Multiple SclerosisPhase 1/2CAM-THYNCT01712945
Keratinocyte Growth Factor to Prevent Autoimmunity After Alemtuzumab Treatment of Multiple Sclerosis
A Phase 1/2 study testing Palifermin and Alemtuzumab in people with Multiple Sclerosis, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
The purpose of this study is to test a novel strategy to prevent the clinical problem of secondary autoimmunity following alemtuzumab treatment of multiple sclerosis. The hypothesis is that autoimmunity after alemtuzumab can be prevented by giving a drug that promotes thymic T cell regeneration (Palifermin… Read more about this study
- Who is it for?
- Ages 18 months to 50 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Palifermin and Alemtuzumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2012to Oct 2017
- Phase
- Phase 1/2
- 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 months to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Male or non-pregnant, non-lactating female patients
- > 18 years of age, and <50 years of age inclusive
- Diagnosis of MS using McDonald's 2010 criteria, including MRI abnormalities consistent with McDonald's 2010 criteria.
- Onset of first MS symptoms within 10 years on the date the ICF is signed
- EDSS score 0.0 to 5.0 (inclusive) at screening
- At least 2 clinical episodes of MS in the 2 years prior to study entry, with at least 1 attack within 12 months, which may have occurred whilst on disease-modifying therapy, namely any beta interferon or glatiramer acetate.
- Serum IL-7≤7pg/mL
Who cannot join
- Any progressive form of multiple sclerosis
- Previous thymectomy
- Previous treatment with alemtuzumab, natalizumab, mitoxantrone, cyclophosphomide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids and disease-modifying therapies listed above)
- History of malignancy
- Personal history of clinically significant autoimmune disease, other than multiple sclerosis (including but not limited to: thyroid disease, immune cytopenias, inflammatory bowel disease, diabetes, lupus, severe asthma)
- Intolerance of pulsed corticosteroids, especially a history of steroid psychosis
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- Major systemic disease or other illness that would, in the opinion of the investigator, compromise patient safety or interfere with the interpretation of study results.
- Seropositivity for human immunodeficiency virus (HIV)
- Past or present hepatitis B infection (positive hepatitis B serology)
- Pregnant women or male and female patients who do not agree to use effective contraception during the study.
- Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Addenbrooke's Hospital
Cambridge, Cambridgeshire, CB2 2QQ
About this study
Official title: Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis
The purpose of this study is to test a novel strategy to prevent the clinical problem of secondary autoimmunity following alemtuzumab treatment of multiple sclerosis.
The hypothesis is that autoimmunity after alemtuzumab can be prevented by giving a drug that promotes thymic T cell regeneration (Palifermin, Kepivance®).
Read the detailed description
This is a single-centre, double-blinded, randomised controlled trial of palifermin (Kepivance) vs. placebo in the prevention of autoimmunity following alemtuzumab treatment of multiple sclerosis.
The dose of palifermin (kepivance)used in this trial will be informed by a dose-escalation study.
- Conditions
- Multiple Sclerosis
- Being tested
- Palifermin, Alemtuzumab
- Keywords
- Alemtuzumab, Palifermin, Reconstitution, Thymus
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PaliferminDrug
Also called Kepivance, keratinocyte growth factor
Palifermin (Kepivance®) administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose.
AlemtuzumabDrug
Also called Campath-1H
Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day).
| Study group | Role | What they receive |
|---|---|---|
| Palifermin (and Alemtuzumab) | Experimental | Palifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). Receives: Drug: Palifermin; Drug: Alemtuzumab |
| Placebo (and Alemtuzumab) | Placebo comparator | Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). Receives: Drug: Alemtuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
incidence of clinical autoimmunity
The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab
Measured: within 30 months of starting treatment with alemtuzumab
Secondary outcomes (2)
Absolute numbers of naive T cells
Absolute numbers of naive T cells
Measured: within 30 months of starting treatment with alemtuzumab
Safety events
Safety outcomes - incidence and nature of adverse events
Measured: within 30 months of starting treatment with alemtuzumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2012 (estimated)
- Study startJun 2012
- Primary completionAug 2017
- Study completionOct 2017
Why it stopped: interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)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 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cambridge University Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alasdair Coles, Cambridge University Hospitals NHS Foundation Trust
- Investigators
- Alasdair Coles, Phd FRCP, Principal investigator, University of Cambridge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01712945
- Sponsor's protocol ID
- EudraCT 2011-005606-30
- Acronym
- CAM-THY
- Status last verified
- Apr 2019
- First submitted
- 19 Oct 2012
- Last updated
- 30 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011 Apr;10(4):338-48. doi: 10.1016/S1474-4422(11)70020-5.
PubMed 21397567Jones JL, Phuah CL, Cox AL, Thompson SA, Ban M, Shawcross J, Walton A, Sawcer SJ, Compston A, Coles AJ. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Invest. 2009 Jul;119(7):2052-61. doi: 10.1172/JCI37878. Epub 2009 Jun 22.
PubMed 19546505Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005 Nov;35(11):3332-42. doi: 10.1002/eji.200535075.
PubMed 16231285CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
PubMed 18946064Bruinsma M, van Soest PL, Leenen PJ, Lambrecht BN, Cupedo T, Lowenberg B, Cornelissen JJ, Braakman E. Keratinocyte growth factor induces expansion of murine peripheral CD4+Foxp3+ regulatory T cells and increases their thymic output. J Immunol. 2007 Dec 1;179(11):7424-30. doi: 10.4049/jimmunol.179.11.7424.
PubMed 18025186Miller RD, Caulfield MJ, Calkins CE. Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice. J Immunol. 1992 Apr 15;148(8):2452-5.
PubMed 1560201Min D, Panoskaltsis-Mortari A, Kuro-O M, Hollander GA, Blazar BR, Weinberg KI. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007 Mar 15;109(6):2529-37. doi: 10.1182/blood-2006-08-043794. Epub 2006 Nov 30.
PubMed 17138819Coles AJ, Azzopardi L, Kousin-Ezewu O, Mullay HK, Thompson SA, Jarvis L, Davies J, Howlett S, Rainbow D, Babar J, Sadler TJ, Brown JWL, Needham E, May K, Georgieva ZG, Handel AE, Maio S, Deadman M, Rota I, Hollander G, Dawson S, Jayne D, Seggewiss-Bernhardt R, Douek DC, Isaacs JD, Jones JL. Keratinocyte growth factor impairs human thymic recovery from lymphopenia. JCI Insight. 2019 May 7;5(12):e125377. doi: 10.1172/jci.insight.125377.
PubMed 31063156
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Keratinocyte Growth Factor - Promoting Thymic Reconstitution and Preventing Autoimmunity After Alemtuzumab (Campath-1H) Treatment of Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01712945
- Acronym / sponsor ID
- CAM-THY / EudraCT 2011-005606-30
- Conditions
- Multiple Sclerosis
- Keywords
- Alemtuzumab, Palifermin, Reconstitution, Thymus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Cambridge University Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- Jun 2012 (actual)
- Primary completion
- Aug 2017 (actual)
- Study completion
- Oct 2017 (actual)
- First posted
- 24 Oct 2012 (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 test a novel strategy to prevent the clinical problem of secondary autoimmunity following alemtuzumab treatment of multiple sclerosis.
The hypothesis is that autoimmunity after alemtuzumab can be prevented by giving a drug that promotes thymic T cell regeneration (Palifermin, Kepivance®).
Detailed description
This is a single-centre, double-blinded, randomised controlled trial of palifermin (Kepivance) vs. placebo in the prevention of autoimmunity following alemtuzumab treatment of multiple sclerosis.
The dose of palifermin (kepivance)used in this trial will be informed by a dose-escalation study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Palifermin (and Alemtuzumab) | Experimental | Drug: Palifermin, Drug: AlemtuzumabPalifermin (Kepivance®), at the maximum identified tolerated dose will be administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. Initial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). |
| Placebo (and Alemtuzumab) | Placebo comparator | Drug: AlemtuzumabInitial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). |
Who may qualify
- Ages
- 18 months to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Male or non-pregnant, non-lactating female patients
- > 18 years of age, and <50 years of age inclusive
- Diagnosis of MS using McDonald's 2010 criteria, including MRI abnormalities consistent with McDonald's 2010 criteria.
- Onset of first MS symptoms within 10 years on the date the ICF is signed
- EDSS score 0.0 to 5.0 (inclusive) at screening
Key exclusion criteria (11 listed)
- Any progressive form of multiple sclerosis
- Previous thymectomy
- Previous treatment with alemtuzumab, natalizumab, mitoxantrone, cyclophosphomide, cladribine, rituximab or any other immunosuppressant or cytotoxic therapy (other than steroids and disease-modifying therapies listed above)
- History of malignancy
- Personal history of clinically significant autoimmune disease, other than multiple sclerosis (including but not limited to: thyroid disease, immune cytopenias, inflammatory bowel disease, diabetes, lupus, severe asthma)
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 |
|---|---|---|
| PaliferminAlso: Kepivance, keratinocyte growth factorPalifermin (Kepivance®) administered by intravenous bolus on days -5, -4. -3 prior to, and on days 8, 9 and 10 after each cycle of alemtuzumab, then again on 3 consecutive days at month 1 and month 3 after each cycle of alemtuzumab. Patients will be observed for adverse reactions for at least 1 to 2 hours following each bolus dose. | Drug | Palifermin (and Alemtuzumab) |
| AlemtuzumabAlso: Campath-1HInitial treatment alemtuzumab will be administered as a fixed total dose of 60 mg IV over 5 consecutive days (12mg/day). For re-treatment at Month 12, alemtuzumab will be administered as a fixed total dose of 36mg IV over 3 consecutive days (12mg/day). | Drug | Palifermin (and Alemtuzumab), Placebo (and Alemtuzumab) |
Primary outcome
incidence of clinical autoimmunity
Time frame: within 30 months of starting treatment with alemtuzumab
The primary endpoint is incidence of clinical autoimmunity within 30 months of starting treatment with alemtuzumab
2 secondary outcomes
Absolute numbers of naive T cells
Time frame: within 30 months of starting treatment with alemtuzumab
Safety events
Time frame: within 30 months of starting treatment with alemtuzumab
Results and safety
The study was stopped early (reason given: interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2019.
- Background: PubMed 21397567Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Bass AD, Wynn DR, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA. Alemtuzumab versus interferon beta-1a in early relapsing-remitting multiple sclerosis: post-hoc and subset analyses of clinical efficacy outcomes. Lancet Neurol. 2011 Apr;10(4):338-48. doi: 10.1016/S1474-4422(11)70020-5.
- Background: PubMed 19546505Jones JL, Phuah CL, Cox AL, Thompson SA, Ban M, Shawcross J, Walton A, Sawcer SJ, Compston A, Coles AJ. IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H). J Clin Invest. 2009 Jul;119(7):2052-61. doi: 10.1172/JCI37878. Epub 2009 Jun 22.
- Background: PubMed 16231285Cox AL, Thompson SA, Jones JL, Robertson VH, Hale G, Waldmann H, Compston DA, Coles AJ. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur J Immunol. 2005 Nov;35(11):3332-42. doi: 10.1002/eji.200535075.
- Background: PubMed 18946064CAMMS223 Trial Investigators; Coles AJ, Compston DA, Selmaj KW, Lake SL, Moran S, Margolin DH, Norris K, Tandon PK. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N Engl J Med. 2008 Oct 23;359(17):1786-801. doi: 10.1056/NEJMoa0802670.
- Background: PubMed 18025186Bruinsma M, van Soest PL, Leenen PJ, Lambrecht BN, Cupedo T, Lowenberg B, Cornelissen JJ, Braakman E. Keratinocyte growth factor induces expansion of murine peripheral CD4+Foxp3+ regulatory T cells and increases their thymic output. J Immunol. 2007 Dec 1;179(11):7424-30. doi: 10.4049/jimmunol.179.11.7424.
- Background: PubMed 1560201Miller RD, Caulfield MJ, Calkins CE. Expression and regulation of a recurrent anti-erythrocyte autoantibody idiotype in spleen cells from neonatal and adult BALB/c mice. J Immunol. 1992 Apr 15;148(8):2452-5.
- Background: PubMed 17138819Min D, Panoskaltsis-Mortari A, Kuro-O M, Hollander GA, Blazar BR, Weinberg KI. Sustained thymopoiesis and improvement in functional immunity induced by exogenous KGF administration in murine models of aging. Blood. 2007 Mar 15;109(6):2529-37. doi: 10.1182/blood-2006-08-043794. Epub 2006 Nov 30.
- Derived from this study: PubMed 31063156Coles AJ, Azzopardi L, Kousin-Ezewu O, Mullay HK, Thompson SA, Jarvis L, Davies J, Howlett S, Rainbow D, Babar J, Sadler TJ, Brown JWL, Needham E, May K, Georgieva ZG, Handel AE, Maio S, Deadman M, Rota I, Hollander G, Dawson S, Jayne D, Seggewiss-Bernhardt R, Douek DC, Isaacs JD, Jones JL. Keratinocyte growth factor impairs human thymic recovery from lymphopenia. JCI Insight. 2019 May 7;5(12):e125377. doi: 10.1172/jci.insight.125377.
- Information for patients on protocolLink provided by the sponsor.
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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.
Alasdair Coles, Phd FRCP principal investigator
University of Cambridge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Palifermin and Alemtuzumab in people with Multiple Sclerosis, run by Cambridge University Hospitals NHS Foundation Trust at 1 site in United Kingdom.
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 11 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: stopped early, as of the sponsor's last update on 30 Apr 2019. 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 United Kingdom. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: interim anlaysis failed: palifermin does not promote thymopoeisis after alemtuzumab). Results are not available in the source record.
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?
incidence of clinical autoimmunity (time frame: within 30 months of starting treatment with alemtuzumab). 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 NCT01712945, which also lists 8 linked publications.
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 30 Apr 2019.