A Study to Evaluate Safety and Efficacy of DC-TAB in Multiple Sclerosis

A Phase IIa, Randomized, Double-blind, Placebo-controlled, Exploratory, Dose-ranging Study to Evaluate the Safety, Effectiveness and Pharmacokinetics of Three Courses of DC-TAB Treatment in Patients With Multiple Sclerosis

The purpose of this study is to evaluate safety and clinical efficacy of DC-TAB in multiple sclerosis.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Biological: recombinant human alpha B-crystallin; Other: Placebo comparator

Detailed Description

This study is a randomized, double-blind, placebo-controlled, exploratory, dose-ranging Phase IIa study in multiple sclerosis patients to evaluate the safety, tolerability, T-cell tolerance inducing effect, clinical effects and pharmacokinetics of intravenous DC-TAB, a solution of recombinant human alpha B-crystallin.

At entry, patients were randomized to one of the treatments, placebo, 7.5 mg DC-TAB, 12.5 mg DC-TAB or 17.5 mg DC-TAB in a 1:1:1:1 fashion. Patients received a single intravenous bolus injection which was repeated twice with 2-month intervals during the 6-month monitoring period. The goal of such injection was to induce antigen-specific T-cell tolerance. The study consisted of two parts, a treatment period of 24 weeks, and a follow-up period of an additional 24 weeks. Patients returned to the hospital weekly during the first month, and monthly thereafter.

The primary analysis was performed on data collected in the treatment period, and was performed after all patients had completed 24 weeks into the study. An additional analysis was performed once all patients had completed the full 48 weeks of the study. Patients and site study personnel remained blinded throughout the study.

After 12 and 24 patients completed 4 weeks into the study, and after 24 patients had completed 12 weeks of follow-up, a partially blinded safety review was conducted by an independent drug safety monitoring board to verify safety of the intervention in MS patients.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1431
    • Aleksandrovska Hospital
  • Sofia, Bulgaria, 1113
    • Sveti Naum Hospital
  • Sofia, Bulgaria, 1309
    • National Cardiology Hopsital
  • Sofia, Bulgaria, 1407
    • Tokuda Hospital Sofia
  • Sofia, Bulgaria, 1431
    • Military Medical Academy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Clinically definite relapsing multiple sclerosis, according to the McDonald criteria
2. Abnormal MRI consistent with MS
3. Neurologically stable for at least one month
4. At least one clinical relapse over the previous year, or two relapses over the past two years, or one or more gadolinium-enhancing MRI lesion(s) at the time of screening.
5. An EDSS score less than 6
6. Body weight less than 130 kg
7. Use of adequate and stable contraception for 3 months prior to study initiation, during the course of the study and 30 days thereafter or must have undergone clinically documented total hysterectomy and/or oophorectomy, surgical sterilization, or be postmenopausal defined by amenorrhea for at least 12 months and confirmed with a FSH greater than 40 mIU/mL.
8. If patients claim abstinence as their method of contraception, they must be willing to agree to use condoms if they became sexually active from 14 days prior to the first dose of the study drug through 90 days beyond the conclusion of the study.
9. Being informed of the nature and aims of the study, and having given written consent to participate in this study in accordance with local laws and requirements
10. Being willing to comply with the protocol, and understand the information given, and the text of the consent form

Exclusion Criteria:

1. Primary progressive multiple sclerosis
2. Use of systemic corticosteroid treatment for more than 3 days within 30 days prior to screening
3. Plasmapheresis, or intravenous gammaglobulins less than 2 months before screening
4. Treatment with natalizumab less than one year before screening
5. Previous immunosuppressive treatment
6. Previous treatment with any leukocyte-targeting monoclonal antibody
7. Previous treatment with oral immune-modulatory agents (cladribine, fingolimod, laquinimod, fumarate)
8. Pregnant women, women planning to become pregnant and breastfeeding women
9. A history of or currently active clinically significant cardiac (including clinically significant ECG abnormalities in the opinion of the PI), pulmonary, gastrointestinal, hepatic, renal, pancreatic, or neurological disease
10. ALT, AST and/or gamma-GT above 3 times the upper limit of normal
11. Serum creatinine above 1.5 times the upper limit of normal or an eGFR < 60 mL/min/1.73 m2
12. Hemoglobin < 7.0 mmol/l for females and < 8 mmol/l for males; leukocytes > 20*109/l or < 3.5*109/l; platelets < 125*109/l
13. SBP > 160 mmHg and/or DBP > 100 mmHg
14. Acute respiratory or other active infections
15. Fever (body temperature > 38.0 °C on day 1)
16. Blood donation or significant blood loss within 90 days of first study medication dosing
17. Plasma donation within 7 days of first study medication dosing
18. Having received blood or blood products in the last 6 months
19. Participation in another clinical study within 90 days of the start of this trial or planning participation in another clinical trial during this study or in the 4 weeks after last visit
20. Taking anti-coagulation or anti-platelet medication with the exception of NSAID's.
21. History of drug addiction (positive drug screen) or excessive use of alcohol (weekly intake more than 28 units of alcohol), or psychological or other emotional problems that are likely to invalidate informed consent, or limit the ability of the patient to comply with the protocol requirements
22. Vaccination with any vaccine within 4 weeks prior to dosing of the study medication
23. History of serious adverse reactions or hypersensitivity to any medicinal product
24. History of a malignancy other than skin cell basalioma 5 years prior to screening
25. Any physical condition that would, in the opinion of the investigator, place the patient at an unacceptable health risk or risk of injury or render the patient unable to meet the requirements of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: DC-TAB 7.5 mg; three intravenous injections of 7.5 mg DC-TAB (recombinant human alpha B-crystallin), 2 months apart	Biological: recombinant human alpha B-crystallin; intravenous injections; Other Names: HspB5; CRYAB; DC-TAB
Active Comparator: DC-TAB 12.5 mg; three intravenous injections of 12.5 mg DC-TAB (recombinant human alpha B-crystallin), 2 months apart	Biological: recombinant human alpha B-crystallin; intravenous injections; Other Names: HspB5; CRYAB; DC-TAB
Active Comparator: DC-TAB 17.5 mg; three intravenous injections of 17.5 mg DC-TAB (recombinant human alpha B-crystallin), 2 months apart	Biological: recombinant human alpha B-crystallin; intravenous injections; Other Names: HspB5; CRYAB; DC-TAB
Placebo Comparator: placebo; three intravenous injections of placebo, 2 months apart	Other: Placebo comparator; intravenous injection; Other Names: phosphate-buffered saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (adverse events)	Frequency of adverse events	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability (Injection site abnormalities)	Injection site abnormalities	48 weeks
Clinical efficacy (Number of Gadolinium-enhancing MRI lesions)	Number of Gadolinium-enhancing MRI lesions	48 weeks
Pharmacokinetics (serum levels of DC-TAB)	Serum levels of DC-TAB	8 hours
Antigen-specific T-cell response	Strength of antigen-specific T cell responses	48 weeks
Antibody response	Serum levels of anti-DC-TAB antibodies	48 weeks

Collaborators and Investigators

• Sponsor: Delta Crystallon BV
• Investigators: Study Director: Lilly Boneva, MSc, Population Services International

Publications and helpful links

General Publications

• van Noort JM, Bsibsi M, Nacken PJ, Verbeek R, Venneker EH. Therapeutic Intervention in Multiple Sclerosis with Alpha B-Crystallin: A Randomized Controlled Phase IIa Trial. PLoS One. 2015 Nov 23;10(11):e0143366. doi: 10.1371/journal.pone.0143366. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: September 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: May 1, 2015
• First Submitted That Met QC Criteria: May 12, 2015
• First Posted (Estimate): May 13, 2015

Study Record Updates

• Last Update Posted (Estimate): August 27, 2015
• Last Update Submitted That Met QC Criteria: August 26, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: alpha B-crystallin; immune tolerance
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: DC-002