, tolerability and immunogenicity profiles of MSV-allo® in Lupus nephritis patients.
6. MSV-allo® effect on pacients life quality
7. Effect of MSV-allo® in reducing the damage accumulated by SLE
8. Effect on proteinuria
9. Effect on the SLEDAI-2K index

Conditions and MedDRA coding

Lupus Nephritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Females or males aged ≥ 18 years who give written informed consent at the screening visit.
2. Systemic Lupus Erythematosus Diagnosis by meeting at least 4 criteria of the 11 included in ACR classification and/or SLICC criteria, at screening visit.
3. Lupus Nephritis Diagnosis according to 2003 International Society of Nephrology and Renal Pathology Society classification, by biopsy performed no more than 6 months prior to the screening visit if including from the induction period and performed no more than 1 year if including with moderate/severe recurrence.
4. No response, or partial response, to standard treatment, or moderate/severe recurrence of lupus nephritis
5. SLEDAI-2K # 10 during the screening period
6. Women of childbearing age must use effective methods of contraception to prevent pregnancy
7. Have been vaccinated against pneumococcus and influenza at vaccination campaign time

Exclusion criteria 25

1. *Previous treatments related: 1.-Use of corticosteroids or mycophenolate above allowed doses for induction, according to Systemic Autoimmune Diseases Group of Internal Medicine Spanish Society and Nephrology Spanish Society Consensus Document.
2. 3. Active cardiac arrhythmia or significant ECG clinical abnormalities at screening visit or on randomization day which, according to investigator, sponsor, or designee opinion, constitute an inappropriate risk or contraindication to study participation.
3. 4. Thromboembolic episodes 12 months prior to or at screening visit, whether or not related to associated antiphospholipid syndrome, or inadequate anticoagulation testing 6 weeks immediately prior to or during the screening visit.
4. 5. Central nervous system SLE active considered severe or progressive (recent or uncontrolled seizures, anticonvulsant therapy changes in the 3 months prior to the screening visit, or leading to significant cognitive impairment).
5. 6. Diagnosis of any demyelinating disease such as multiple sclerosis or optic neuritis.
6. 7.Comorbidities that require treatment with systemic corticosteroids (oral, rectal or injectable) such as asthma or inflammatory bowel disease
7. 8. Previous or plans for organ transplantation
8. 9. Active viral, bacterial or fungal infection clinically significant, or any major episode of infection which required hospitalization or parenteral treatment in 4 weeks prior to the screening visit, during the screening visit, or anti-infective treatment completion in the 2 weeks prior to or during the screening visit, or recurrent infections (three or more same type of infection cases in a period of 12 consecutive months). Vaginal candidiasis, onychomycosis and controlled genital or oral herpes simplex virus would not be reasons for exclusion.
9. 10. History or positive result for human immunodeficiency virus (HIV) test, hepatitis C antibodies and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg+), and/or total IgM antibodies to hepatitis B nuclear antigen at screening
10. 11. Diagnosis of active or latent tuberculosis by a purified protein derivative TB skin test (induration # 5 mm) or a positive Quantiferon test result, at screening or 3 months prior to the screening visit. Patients who have completed adequate prior treatment or who are receiving treatment will not repeat the test. Patients who are receiving adequate TB treatment for at least 4 continuous weeks prior to the screening visit and who are expected to complete the treatment regimen will not be excluded
11. 12. Presence of class 3 or 4 uncontrolled congestive heart failure according to the New York Heart Association
12. 2.- Use of rituximab, belimumab, ocrelizumab or other biological therapies against B cells 6 months prior to screening
13. 13. Active cancer
14. 14. Major surgical intervention within 6 weeks prior to the screening visit or planned during the trial period, including follow-up.
15. 15. Pregnant or lactating women
16. 3.-Use of cyclophosphamide at any time during 6 months prior to selection.
17. 4.- Use of any tumor necrosis factor inhibitor therapy at any time during 6 months prior to selection
18. 5.- Central nervous system SLE active considered severe or progressive (recent or uncontrolled seizures, anticonvulsant therapy changes in the 3 months prior to the screening visit, or leading to significant cognitive impairment)
19. 6.- Diagnosis of any demyelinating disease such as multiple sclerosis or optic neuritis
20. 7.- Comorbidities that require treatment with systemic corticosteroids (oral, rectal or injectable) such as asthma or inflammatory bowel disease
21. *Medical conditions related 1.- Any medical condition, including an uncontrolled disease other than SLE, that, in investigator opinion, sponsor or designee, represents an inappropriate risk or trials participation contraindication or would interfere with trial objectives , conduct or evaluation.
22. 2. Cardiac, peripheral or cerebrovascular cardiovascular episodes during 6 months prior to screening visit.
23. *Laboratory abnormalities 1. Clinically significant abnormalities in laboratory tests not attributed to active SLE
24. 2. Chest X-ray significant abnormalities indicating active TB. The chest x-ray must have been done within 3 months prior to the screening visit or during the screening period.
25. *Other 1. Legal incapacity

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the proportion of patients who have achieved complete response or partial response at week 24, relative to their baseline (treatment visit), in the treatment group compared to the placebo group.

Secondary endpoints 8

1. Proportion of patients at week 24 whose dose of prednisone-equivalent corticosteroids has been reduced relative to the screening visit by # 25% and to a dose # 7.5 mg/day and who have no exacerbation BILAG A or 2B . A BILAG A or 2B exacerbation is defined as at least one new BILAG A organic domain score or at least 2 new BILAG B organic domain scores compared to the screening visit.
2. Proportion of patients at each visit whose prednisone-equivalent dose has been reduced relative to the screening visit by # 25% and at a dose # 7.5 mg/day, and who do not have any BILAG A or 2B exacerbations at the disease activity
3. Proportion of patients at week 24 with a reduction relative to the screening visit in the daily dose of prednisone-equivalent corticosteroids of 0-<25%, 25%-50%, >50%.
4. Cumulative dose of prednisone-equivalent corticosteroids from the screening visit to week 24
5. Proportion of patients who before week 24 have reduced the dose of immunosuppressants and who do not present any BILAG A or 2B exacerbation
6. Change from day 1 (treatment) in SF-36 and LupusQoL scores
7. Change from day 1 (treatment) in proteinuria levels
8. Change from day 1 (treatment) in the SLEDAI-2K index.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Universitario Rio Hortega

Sponsor organisation

Hospital Universitario Rio Hortega

Address

Calle Dulzaina 2

City

Valladolid

Postcode

47012

Country

Spain

Scientific contact point

Organisation

Hospital Universitario Rio Hortega

Contact name

Julia Barbado Ajo

Public contact point

Organisation

Hospital Universitario Rio Hortega

Contact name

Julia Barbado Ajo

Locations

1 EU/EEA country · 1 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

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