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

Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02442570
• Other study ID #: DC-002
• Status: Completed
• Phase: Phase 2
• First received: May 1, 2015
• Last updated: August 26, 2015
• Start date: September 2012
• Est. completion date: February 2015

Study information

• Verified date: May 2015
• Source: Delta Crystallon BV
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: February 2015
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Biological:
• recombinant human alpha B-crystallin
intravenous injections

Other:
• Placebo comparator
intravenous injection

Locations

Country	Name	City	State
Bulgaria	Aleksandrovska Hospital	Sofia
Bulgaria	Military Medical Academy	Sofia
Bulgaria	National Cardiology Hopsital	Sofia
Bulgaria	Sveti Naum Hospital	Sofia
Bulgaria	Tokuda Hospital Sofia	Sofia

Sponsors (1)

Lead Sponsor	Collaborator
Delta Crystallon BV

Country where clinical trial is conducted

Bulgaria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety (adverse events)	Frequency of adverse events	48 weeks	No
Secondary	Tolerability (Injection site abnormalities)	Injection site abnormalities	48 weeks	No
Secondary	Clinical efficacy (Number of Gadolinium-enhancing MRI lesions)	Number of Gadolinium-enhancing MRI lesions	48 weeks	No
Secondary	Pharmacokinetics (serum levels of DC-TAB)	Serum levels of DC-TAB	8 hours	No
Secondary	Antigen-specific T-cell response	Strength of antigen-specific T cell responses	48 weeks	No
Secondary	Antibody response	Serum levels of anti-DC-TAB antibodies	48 weeks	No