Multiple SclerosisPhase 1NCT02442557
Safety and Dose-finding Study of DC-TAB in Healthy Subjects
A Phase 1 study testing recombinant human alpha B-crystallin in people with Multiple Sclerosis, run by Delta Crystallon BV at 1 site in Netherlands.
Trial summary
The purpose of this study is to determine safety and appropriate dose of DC-TAB for selective immune tolerance induction in humans. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- recombinant human alpha B-crystallin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 76 participants
- Where
- 1 siteNetherlands
- Study dates
- Dec 2009to Jul 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Caucasian
- Signed the written informed consent form before first screening procedure
- Age ≥ 18 years and ≤ 55 years
- In general good health in the opinion of the investigator
- BMI between 20.0 and 28.0 kg/m2
- Use of adequate and stable contraception for 3 months prior to study initiation, during the course of the study and 30 days thereafter. Sexually active males must use a condom. Sexually active females must use double-barrier contraception or hormonal contraceptive (oral, transdermal, vaginal ring, implants), 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 higher than 40 IU/mL.
- If subjects claim abstinence as their method of contraception, they must be willing to agree to use condoms if they become sexually active from 14 days prior to the first dose of the study drug through 90 days beyond the conclusion of the study.
Who cannot join
- Pregnant women, women planning to become pregnant and breastfeeding women
- Subjects with a history of MS in first grade family members
- 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
- ALT, AST and/or gamma-GT above 3 times the upper limit of normal
- Serum creatinine above 1.5 times the upper limit of normal
- Amylase above 1.5 times the upper limit of normal
Show all 26Show fewer
- Hemoglobin < 7.0 mmol/L for females and < 8 mmol/L for males; leucocytes > 20*109/L or < 3.5*109/L; platelets < 125*109/L
- SBP > 160 mmHg and/or DBP > 100 mmHg
- Known or suspected hypersensitivity to any component of DC-TAB
- Known or suspected impairment of the immune system
- Acute respiratory or other active infections or illnesses
- Fever (oral temperature > 38.0 °C on day 1)
- Blood donation or significant blood loss within 90 days of first study medication dosing.
- Plasma donation within 7 days of first study medication dosing
- Recipients of blood or blood products in the last 6 months
- 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
- Taking immunosuppressive agents, corticosteroids, anti-allergic, anti-coagulation or anti-platelet medication
- 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 subject to comply with the protocol requirements
- Positive HIV1, or HIV2 serology
- Positive results from the hepatitis serology which indicates acute or chronic hepatitis B or hepatitis C
- Positive alcohol breath test
- Vaccination with any vaccine within 4 weeks prior to dosing of the study medication
- Any physical condition that would, in the opinion of the investigator, place the subject at an unacceptable health risk or risk of injury or render the subject unable to meet the requirements of the protocol
- History of serious adverse reactions or hypersensitivity to any medicinal product
- Smoking > 5 cigarettes/day or unable to refrain from smoking while confined to the CPU
- Use of prescription, over-the-counter (OTC), herbal supplements (excluding hormonal contraceptives, one-a-day vitamins, acetaminophen) within 14 days prior to the first dose of study drug).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and T-cell Tolerizing Effect of DC-TAB in Healthy Volunteers
The purpose of this study is to determine safety and appropriate dose of DC-TAB for selective immune tolerance induction in humans.
Read the detailed description
This study is a double-blind, randomized, placebo-controlled, dose-escalation study of DC-TAB in healthy human volunteers. DC-TAB is a solution of the small heat-shock protein alpha B-crystallin for intravenous injection, designed to induce selective immunological tolerance as a treatment for multiple sclerosis. In this first-in-man study, DC-TAB is administered to healthy subjects in varying doses and for a varying number of times, after which safety and tolerability is evaluated, as well as the impact of the treatment on antigen-specific responses by peripheral blood T cells and serum antibodies. Blood samples are additionally collected to measure serum concentrations of DC-TAB, and to determine the rate of clearance from the circulation. The study is double blind and placebo-controlled to strengthen the significance especially of immunological evaluations.
The study consists of two parts. In Part 1, subjects receive a single dose of DC-TAB or placebo whereas in Part 2, (different) subjects receive DC-TAB or placebo on 3 consecutive days. In Part 1, four groups of subjects (n=10) are studied in a single dose, dose-escalation design. Each group of subjects are randomized to receive either DC-TAB (n=8) or placebo (n=2) once. In Part 2, three groups of subjects (n=12) are studied in a multiple dose, dose-escalation design. Each group of subjects are randomized to receive either DC-TAB (n=9) or placebo (n=3) once daily on 3 consecutive days. The next higher dose group in each part of the study only starts once safety data up to 4 days for Part 1, up to 8 days for Part 2 of the previous dose group have been reviewed and have raised no safety concerns. Part 2 is started once all safety data of Part 1 have been reviewed. Immunological effects of the treatments are evaluated over a period of 28 days.
- Conditions
- Multiple Sclerosis
- Being tested
- recombinant human alpha B-crystallin, placebo comparator
- Keywords
- alpha B-crystallin, immune tolerance
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
recombinant human alpha B-crystallinBiological
Also called HspB5; CRYAB; DC-TAB
intravenous injection
placebo comparatorOther
Also called phosphate-buffered saline
intravenous injection
| Study group | Role | What they receive |
|---|---|---|
| single dose 4 mg | Active comparator | a single intravenous injection of 4 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| single dose 12.5 mg | Active comparator | a single intravenous injection of 12.5 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| single dose 25 mg | Active comparator | a single intravenous injection of 25 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| single dose 37.5 mg | Active comparator | a single intravenous injection of 4 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| single dose placebo | Placebo comparator | a single intravenous injection of placebo Receives: Other: placebo comparator |
| multiple dose 10 mg | Active comparator | three consecutive daily intravenous injections of 10 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| multiple dose 25 mg | Active comparator | three consecutive daily intravenous injections of 25 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| multiple dose 37.5 mg | Active comparator | three consecutive daily intravenous injections of 37.5 mg DC-TAB Receives: Biological: recombinant human alpha B-crystallin |
| multiple dose placebo | Placebo comparator | three consecutive daily intravenous injections of placebo Receives: Other: placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety (adverse events)
Frequency of
Measured: 28 days
Secondary outcomes (4)
Antigen-specific T-cell response
Strength of antigen-specific T-cell responses
Measured: 28 days
Pharmacokinetics (serum levels of DC-TAB)
Serum levels of DC-TAB
Measured: 24 h
Local tolerability (Injection site abnormalities)
Injection site abnormalities
Measured: 28 days
Antibody responses
Serum levels of anti-DC-TAB antibodies
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2015 (estimated)
- Study startDec 2009
- Primary completionOct 2010
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Delta Crystallon BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Floris Höppener, PhD, MD, Principal investigator, Syneos Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02442557
- Sponsor's protocol ID
- DC-001
- Status last verified
- May 2015
- First submitted
- 1 May 2015
- Last updated
- 13 May 2015
- Results posted
- No
- Data monitoring committee
- No
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.
PubMed 26599332
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and T-cell Tolerizing Effect of DC-TAB in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02442557
- Acronym / sponsor ID
- DC-001
- Conditions
- Multiple Sclerosis
- Keywords
- alpha B-crystallin, immune tolerance
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Delta Crystallon BVIndustry (pharma, biotech, devices)
- Study start
- Dec 2009
- Primary completion
- Oct 2010 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 13 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine safety and appropriate dose of DC-TAB for selective immune tolerance induction in humans.
Detailed description
This study is a double-blind, randomized, placebo-controlled, dose-escalation study of DC-TAB in healthy human volunteers. DC-TAB is a solution of the small heat-shock protein alpha B-crystallin for intravenous injection, designed to induce selective immunological tolerance as a treatment for multiple sclerosis. In this first-in-man study, DC-TAB is administered to healthy subjects in varying doses and for a varying number of times, after which safety and tolerability is evaluated, as well as the impact of the treatment on antigen-specific responses by peripheral blood T cells and serum antibodies. Blood samples are additionally collected to measure serum concentrations of DC-TAB, and to determine the rate of clearance from the circulation. The study is double blind and placebo-controlled to strengthen the significance especially of immunological evaluations.
The study consists of two parts. In Part 1, subjects receive a single dose of DC-TAB or placebo whereas in Part 2, (different) subjects receive DC-TAB or placebo on 3 consecutive days. In Part 1, four groups of subjects (n=10) are studied in a single dose, dose-escalation design. Each group of subjects are randomized to receive either DC-TAB (n=8) or placebo (n=2) once. In Part 2, three groups of subjects (n=12) are studied in a multiple dose, dose-escalation design. Each group of subjects are randomized to receive either DC-TAB (n=9) or placebo (n=3) once daily on 3 consecutive days. The next higher dose group in each part of the study only starts once safety data up to 4 days for Part 1, up to 8 days for Part 2 of the previous dose group have been reviewed and have raised no safety concerns. Part 2 is started once all safety data of Part 1 have been reviewed. Immunological effects of the treatments are evaluated over a period of 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| single dose 4 mg | Active comparator | Biological: recombinant human alpha B-crystallina single intravenous injection of 4 mg DC-TAB |
| single dose 12.5 mg | Active comparator | Biological: recombinant human alpha B-crystallina single intravenous injection of 12.5 mg DC-TAB |
| single dose 25 mg | Active comparator | Biological: recombinant human alpha B-crystallina single intravenous injection of 25 mg DC-TAB |
| single dose 37.5 mg | Active comparator | Biological: recombinant human alpha B-crystallina single intravenous injection of 4 mg DC-TAB |
| single dose placebo | Placebo comparator | Other: placebo comparatora single intravenous injection of placebo |
| multiple dose 10 mg | Active comparator | Biological: recombinant human alpha B-crystallinthree consecutive daily intravenous injections of 10 mg DC-TAB |
| multiple dose 25 mg | Active comparator | Biological: recombinant human alpha B-crystallinthree consecutive daily intravenous injections of 25 mg DC-TAB |
| multiple dose 37.5 mg | Active comparator | Biological: recombinant human alpha B-crystallinthree consecutive daily intravenous injections of 37.5 mg DC-TAB |
| multiple dose placebo | Placebo comparator | Other: placebo comparatorthree consecutive daily intravenous injections of placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Caucasian
- Signed the written informed consent form before first screening procedure
- Age ≥ 18 years and ≤ 55 years
- In general good health in the opinion of the investigator
- BMI between 20.0 and 28.0 kg/m2
Key exclusion criteria (26 listed)
- Pregnant women, women planning to become pregnant and breastfeeding women
- Subjects with a history of MS in first grade family members
- 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
- ALT, AST and/or gamma-GT above 3 times the upper limit of normal
- Serum creatinine above 1.5 times the upper limit of normal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| recombinant human alpha B-crystallinAlso: HspB5; CRYAB; DC-TABintravenous injection | Biological | multiple dose 10 mg, multiple dose 25 mg, multiple dose 37.5 mg, single dose 12.5 mg, single dose 25 mg, single dose 37.5 mg, single dose 4 mg |
| placebo comparatorAlso: phosphate-buffered salineintravenous injection | Other | multiple dose placebo, single dose placebo |
Primary outcome
Safety (adverse events)
Time frame: 28 days
Frequency of
4 secondary outcomes
Antigen-specific T-cell response
Time frame: 28 days
Pharmacokinetics (serum levels of DC-TAB)
Time frame: 24 h
Local tolerability (Injection site abnormalities)
Time frame: 28 days
Antibody responses
Time frame: 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 May 2015.
- Derived from this study: PubMed 26599332van 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Floris Höppener, PhD, MD principal investigator
Syneos Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing recombinant human alpha B-crystallin in people with Multiple Sclerosis, run by Delta Crystallon BV at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (adverse events) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02442557, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 May 2015.