Cladribine vs Placebo for Non-active Progressive Multiple Sclerosis (CLASP-MS).

NCT05961644 | Recruiting Phase 2 DMC

• 4 other identifiers: 504-15-021-210032022-000036-322021/ABM/02/00002/P/02DBL.474.362.2022
• Study Type: interventional
• Target: 188
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate the efficacy and safety of subcutaneously administered cladribine versus placebo to stop inflammation and treat disease progression of non-active secondary progressive multiple sclerosis. Multiple sclerosis is an inflammatory disease of the central nervous system. In most patients, it starts with a relapsing course (RMS) which is caused by acute inflammatory lesions in the brain and spinal cord. RMS transforms at later stages into progressive disease (secondary progressive MS). Currently approved disease-modifying treatments are effective in reducing clinical relapses and brain and spinal lesions visible in MR, but they perform poorly in preventing disease progression and overall disability accumulation. The growing evidence shows that disease progression partially depends on chronic inflammation present in the CNS. Drugs, which may cross the blood-brain barrier and reach inflammatory cells residing in the CNS might be effective in this stage of the disease. Cladribine is one of the DMT approved for RMS. It is a synthetic purine analog with selective lymphocyte toxicity, which enter the CNS and is found in cerebrospinal fluid. In patients treated with cladribine, the oligoclonal bands tend to disappear proving that neuroinflammation is diminished. The participants of this clinical trial with the later non-active stage of MS are enrolled to be treated with cladribine subcutaneously or a non-active comparator (placebo) for 6 months and followed for the next 2 years, with an MRI scan and clinical evaluation every 6 months. The main questions it aims to answer are if in the non-active stage of MS cladribine is potent to lessen brain volume loss and if it is potent to attenuate inflammation in the CNS.

Conditions

Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis

Keywords

Cladribine; Multiple Sclerosis Secondary Progressive; Brain Volume; Quantitative Susceptibility Mapping; Magnetic Resonance Imaging; Cognitive assessment

Outcome Measures

Primary Outcomes (2)

• Percent brain volume

  brain volume to total intracranial volume

  26 week following baseline

• Percent brain volume

  brain volume to total intracranial volume

  122 week following baseline

Secondary Outcomes (14)

• 24 weeks confirmed composite progression of disability

  96 week

• Symbol-Digit Modality Test

  26 week

• Symbol-Digit Modality Test

  96 week

• California Verbal Learning Test

  26 week

• California Verbal Learning Test

  122 week

Study Arms (2)

Experimental

EXPERIMENTAL

Drug: Cladribine at a dose of 1.8 mg/kg of body weight. Cladribine will be given subcutaneously over 6 visits every 5-6 weeks.

Drug: Cladribine Subcutaneous Injection

Control

PLACEBO COMPARATOR

Comparator: Placebo matched to the subcutaneous injection of cladribine.

Drug: 0.9% Chloride Injection Sodium

Interventions

Cladribine Subcutaneous Injection DRUG

Cladribine subcutaneous injection, 10 mg daily, for 2-3 consecutive days (depending on individual dose)

Also known as: Cladribine Solution

Experimental

0.9% Chloride Injection Sodium DRUG

0.9% sodium chloride injected subcutaneously, 10 ml daily, for 2-3 consecutive days

Control

Eligibility Criteria

• Age: 30 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Diagnosis of relapse-onset, secondary progressive multiple sclerosis based on the 2017 McDonald criteria
• Progression of disability over 24 months defined as an increase in the EDSS score of 1 or more for patients with EDSS ≤ 5.5 or of 0.5 or more for patients with EDSS \> 5.5
• Lack of relapses over last 12 months
• EDSS of 3.5 - 7.5 inclusive
• Age of 30 - 65 years inclusive
• Duration of MS of 10 years or longer
• Pre-menopausal women must refrain from heterosexual intercourse or use a contraception method with a failure rate of \< 1% from enrolment up to 6 months after the last dose of the investigational medicinal product
• Men must refrain from heterosexual intercourse from enrolment up to 6 months after the last dose of the investigational medicinal product or use a barrier method of contraception, with their female partners using a contraception method with a failure rate of \<1%
• Able to fulfill all protocol requirements as judged by the investigator

You may not qualify if:

• Lack of written informed consent
• Previous cladribine treatment
• Hypersensitivity to the investigational medicinal product
• Eligible and willing to use interferon beta, siponimod, or mitoxantrone
• Unable to undergo magnetic resonance imaging
• Pregnancy or breastfeeding
• Does not agree to use contraception methods defined above
• Diseases of the nervous system, such as tumors, stroke, traumatic injury, encephalomyelitis, B12 deficiency, or demyelinating diseases other than multiple sclerosis
• Major comorbidities, such as cancer, liver failure, kidney failure, heart failure (NYHA II-III), or any other disease that may jeopardize patient safety or make it impossible for the patient to fulfill protocol requirements
• Relapse within last 12 months
• Chronic treatment with corticosteroids or immunosuppressants (eg, azathioprine, methotrexate, cyclosporine) within last 6 months
• Disease-modifying treatments for multiple sclerosis (no washout is required for interferons beta, glatiramer acetate, and dimethyl fumarate; washout of \> 6 months for teriflunomide, fingolimod, and natalizumab \[an accelerate elimination procedure may be used for teriflunomide instead\]; washout of \> 12 months for ocrelizumab, mitoxantrone, and alemtuzumab)
• Relapsing-remitting multiple sclerosis
• Primary progressive multiple sclerosis
• Hepatitis B or hepatitis C, including detectable HbsA, anti-HBc, or anti-HCV antibodies in serum

Sponsors & Collaborators

• Institute of Psychiatry and Neurology, Warsaw: lead
• Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences: collaborator
• Mossakowski Medical Research Centre Polish Academy of Sciences: collaborator
• Poznan University of Medical Sciences: collaborator
• Military Institute of Aviation Medicine: collaborator

Study Sites (1)

Institute of Psychiatry and Neurology

Warsaw, Masovian Voivodeship, 02-957, Poland

RECRUITING

Related Publications (18)

• Lassmann H. Pathogenic Mechanisms Associated With Different Clinical Courses of Multiple Sclerosis. Front Immunol. 2019 Jan 10;9:3116. doi: 10.3389/fimmu.2018.03116. eCollection 2018.

  PMID: 30687321 BACKGROUND

• Jamroz-Wisniewska A, Beltowski J, Wojcicka G, Bartosik-Psujek H, Rejdak K. Cladribine Treatment Improved Homocysteine Metabolism and Increased Total Serum Antioxidant Activity in Secondary Progressive Multiple Sclerosis Patients. Oxid Med Cell Longev. 2020 Mar 14;2020:1654754. doi: 10.1155/2020/1654754. eCollection 2020.

  PMID: 32256946 BACKGROUND

• Fox RJ, Chataway J. Advancing trial design in progressive multiple sclerosis. Mult Scler. 2017 Oct;23(12):1573-1578. doi: 10.1177/1352458517729768.

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• Meinl E, Krumbholz M, Derfuss T, Junker A, Hohlfeld R. Compartmentalization of inflammation in the CNS: a major mechanism driving progressive multiple sclerosis. J Neurol Sci. 2008 Nov 15;274(1-2):42-4. doi: 10.1016/j.jns.2008.06.032. Epub 2008 Aug 19.

  PMID: 18715571 BACKGROUND

• Montalban X, Belachew S, Wolinsky JS. Ocrelizumab in Primary Progressive and Relapsing Multiple Sclerosis. N Engl J Med. 2017 Apr 27;376(17):1694. doi: 10.1056/NEJMc1702076. No abstract available.

  PMID: 28445663 BACKGROUND

• Comi G, Cook S, Giovannoni G, Rieckmann P, Sorensen PS, Vermersch P, Galazka A, Nolting A, Hicking C, Dangond F. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult Scler Relat Disord. 2019 Apr;29:168-174. doi: 10.1016/j.msard.2019.01.038. Epub 2019 Jan 24.

  PMID: 30885375 BACKGROUND

• Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet. 1997 Feb;32(2):120-31. doi: 10.2165/00003088-199732020-00003.

  PMID: 9068927 BACKGROUND

• Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E. Cladribine in treatment of chronic progressive multiple sclerosis. Lancet. 1994 Jul 2;344(8914):9-13. doi: 10.1016/s0140-6736(94)91046-4.

  PMID: 7912347 BACKGROUND

• Rejdak K, Stelmasiak Z, Grieb P. Cladribine induces long lasting oligoclonal bands disappearance in relapsing multiple sclerosis patients: 10-year observational study. Mult Scler Relat Disord. 2019 Jan;27:117-120. doi: 10.1016/j.msard.2018.10.006. Epub 2018 Oct 10.

  PMID: 30368223 BACKGROUND

• Jorgensen LO, Hyrlov KH, Elkjaer ML, Weber AB, Pedersen AE, Svenningsen AF, Illes Z. Cladribine modifies functional properties of microglia. Clin Exp Immunol. 2020 Sep;201(3):328-340. doi: 10.1111/cei.13473. Epub 2020 Jul 6.

  PMID: 32492189 BACKGROUND

• Montalban X, Gold R, Thompson AJ, Otero-Romero S, Amato MP, Chandraratna D, Clanet M, Comi G, Derfuss T, Fazekas F, Hartung HP, Havrdova E, Hemmer B, Kappos L, Liblau R, Lubetzki C, Marcus E, Miller DH, Olsson T, Pilling S, Selmaj K, Siva A, Sorensen PS, Sormani MP, Thalheim C, Wiendl H, Zipp F. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018 Feb;24(2):96-120. doi: 10.1177/1352458517751049. Epub 2018 Jan 20.

  PMID: 29353550 BACKGROUND

• Frischer JM, Weigand SD, Guo Y, Kale N, Parisi JE, Pirko I, Mandrekar J, Bramow S, Metz I, Bruck W, Lassmann H, Lucchinetti CF. Clinical and pathological insights into the dynamic nature of the white matter multiple sclerosis plaque. Ann Neurol. 2015 Nov;78(5):710-21. doi: 10.1002/ana.24497. Epub 2015 Aug 24.

  PMID: 26239536 BACKGROUND

• Hametner S, Wimmer I, Haider L, Pfeifenbring S, Bruck W, Lassmann H. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol. 2013 Dec;74(6):848-61. doi: 10.1002/ana.23974. Epub 2013 Oct 7.

  PMID: 23868451 BACKGROUND

• Dal-Bianco A, Grabner G, Kronnerwetter C, Weber M, Hoftberger R, Berger T, Auff E, Leutmezer F, Trattnig S, Lassmann H, Bagnato F, Hametner S. Slow expansion of multiple sclerosis iron rim lesions: pathology and 7 T magnetic resonance imaging. Acta Neuropathol. 2017 Jan;133(1):25-42. doi: 10.1007/s00401-016-1636-z. Epub 2016 Oct 27.

  PMID: 27796537 BACKGROUND

• Absinta M, Sati P, Masuzzo F, Nair G, Sethi V, Kolb H, Ohayon J, Wu T, Cortese ICM, Reich DS. Association of Chronic Active Multiple Sclerosis Lesions With Disability In Vivo. JAMA Neurol. 2019 Dec 1;76(12):1474-1483. doi: 10.1001/jamaneurol.2019.2399.

  PMID: 31403674 BACKGROUND

• Kaunzner UW, Kang Y, Zhang S, Morris E, Yao Y, Pandya S, Hurtado Rua SM, Park C, Gillen KM, Nguyen TD, Wang Y, Pitt D, Gauthier SA. Quantitative susceptibility mapping identifies inflammation in a subset of chronic multiple sclerosis lesions. Brain. 2019 Jan 1;142(1):133-145. doi: 10.1093/brain/awy296.

  PMID: 30561514 BACKGROUND

• Elliott C, Wolinsky JS, Hauser SL, Kappos L, Barkhof F, Bernasconi C, Wei W, Belachew S, Arnold DL. Slowly expanding/evolving lesions as a magnetic resonance imaging marker of chronic active multiple sclerosis lesions. Mult Scler. 2019 Dec;25(14):1915-1925. doi: 10.1177/1352458518814117. Epub 2018 Dec 19.

  PMID: 30566027 BACKGROUND

• Wang CT, Barnett M, Barnett Y. Imaging the multiple sclerosis lesion: insights into pathogenesis, progression and repair. Curr Opin Neurol. 2019 Jun;32(3):338-345. doi: 10.1097/WCO.0000000000000698.

  PMID: 30950846 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Iwona Kurkowska-Jastrzebska, MD, PhD

  Institute for Psychiatry and Neurology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Iwona Kurkowska-Jastrzebska, MD, PhD

CONTACT

+48-4582800; ikurkowska@ipin.edu.pl

Łukasz Smolinski, MD, PhD

CONTACT

+48-4582800; lsmolinski@ipin.edu.pl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2023
• First Posted: July 27, 2023
• Study Start: October 3, 2022
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): October 30, 2027
• Last Updated: July 28, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)