ATX-MS-1467 in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

An Open-label, One-arm, Baseline-controlled Proof of Concept Trial to Evaluate the Safety of ATX-MS-1467 and Its Effect on Immune Tolerance in Subjects With Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01973491
• Other study ID #: 200166-001
• Secondary ID: 2013-002916-28
• Status: Completed
• Phase: Phase 2
• First received: October 23, 2013
• Last updated: August 9, 2016
• Start date: February 2014
• Est. completion date: May 2016

Study information

• Verified date: August 2016
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian FederationLatvia: State Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, open-label, single arm, baseline-controlled Phase 2a trial to evaluate the clinical and biological effects of ATX-MS-1467 in subjects with relapsing multiple sclerosis (MS) and to assess the maintenance of any such effects.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: May 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Male or female out-patients aged 18 to 65 years of age inclusive at the time of informed consent

• Willing and able to provide written informed consent and to comply with the requirements of the protocol assessments/procedures

• Relapsing MS (relapsing-remitting multiple sclerosis [RRMS], secondary progressive multiple sclerosis [SPMS], as defined by the revised McDonald criteria [2010]) (11)

• Clinical evidence of recent MS activity and radiological activity on gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) defined as defined in the protocol

• Expanded disability status scale (EDSS) score 0-5.5

• Human leukocyte antigen-beta chain (HLA-DRB)1*15 positive

• Neurological stability in the 30 days prior to Visit 5 (Study Day 1)

• Prior vaccination against tuberculosis (TB)

• If female, unless post-menopausal (for at least 2 years) or surgically sterilized, must be willing to use two highly effective methods of contraception throughout the entire duration of the trial and for 90 days following the last dose of ATX-MS-1467

• If male, must be willing to use two highly effective methods of contraception throughout the entire duration of the trial and for 90 days following the last dose of ATX-MS-1467

Exclusion Criteria:

• Primary progressive MS

• Inability to comply with MRI scanning, including contra-indications to MRI such as known allergy to gadolinium contrast dyes, claustrophobia, presence of a pacemaker, cochlear implants, ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, nerve stimulators

• Previous treatment with beta-interferon, plasma exchange, intravenous gamma globulin within the 8 weeks prior to study Day 1 (Visit 5), steroids (administered via the oral and/or parenteral routes) or adrenocorticotropic hormone within the 30 days prior to the Visit 2 MRI scan, glatiramer acetate, cytotoxic agents

• Prior exposure to dimethyl fumurate (BG-12) or dirucotide, any disease-related T cell vaccine or peptide-tolerizing agent for the treatment of MS, including ATX-MS-1467

• Use of any investigational drug or experimental procedure for MS (including cytokine or anticytokine therapy) within the 30 days prior to screening (Visit 1)

• Inadequate liver function as defined in the protocol.

• Lymphocyte count less than (<)500 per micro liter (/mcL) or neutrophil count < 1500 mcL at screening or at any of the pre-treatment visits (Visits 2-4)

• Major medical illness as defined in the protocol

• Known history of active or chronic infectious disease or any disease which compromises immune function

• Any renal condition that would preclude the administration of gadolinium

• History of malignancy, including both solid tumor and hematological malignancies, but excluding basal cell and in situ squamous cell carcinomas of the skin that have been excised and resolved, in situ cervical cancer or prostatic cancer with normal prostatic specific antigen

• Clinical evidence of severe uncontrolled depression, active suicidal ideation or suicide attempt

• Any other significant medical or psychiatric conditions that, in the opinion of the Investigator, would preclude participation in the trial or impair the ability to give informed consent

• Major surgery in the 4 weeks prior to screening (Visit 1)

• Known hypersensitivity to the trial medication or diluents

• Participation in another clinical trial within the 30 days prior to screening (Visit 1)

• Pregnancy, lactation or a positive pregnancy test during screening (urine dipstick) or at Visit 4 (serum beta-human chorionic gonadotrophin [beta-hCG]), or intention to become pregnant or to breast-feed during the course of the trial

• Legal incapacity or limited legal capacity

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• ATX-MS-1467
ATX-MS-1467 will be administered as per dosage regimen specified in the protocol for 4 weeks (dose titration period) followed by 16 weeks of treatment, and 16 additional weeks of observation.

Locations

Country	Name	City	State
Germany	Please contact the Merck KGaA Communication Center	Darmstadt

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the average number of time constant 1 (T1) contrast-enhanced lesions (CEL) at three on-treatment scans (Weeks 12, 16 and 20) compared to the average number of T1 CEL at three Baseline scans (Weeks -8, -4 and 0)		Weeks -8, -4, 0, 12, 16 and 20	No
Secondary	Number of T1 CEL		Weeks 12, 16, 20, 24, 28 and 36	No
Secondary	Change from Baseline (average of 3 Baseline scans, Weeks -8, -4 and 0) in total number of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36		Weeks -8, -4, 0, 12, 16, 20, 24, 28 and 36	No
Secondary	Change from Baseline (average of 3 Baseline scans, Weeks -8, -4 and 0) in total volume of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36		Weeks -8, -4, 0, 12, 16, 20, 24, 28 and 36	No
Secondary	Number of new or newly enlarging time constant 2 (T2) lesions		Weeks 12, 16, 20, 24, 28 and 36	No
Secondary	Change from Baseline (Week 0) in total number of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36		Weeks 0, 12, 16, 20, 24, 28 and 36	No
Secondary	Change from Baseline (Week 0) in total volume of T1 CEL at Weeks 12, 16, 20, 24, 28 and 36		Weeks 0, 12, 16, 20, 24, 28 and 36	No
Secondary	Mean Annualized Relapse Rate		Week 20	No
Secondary	Time to first relapse		Baseline up to Week 36	No
Secondary	Change from Baseline (Week 0) in total expanded disability status scale (EDSS) score at Week 20		Week 0 and Week 20	No
Secondary	Change from Baseline (Week 0) in total multiple sclerosis functional composite (MSFC) score at Week 20		Week 0 and Week 20	No
Secondary	Change from Baseline (Week 0) in myelin basic protein (MBP)-induced peripheral blood mononuclear cells (PBMC) proliferation at Week 20		Week 0 and Week 20	No
Secondary	Change from Week 20 in MBP-PBMC proliferation at Week 36		Week 20 and Week 36	No
Secondary	Number of subjects with treatment-emergent adverse events (TEAEs)		Baseline up to Week 36	Yes
Secondary	Number of subjects experiencing injection site reactions (ISRs)		Baseline up to Week 24	Yes