Crohn DiseasePhase 1/2CDAIDNCT03681067
A Clinical Trial of Antibody GSK1070806 in the Treatment of Patients With Moderate to Severe Crohn's Disease
A Phase 1/2 study testing GSK1070806 in people with Crohn Disease, run by University of Birmingham at 1 site in United Kingdom.
Trial summary
This trial aims to investigate the safety, tolerability and clinical activity of humanised antibody GSK1070806 delivered via intravenous infusion in the treatment of patients with moderate-to-severe Crohn's disease. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Crohn Disease
- What is being tested?
- GSK1070806
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 20 Feb 2019to 2 Jun 2020
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- A patient will be eligible for inclusion in this study only if all of the following criteria apply:
- Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications. (see Section 7.11 for additional information)
- Patients that have been diagnosed with moderate to severe Crohn's disease for at least 3 months prior to Screening Visit 1
- Patients are required to have endoscopic evidence of active Crohn's disease at Baseline defined by endoscopic appearance: SES-CD excluding the narrowed component of ≥ 6 (or ≥4 for patients with isolated ileal disease).
- AST and ALT ≤ 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
- Male or female participants aged ≥16 years (up to 80 years)
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- Male participants:
- A male participant must agree to use contraception as detailed in Appendix 5 of this protocol for at least 180 days post-dose of study medication and refrain from donating sperm during this period.
- Female participants:
- If the patient is breastfeeding, she must agree to stop breastfeeding once randomised into the trial.*
- A patient is eligible to participate if she is not pregnant.
- A woman of childbearing potential (WOCBP) is eligible only if she meets at least one of the following conditions:
- Females on HRT and whose menopausal status is in doubt will be required to use one of the non-hormonal highly effective contraception methods if they wish to continue their HRT during the trial. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before trial enrolment.
- Agrees to follow the contraceptive guidance in Appendix 5 for at least 180 days post-dose of trial medication. If a hormonal method of birth control is selected from the list in Appendix 5 then patients must have been using these methods at least 1 month prior to GSK1070806 administration, or be abstinent, or utilise a condom as a method of contraception until the selected hormonal method has been in place for the 28 day period.
- A woman who is not of childbearing potential is eligible only if she meets at least one of the following conditions:
- Premenopausal female with documented hysterectomy ii Premenopausal female with documented bilateral salpingectomy or oophorectomy iii. Postmenopausal female defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement
- A female patient who is breastfeeding may be screened. If randomised into the trial, this patient must agree to stop breastfeeding. Patients who are screened but ineligible can continue breastfeeding.
- therapy (HRT). However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.
Who cannot join
- A participant will not be eligible for inclusion in this trial if any of the following criteria apply:
- Diagnosis of ulcerative or indeterminate colitis
- Crohn's Disease complications:
- Evidence of an infected abscess by MRI or other examinations
- Bowel surgery other than appendectomy within 12 weeks prior to screen and/or has planned surgery or deemed likely to need surgery for CD during the trial period
- Participants with ileostomies, colostomies or rectal pouches
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- Participants with a bowel stricture that is fixed
- Participants with evidence of short bowel syndrome
- Participants requiring enteral or parenteral feeding
- Deep penetrating ulcers at endoscopy thought to be at risk for perforation
- Viral and bacterial infections:
- Presence of Hepatitis B surface antigen (HBsAg), (confirmed by Hepatitis B surface antigen test - within 12 months of randomisation) core antigen (HBcAg) or surface antibody (HBsAb), positive Hepatitis C (qualitative enzyme immunoassay) test result
- Known varicella, herpes zoster, or other severe viral infection within 6 weeks of randomisation
- The participant has a history of tuberculosis (TB) disease or latent TB infection, in the absence of documented adequate therapy for same.
- Positive screening test for TB (including T-SPOT.TB TB test), unless respiratory review confirms false positive test results
- History of uncontrolled bacterial or fungal infection requiring intravenous antibiotics
- Positive immunoassay for Clostridium difficile toxin and other enteric pathogens
- Other exclusion criteria:
- Cardiology assessment/co-morbidity defined as:
- QTc >450 msec (480msec for those with Bundle Branch Block) and/or ii. either QTcb or QTcf, machine or manual overread, males or females. The QT correction formula used to determine exclusion and discontinuation should be the same throughout the trial and/or iii. based on single QTc value (average of triplicate readings) of ECG obtained over a brief recording period
- The participant has congenital or acquired immunodeficiency, or a history of chronic or recurrent opportunistic infections
- The participant has current evidence of, or has been treated for a malignancy within the past five years (other than localised basal cell, squamous cell skin cancer, cervical dysplasia, or cancer in situ that has been resected)
- Use of any investigational drug within 30 days prior to screening, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
- Participant has received live, attenuated or recombinant vaccine(s) within 2 months of randomisation or will require vaccination within 3 months of trial drug infusion
- Any patients that are receiving medication(s) detailed in Section 7.11.2 of the trial protocol, will not be eligible for randomisation into the trial
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University Hospitals Birmingham NHS Foundation Trust
Birmingham, B15 2TH
About this study
Official title: A Phase Ib/IIb, Randomised, Double Blind, Placebo-Controlled Trial to Investigate the Safety, Tolerability and Clinical Activity of Humanised Antibody GSK1070806 in the Treatment of Patients With Moderate-to-Severe Crohn's Disease
This trial aims to investigate the safety, tolerability and clinical activity of humanised antibody GSK1070806 delivered via intravenous infusion in the treatment of patients with moderate-to-severe Crohn's disease. 30-36 patients will be enrolled into the trial, with two thirds of the patients receiving active drug and one third receiving placebo. After 30 patients have been recruited into the study the sample size will be reassessed and up to an additional 6 patients could be recruited (i.e. up to 36 patients).
Read the detailed description
The proposed study will be a randomised, double blind, placebo-controlled trial to investigate the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of single intravenous infusion (one dose on Day 1) of GSK1070806 or placebo, in patients with active, moderate to severe CD. The primary objective of the study is to assess the safety and tolerability of a single dose IV administration of GSK1070806. A secondary objective will be to evaluate the effect of GSK1070806 in change of CDAI over time. Further secondary endpoints will include assessment of endoscopic response in patients at week 12. (Other secondary endpoints are detailed in Section 2.3).
30 patients will be recruited with randomisation of 2:1 active drug to placebo in multiple centres in the UK. After 30 patients have been recruited into the study the sample size will be reassessed and up to an additional 6 patients could be recruited (i.e. up to 36 patients). These additional patients will also be recruited with randomisation of 2:1 active drug to placebo.
An initial screening shall take place to identify patients diagnosed with CD for at least 3 months prior to screening, active disease based on CDAI score of 220-450 points and colonoscopic confirmation of active mucosal inflammation (SES-CD excluding narrowed component ≥6; or in patients with isolated ileal disease ≥4).
Patients who do not have colonoscopically demonstrated mucosal inflammation will be excluded even if they have MRI evidence of Crohn's disease more proximally in the small intestine. For inclusion, CDAI criteria have to be fulfilled within 7 days prior to dosing and colonoscopic SES-CD criteria has to be fulfilled with 28 days prior to dosing.
The induction of clinical activity will be assessed at week 12 by CDAI score, average clinical SF and/or AP scores as well as by colonoscopic assessment of baseline video images and week 12 video images.
The first 5 patients randomised into the trial will be dosed at least 3 days apart. At the interim analysis time point, a safety decision will be taken on the subsequent recruitment and patient spacing out strategy.
- Conditions
- Crohn Disease
- Being tested
- GSK1070806, Placebo- sodium chloride
- Keywords
- Crohn's disease, CDAID, CDAI, GSK1070806
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK1070806Drug
GSK1070806 100mg/ml injectable solution will be delivered via intravenous infusion as a single infusion
Placebo- sodium chlorideDrug
Also called Placebo
Placebo injectable solution will be delivered via intravenous infusion as a single infusion
| Study group | Role | What they receive |
|---|---|---|
| GSK10708060 | Experimental | Humanised antibody GSK1070806 Receives: Drug: GSK1070806 |
| Placebo - sodium chloride | Placebo comparator | Placebo Receives: Drug: Placebo- sodium chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability parameters include: adverse events and serious adverse events
NCI-CTCAE criterion Version 4
Measured: 24 weeks
Safety and tolerability parameters include: clinical laboratory tests (Haematology)
Haematology panel : haemoglobin (g/L), Platelets (10*9/L), White Blood Cells (10*9/L), International normalized ratio, Neutrophils (10*9/L)
Measured: 24 weeks
Safety and tolerability parameters include: clinical laboratory tests (Biochemistry)
Biochemistry Panel : Creatinine (umol/L), Sodium (mmol/L), Potassium (mmol/l), Bilirubin (umol/L), Alanine Transferase (u/L) Aspartate Transaminase (U/L), Albumin (g/L), eGFR ml/min/1.7, C-Reactive Protein (CRP)
Measured: 24 weeks
Safety and tolerability parameters include: Cardiology
Electrocardiogram review - for any abnormalities i.e. QT interval etc.
Measured: 24 weeks
Safety and tolerability parameters include: frequency, type and severity of infections
NCI-CTCAE criterion Version 4 - grading system used
Measured: 24 weeks
Safety and tolerability parameters include: Heart Rate (vital signs)
Heart rate
Measured: 24 weeks
Safety and tolerability parameters include: Blood Pressure (vital signs)
Blood pressure
Measured: 24 weeks
Safety and tolerability parameters include: Body Temperature (vital signs)
Oral body temperature
Measured: 24 weeks
Safety and tolerability parameters include: Respiratory Rate (vital signs)
Respiratory rate
Measured: 24 weeks
Secondary outcomes (1)
CDAI score over time. Patients
Crohns disease activity index score (Pre-treatment, Post treatment). Scale ranges from <150(remission) to >450(severe Crohn's disease).
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2018
- Study start20 Feb 2019
- Primary completion2 Jun 2020
- Study completion2 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, University Hospital Birmingham
- Responsible party
- Sponsor
- Investigators
- Marietta Iacucci, MD,PhD, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03681067
- Sponsor's protocol ID
- RG_17-258
- Other IDs
- 2018-002001-65, 2018
- Acronym
- CDAID
- Status last verified
- Apr 2021
- First submitted
- 20 Aug 2018
- Last updated
- 28 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/IIb, Randomised, Double Blind, Placebo-Controlled Trial to Investigate the Safety, Tolerability and Clinical Activity of Humanised Antibody GSK1070806 in the Treatment of Patients With Moderate-to-Severe Crohn's Disease
- ClinicalTrials.gov ID
- NCT03681067
- Acronym / sponsor ID
- CDAID / RG_17-258
- Conditions
- Crohn Disease
- Keywords
- Crohn's disease, CDAID, CDAI, GSK1070806
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, University Hospital Birmingham
- Study start
- 20 Feb 2019 (actual)
- Primary completion
- 2 Jun 2020 (actual)
- Study completion
- 2 Jun 2020 (actual)
- First posted
- 21 Sep 2018 (actual)
- 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.
This trial aims to investigate the safety, tolerability and clinical activity of humanised antibody GSK1070806 delivered via intravenous infusion in the treatment of patients with moderate-to-severe Crohn's disease. 30-36 patients will be enrolled into the trial, with two thirds of the patients receiving active drug and one third receiving placebo. After 30 patients have been recruited into the study the sample size will be reassessed and up to an additional 6 patients could be recruited (i.e. up to 36 patients).
Detailed description
The proposed study will be a randomised, double blind, placebo-controlled trial to investigate the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of single intravenous infusion (one dose on Day 1) of GSK1070806 or placebo, in patients with active, moderate to severe CD. The primary objective of the study is to assess the safety and tolerability of a single dose IV administration of GSK1070806. A secondary objective will be to evaluate the effect of GSK1070806 in change of CDAI over time. Further secondary endpoints will include assessment of endoscopic response in patients at week 12. (Other secondary endpoints are detailed in Section 2.3).
30 patients will be recruited with randomisation of 2:1 active drug to placebo in multiple centres in the UK. After 30 patients have been recruited into the study the sample size will be reassessed and up to an additional 6 patients could be recruited (i.e. up to 36 patients). These additional patients will also be recruited with randomisation of 2:1 active drug to placebo.
An initial screening shall take place to identify patients diagnosed with CD for at least 3 months prior to screening, active disease based on CDAI score of 220-450 points and colonoscopic confirmation of active mucosal inflammation (SES-CD excluding narrowed component ≥6; or in patients with isolated ileal disease ≥4).
Patients who do not have colonoscopically demonstrated mucosal inflammation will be excluded even if they have MRI evidence of Crohn's disease more proximally in the small intestine. For inclusion, CDAI criteria have to be fulfilled within 7 days prior to dosing and colonoscopic SES-CD criteria has to be fulfilled with 28 days prior to dosing.
The induction of clinical activity will be assessed at week 12 by CDAI score, average clinical SF and/or AP scores as well as by colonoscopic assessment of baseline video images and week 12 video images.
The first 5 patients randomised into the trial will be dosed at least 3 days apart. At the interim analysis time point, a safety decision will be taken on the subsequent recruitment and patient spacing out strategy.
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 |
|---|---|---|
| GSK10708060 | Experimental | Drug: GSK1070806Humanised antibody GSK1070806 |
| Placebo - sodium chloride | Placebo comparator | Drug: Placebo- sodium chloridePlacebo |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (18 listed)
- A patient will be eligible for inclusion in this study only if all of the following criteria apply:
- Written informed consent prior to any of the screening procedures including discontinuation of prohibited medications. (see Section 7.11 for additional information)
- Patients that have been diagnosed with moderate to severe Crohn's disease for at least 3 months prior to Screening Visit 1
- Patients are required to have endoscopic evidence of active Crohn's disease at Baseline defined by endoscopic appearance: SES-CD excluding the narrowed component of ≥ 6 (or ≥4 for patients with isolated ileal disease).
- AST and ALT ≤ 2xULN; alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
Key exclusion criteria (25 listed)
- A participant will not be eligible for inclusion in this trial if any of the following criteria apply:
- Diagnosis of ulcerative or indeterminate colitis
- Evidence of an infected abscess by MRI or other examinations
- Bowel surgery other than appendectomy within 12 weeks prior to screen and/or has planned surgery or deemed likely to need surgery for CD during the trial period
- Participants with ileostomies, colostomies or rectal pouches
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 |
|---|---|---|
| GSK1070806GSK1070806 100mg/ml injectable solution will be delivered via intravenous infusion as a single infusion | Drug | GSK10708060 |
| Placebo- sodium chlorideAlso: PlaceboPlacebo injectable solution will be delivered via intravenous infusion as a single infusion | Drug | Placebo - sodium chloride |
Primary outcome
Safety and tolerability parameters include: adverse events and serious adverse events
Time frame: 24 weeks
NCI-CTCAE criterion Version 4
Safety and tolerability parameters include: clinical laboratory tests (Haematology)
Time frame: 24 weeks
Haematology panel : haemoglobin (g/L), Platelets (10*9/L), White Blood Cells (10*9/L), International normalized ratio, Neutrophils (10*9/L)
Safety and tolerability parameters include: clinical laboratory tests (Biochemistry)
Time frame: 24 weeks
Biochemistry Panel : Creatinine (umol/L), Sodium (mmol/L), Potassium (mmol/l), Bilirubin (umol/L), Alanine Transferase (u/L) Aspartate Transaminase (U/L), Albumin (g/L), eGFR ml/min/1.7, C-Reactive Protein (CRP)
Safety and tolerability parameters include: Cardiology
Time frame: 24 weeks
Electrocardiogram review - for any abnormalities i.e. QT interval etc.
Safety and tolerability parameters include: frequency, type and severity of infections
Time frame: 24 weeks
NCI-CTCAE criterion Version 4 - grading system used
Safety and tolerability parameters include: Heart Rate (vital signs)
Time frame: 24 weeks
Heart rate
Safety and tolerability parameters include: Blood Pressure (vital signs)
Time frame: 24 weeks
Blood pressure
Safety and tolerability parameters include: Body Temperature (vital signs)
Time frame: 24 weeks
Oral body temperature
Safety and tolerability parameters include: Respiratory Rate (vital signs)
Time frame: 24 weeks
Respiratory rate
1 secondary outcome
CDAI score over time. Patients
Time frame: 28 weeks
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 28 Apr 2021.
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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.
Marietta Iacucci, MD,PhD principal investigator
University of Birmingham
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 GSK1070806 in people with Crohn Disease, run by University of Birmingham 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 18 inclusion and 25 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 28 Apr 2021. 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 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 and tolerability parameters include: adverse events and serious adverse events (time frame: 24 weeks). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2021.