Systemic SclerosisPhase 2NCT00769028
AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis
A Phase 2 study testing Hyperimmune caprine serum and Albumin in people with Systemic Sclerosis, run by Daval International Limited at 1 site in United Kingdom.
Trial summary
To study the safety and tolerability of a hyperimmune goat serum product (AIMSPRO) in the treatment of systemic sclerosis (SSc) through a period of 26 weeks of study participation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis
- What is being tested?
- Hyperimmune caprine serum and Albumin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2008to Sep 2011
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must fulfill 1980 Preliminary Classification Criteria for systemic sclerosis of the American Rheumatism Association
- Diffuse cutaneous SSc, as evidenced by skin sclerosis proximal to the elbows or knees and absence of the anti-centromere autoantibody
- At least three years must have elapsed since the first non-Raynaud's manifestation
- Men and women of childbearing potential must use adequate birth control measures for the duration of the study and should continue such precautions for six months after receiving the last injection of AIMSPRO.
- Screening laboratory test results:
- Hemoglobin > 8.5 g/dL WBC > 3.5 x 10^9/L Neutrophils > 1.5 x 10^9/L Platelets > 100 x 10^9/L SGOT (AST) and alkaline phosphatase levels must be within twice the upper limit of normal range for the laboratory conducting the test.
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- Patient must be able to adhere to the study visit schedule and other protocol requirements
- Patient must be capable of giving informed consent and the consent must be obtained prior to any screening procedures
- No radiological evidence of malignancy, infection or (previous) tuberculosis in a chest radiograph performed within three months prior to the first injection of study drug
Who cannot join
- Women who are pregnant, nursing, or planning pregnancy within one and a half years after screening (i.e., approximately six months following last injection of study drug).
- Use of any investigational drug within one month prior to screening or within five half-lives of the investigational agent, whichever is longer.
- Use of a putative disease modifying drug (potential immunosuppressive drug) within one month of screening.
- Treatment with any therapeutic agent targeted at reducing TNF (e.g., infliximab, pentoxifylline, thalidomide, etanercept, etc.) within three months of screening.
- Previous administration of AIMSPRO.
- History of known allergy to animal proteins.
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- Serious infections (such as pneumonia or pyelonephritis) in the previous three months. Less serious infections (such as acute upper respiratory tract infection [colds] or simple urinary tract infection) should be monitored to their conclusion or treated, as appropriate, prior to inclusion.
- Active hepatitis-B or hepatitis-C.
- Active tuberculosis.
- Patients with opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, Aspergillosis, histoplasmosis or atypical mycobacterium infection, etc, within the previous six months.
- History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra-clavicular, epitrochlear, or periaortic areas), or splenomegaly.
- Known recent substance abuse (drug or alcohol).
- Poor tolerability of venepuncture or lack of adequate venous access for required blood sampling during the study period.
- Presence of a transplanted organ (with the exception of a corneal transplant > three months prior to screening).
- Patients receiving immunosuppressive therapy within one month of screening.
- Patients with malignancy within the past five years.
- Signs or symptoms of severe, progressive or uncontrolled renal, hepatic, haematologic, gastrointestinal, endocrine, pulmonary, cardiac or neurological disease (including demyelinating diseases such as multiple sclerosis).
- Patients who, within the past three months, have had either a myocardial infarction, uncontrolled congestive cardiac failure, unstable angina, uncontrolled systemic hypotension or uncontrolled systemic hypertension.
- Patients who have screening laboratory values which deviate 20% or more from the upper or lower limits of normal or which are considered to be clinically significant to the investigator.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Centre for Rheumatology and Connective Tissue Diseases, Lower Ground Floor, Royal Free Hospital NHS Trust, Hampstead
London, NW3 2QG
About this study
Official title: A Double-Blind Placebo-Controlled Pilot Study of Safety and Tolerability of AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis
To study the safety and tolerability of a hyperimmune goat serum product (AIMSPRO) in the treatment of systemic sclerosis (SSc) through a period of 26 weeks of study participation. The secondary objective of the study is to assess the efficacy of AIMSPRO as a therapeutic agent for SSc using inter alia the SSc-HAQ questionnaire and the modified Rodnan skin score.
Read the detailed description
Systemic sclerosis (scleroderma, SSc) is a multisystemic disease clinically characterized by fibrosis of the skin, joints, muscles and internal organs. Systemic sclerosis is a rare disease, with an estimated incidence of 19 individuals per million population per year.
The pathogenesis of SSc remains incompletely understood although it seems likely that there is an interplay between inflammatory, vascular and fibroblast dysfunction, leading ultimately to the sustained activation of a population of fibroblasts that deposit increased amounts of extracellular matrix in lesional tissues, including the skin and internal organs.
Impairment of the immune system is currently thought to play an important role. This is based on the observation that in the early phases of SSc, mononuclear cells migrate to the dermis and accumulate around small blood vessels, nerves and skin appendages. Furthermore, there is a direct relation between the extent of cutaneous inflammation and the extent and progression of fibrosis of the skin. Stimulated T-lymphocytes of patients with SSc produce more tumor necrosis factor-α, interleukin-1 and -2 compared with healthy controls and the serum concentrations of IL-2, IL-4, IL-6 and IL-8 and soluble IL-2 receptors are elevated. The occurrence of autoantibodies, predominantly antitopoisomerase-1 (ATA) and anticentromere antibodies (ACA), in approximately 90% of the patients, points to an alteration of the humoral immune system.
Systemic sclerosis can be subdivided into diffuse and limited forms. Diffuse cutaneous SSc (dcSSc) is characterised by skin involvement proximal to the elbows and knees, limited cutaneous SSc (lcSSc) by skin involvement distal to these joints. In approximately 50% of patients with dcSSc, ATA can be detected, and in approximately 50% of patients with lcSSc ACAs are present. Other hallmark autoantibodies have also been identified in smaller proportions of SSc patients including anti-RNA polymerase I/III and anti-fibrillarin antibodies (5).
The course of SSc is variable. In some patients the disease remains confined to sclerodactyly and Raynaud's phenomenon. In other patients there is a relentless progression of internal organ fibrosis, ultimately leading to death. A recent study showed a cumulative 5-year survival rate of 63%. There are efforts to try to identify clinical and investigational predictors of outcome in SSc. One study has identified three clinical variables: raised ESR, proteinuria and impaired lung function indices which are associated with poor outcome. In addition, the various hallmark autoantibodies occurring in SSc are mutually exclusive and several studies in Europe and North America have demonstrated that individuals carrying each of these autoantibodies are associated with different frequencies of internal organ complications. This also allows patients who are at increased risk of pulmonary, cardiac or renal complications to be identified.
At present, no treatment has been definitely shown to be effective in SSc. Because of its presumed immunologic pathogenesis, modulation of the immune system has been the major goal in therapeutic interventions in SSc. Several studies have reported effectiveness of immune modulating drugs in the treatment of this disease, although these have mostly been in open, uncontrolled trials. These drugs include azathioprine, cyclosporin, methotrexate and cyclophosphamide. Amongst these, methotrexate and cyclophosphamide are currently the most widely used. New, more specific immunological treatment modalities have been harnessed in order to improve the treatment and prognosis of scleroderma patients.
In 2005, a patient with systemic sclerosis was treated with AIMSPRO on a compassionate basis with a sustained improvement in mobility and, in particular, there was an improvement in proximal muscle power and skin characteristics.
In this study, twenty patients will receive either AIMSPRO or placebo, 1.0ml subcutaneously, twice weekly for 26 weeks. Standard outcome measures and novel biomarkers will be used to investigate safety, efficacy and response to treatment.
- Conditions
- Systemic Sclerosis
- Being tested
- Hyperimmune caprine serum, Albumin
- Keywords
- Systemic sclerosis, Diffuse cutaneous systemic sclerosis, Scleroderma, Biological, Hyperimmune caprine serum, Goat Serum
- Medical subject headings
- Scleroderma, Systemic, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hyperimmune caprine serumDrug
Also called Ceremben, Hyperimmune goat serum
Subcutaneous injection of serum, 1ml twice weekly for 6 months
AlbuminDrug
Also called Placebo
Subcutaneous injection of albumin, 1ml twice weekly for 6 months
| Study group | Role | What they receive |
|---|---|---|
| AIMSPRO | Experimental | Not described Receives: Drug: Hyperimmune caprine serum |
| Placebo | Placebo comparator | Not described Receives: Drug: Albumin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Modified Rodnan Skin Score
Measured: Baseline, Week 6 and Week 26
Secondary outcomes (5)
Scleroderma Health Assessment Questionnaire
Measured: Baseline, Week 6 and Week 26
Scleroderma UK Functional Score
Measured: Baseline, Week 6 and Week 26
Patient and Physician Global Assessment (VAS)
Measured: Baseline, Week 6 and Week 26
SF-36 (Short form 36)
Measured: Baseline, Week 6 and Week 26
MRC Sum Score
Measured: Week 0, Week 6 and Week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2008 (estimated)
- Study startDec 2008
- Primary completionFeb 2011
- Study completionSep 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Systemic 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daval International Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Christopher P Denton, PhD FRCP, Principal investigator, Royal Free Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00769028
- Sponsor's protocol ID
- DISS01
- Status last verified
- Aug 2011
- First submitted
- 7 Oct 2008
- Last updated
- 18 Aug 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Quillinan N, Clark KE, Youl B, Vernes J, McIntosh D, Haq S, Denton CP. Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis. Arthritis Res Ther. 2017 Mar 7;19(1):45. doi: 10.1186/s13075-017-1252-x.
PubMed 28270187Quillinan NP, McIntosh D, Vernes J, Haq S, Denton CP. Treatment of diffuse systemic sclerosis with hyperimmune caprine serum (AIMSPRO): a phase II double-blind placebo-controlled trial. Ann Rheum Dis. 2014 Jan;73(1):56-61. doi: 10.1136/annrheumdis-2013-203674. Epub 2013 Sep 25.
PubMed 24067785
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Placebo-Controlled Pilot Study of Safety and Tolerability of AIMSPRO in Established Diffuse Cutaneous Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT00769028
- Acronym / sponsor ID
- DISS01
- Conditions
- Systemic Sclerosis
- Keywords
- Systemic sclerosis, Diffuse cutaneous systemic sclerosis, Scleroderma, Biological, Hyperimmune caprine serum, Goat Serum
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Daval International LimitedIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Feb 2011 (actual)
- Study completion
- Sep 2011 (estimated)
- First posted
- 8 Oct 2008 (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.
To study the safety and tolerability of a hyperimmune goat serum product (AIMSPRO) in the treatment of systemic sclerosis (SSc) through a period of 26 weeks of study participation. The secondary objective of the study is to assess the efficacy of AIMSPRO as a therapeutic agent for SSc using inter alia the SSc-HAQ questionnaire and the modified Rodnan skin score.
Detailed description
Systemic sclerosis (scleroderma, SSc) is a multisystemic disease clinically characterized by fibrosis of the skin, joints, muscles and internal organs. Systemic sclerosis is a rare disease, with an estimated incidence of 19 individuals per million population per year.
The pathogenesis of SSc remains incompletely understood although it seems likely that there is an interplay between inflammatory, vascular and fibroblast dysfunction, leading ultimately to the sustained activation of a population of fibroblasts that deposit increased amounts of extracellular matrix in lesional tissues, including the skin and internal organs.
Impairment of the immune system is currently thought to play an important role. This is based on the observation that in the early phases of SSc, mononuclear cells migrate to the dermis and accumulate around small blood vessels, nerves and skin appendages. Furthermore, there is a direct relation between the extent of cutaneous inflammation and the extent and progression of fibrosis of the skin. Stimulated T-lymphocytes of patients with SSc produce more tumor necrosis factor-α, interleukin-1 and -2 compared with healthy controls and the serum concentrations of IL-2, IL-4, IL-6 and IL-8 and soluble IL-2 receptors are elevated. The occurrence of autoantibodies, predominantly antitopoisomerase-1 (ATA) and anticentromere antibodies (ACA), in approximately 90% of the patients, points to an alteration of the humoral immune system.
Systemic sclerosis can be subdivided into diffuse and limited forms. Diffuse cutaneous SSc (dcSSc) is characterised by skin involvement proximal to the elbows and knees, limited cutaneous SSc (lcSSc) by skin involvement distal to these joints. In approximately 50% of patients with dcSSc, ATA can be detected, and in approximately 50% of patients with lcSSc ACAs are present. Other hallmark autoantibodies have also been identified in smaller proportions of SSc patients including anti-RNA polymerase I/III and anti-fibrillarin antibodies (5).
The course of SSc is variable. In some patients the disease remains confined to sclerodactyly and Raynaud's phenomenon. In other patients there is a relentless progression of internal organ fibrosis, ultimately leading to death. A recent study showed a cumulative 5-year survival rate of 63%. There are efforts to try to identify clinical and investigational predictors of outcome in SSc. One study has identified three clinical variables: raised ESR, proteinuria and impaired lung function indices which are associated with poor outcome. In addition, the various hallmark autoantibodies occurring in SSc are mutually exclusive and several studies in Europe and North America have demonstrated that individuals carrying each of these autoantibodies are associated with different frequencies of internal organ complications. This also allows patients who are at increased risk of pulmonary, cardiac or renal complications to be identified.
At present, no treatment has been definitely shown to be effective in SSc. Because of its presumed immunologic pathogenesis, modulation of the immune system has been the major goal in therapeutic interventions in SSc. Several studies have reported effectiveness of immune modulating drugs in the treatment of this disease, although these have mostly been in open, uncontrolled trials. These drugs include azathioprine, cyclosporin, methotrexate and cyclophosphamide. Amongst these, methotrexate and cyclophosphamide are currently the most widely used. New, more specific immunological treatment modalities have been harnessed in order to improve the treatment and prognosis of scleroderma patients.
In 2005, a patient with systemic sclerosis was treated with AIMSPRO on a compassionate basis with a sustained improvement in mobility and, in particular, there was an improvement in proximal muscle power and skin characteristics.
In this study, twenty patients will receive either AIMSPRO or placebo, 1.0ml subcutaneously, twice weekly for 26 weeks. Standard outcome measures and novel biomarkers will be used to investigate safety, efficacy and response to treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AIMSPRO | Experimental | Drug: Hyperimmune caprine serum |
| Placebo | Placebo comparator | Drug: Albumin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Must fulfill 1980 Preliminary Classification Criteria for systemic sclerosis of the American Rheumatism Association
- Diffuse cutaneous SSc, as evidenced by skin sclerosis proximal to the elbows or knees and absence of the anti-centromere autoantibody
- At least three years must have elapsed since the first non-Raynaud's manifestation
- Men and women of childbearing potential must use adequate birth control measures for the duration of the study and should continue such precautions for six months after receiving the last injection of AIMSPRO.
- Screening laboratory test results:
Key exclusion criteria (19 listed)
- Women who are pregnant, nursing, or planning pregnancy within one and a half years after screening (i.e., approximately six months following last injection of study drug).
- Use of any investigational drug within one month prior to screening or within five half-lives of the investigational agent, whichever is longer.
- Use of a putative disease modifying drug (potential immunosuppressive drug) within one month of screening.
- Treatment with any therapeutic agent targeted at reducing TNF (e.g., infliximab, pentoxifylline, thalidomide, etanercept, etc.) within three months of screening.
- Previous administration of AIMSPRO.
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 |
|---|---|---|
| Hyperimmune caprine serumAlso: Ceremben, Hyperimmune goat serumSubcutaneous injection of serum, 1ml twice weekly for 6 months | Drug | AIMSPRO |
| AlbuminAlso: PlaceboSubcutaneous injection of albumin, 1ml twice weekly for 6 months | Drug | Placebo |
Primary outcome
Modified Rodnan Skin Score
Time frame: Baseline, Week 6 and Week 26
5 secondary outcomes
Scleroderma Health Assessment Questionnaire
Time frame: Baseline, Week 6 and Week 26
Scleroderma UK Functional Score
Time frame: Baseline, Week 6 and Week 26
Patient and Physician Global Assessment (VAS)
Time frame: Baseline, Week 6 and Week 26
SF-36 (Short form 36)
Time frame: Baseline, Week 6 and Week 26
MRC Sum Score
Time frame: Week 0, Week 6 and Week 26
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2011.
- Derived from this study: PubMed 28270187Quillinan N, Clark KE, Youl B, Vernes J, McIntosh D, Haq S, Denton CP. Multiplex serum protein analysis reveals potential mechanisms and markers of response to hyperimmune caprine serum in systemic sclerosis. Arthritis Res Ther. 2017 Mar 7;19(1):45. doi: 10.1186/s13075-017-1252-x.
- Derived from this study: PubMed 24067785Quillinan NP, McIntosh D, Vernes J, Haq S, Denton CP. Treatment of diffuse systemic sclerosis with hyperimmune caprine serum (AIMSPRO): a phase II double-blind placebo-controlled trial. Ann Rheum Dis. 2014 Jan;73(1):56-61. doi: 10.1136/annrheumdis-2013-203674. Epub 2013 Sep 25.
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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.
Christopher P Denton, PhD FRCP principal investigator
Royal Free Hospital NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hyperimmune caprine serum and Albumin in people with Systemic Sclerosis, run by Daval International Limited 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 9 inclusion and 19 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: status not confirmed, as of the sponsor's last update on 18 Aug 2011. 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 phase mean?
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?
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?
Modified Rodnan Skin Score (time frame: Baseline, Week 6 and Week 26). 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 NCT00769028, which also lists 2 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 18 Aug 2011.