Colitis, UlcerativePhase 1NCT01984047
Single Dose Escalation Trial to Evaluate the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of GSK3050002
A Phase 1 study testing GSK3050002 in people with Colitis, Ulcerative, run by GlaxoSmithKline at 1 site in United Kingdom.
Trial summary
The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- GSK3050002
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 49 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Jan 2014to 23 Feb 2015
- 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 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12- lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria may be included only if the Investigator in consultation with the GSK Medical Monitor [if required] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body mass index (BMI) within the range 18 - 29 kilogram per meter square [kg/m^2] (inclusive).
- Male subjects with female partners of child-bearing potential must agree to use one of the listed contraception methods. This criterion must be followed for 1 month prior to the first dose of study medication for 15 weeks post dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Suitable for cannulation and with adequate venous access.
- Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin <= 1.5xUpper limit of Normal [ULN] (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Based on a single ECG QTcF < 450 milliseconds (msec).
Who cannot join
- Criteria Based Upon Medical Histories
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- History of severe drug allergies including type 1 hypersensitivity reaction to parental administration of contrast agents, human or murine proteins or monoclonal antibodies.
- Subject has acne which requires prescription treatment
Show all 19Show fewer
- Criteria Based Upon Diagnostic Assessments
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- A positive pre-study drug/alcohol screen.
- A positive test for Human immunodeficiency virus (HIV) antibody.
- Subject is a heavy smoker as defined by a positive smoking breath test of >10 parts per million (ppm) carbon monoxide (CO).
- Other Criteria
- Evidence of current or at risk of developing bacterial, fungal, or viral infection at screening or within 7 days before dosing.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Subject is unable to refrain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements), within 7 days prior to the first dose of study medication until completion of the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study.
- Subject is unable to abstain from travelling to area which carry a high risk of infection for the duration of the study.
- Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- Subject is unable to abstain from being vaccinated or immunized for 4 weeks prior to dosing and for 19 weeks after the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Randomized, Double-Blind (Sponsor Open), Placebo-Controlled, Single Dose Escalation Trial to Evaluate the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of GSK3050002 (Anti-CCL20 Monoclonal Antibody) in Healthy Male Volunteers
The primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Subjects will be admitted to the clinical unit the evening prior to dosing when each subject will receive a single intravenous dose of GSK3050002 or placebo, then remain in house under supervision until discharged on Day 3. Subjects will then return for 7 outpatient visits scheduled over the following 81 days. Finally, the follow-up visit will be 7-14 days following the last visit.
- Conditions
- Colitis, Ulcerative
- Being tested
- GSK3050002, Placebo
- Keywords
- safety, GSK3050002, CCR6 receptor, single dose escalation, Phase 1, CCL20
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3050002Drug
GSK3050002 is a white to off-white lyophilized powder that will be reconstituted with sterile water for intravenous infusion. It is available in the concentrations of 0.1 milligram (mg)/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg.
PlaceboDrug
Placebo contains normal saline (0.9% sodium chloride) for intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| GSK3050002 0.1 mg | Experimental | Six subjects in this cohort will receive a single dose of GSK3050002 0.1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects (i.e. 1 subject will be dosed with GSK3050002 and 1 with placebo before the remainder of the cohort is dosed) will be used in the cohort. Receives: Drug: GSK3050002; Drug: Placebo |
| GSK3050002 0.5 mg | Experimental | Six subjects in this cohort will receive a single dose of GSK3050002 0.5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. Receives: Drug: GSK3050002; Drug: Placebo |
| GSK3050002 1 mg | Experimental | Six subjects in this cohort will receive a single dose of GSK3050002 1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort Receives: Drug: GSK3050002; Drug: Placebo |
| GSK3050002 5 mg | Experimental | Six subjects in this cohort will receive a single dose of GSK3050002 5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. Receives: Drug: GSK3050002; Drug: Placebo |
| GSK3050002 10 mg | Experimental | Six subjects in this cohort will receive a single dose of GSK3050002 10 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. Receives: Drug: GSK3050002; Drug: Placebo |
| GSK3050002 20 mg | Experimental | Six subjects in this cohort will receive a single dose of GSK3050002 20 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. Receives: Drug: GSK3050002; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events
Adverse events will be collected from the start of study treatment until the follow-up contact
Measured: Up to Day 98
Laboratory measurements
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests
Measured: Up to Day 98
Electrocardiogram (ECG) assessment as a measure of safety
Triplicate 12-lead ECG will be recorded before dosing on Day 1 (Pre-dose) and a single 12-lead ECG will be obtained at all other timepoints
Measured: Up to Day 98
Vital signs as a measure of safety
Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate
Measured: Up to Day 98
Pharmacokinetic (PK) parameters after a single intravenous dose of GSK3050002
The following PK parameters will be determined: maximum observed serum concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC[0-t] and AUC[0-infinity]), and apparent terminal phase half-life (t1/2)
Measured: Day 1, Day 2, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84
Secondary outcomes (2)
Chemokine (C-C motif) ligand 20 (CCL20) levels in blood
Whole blood may be collected for in vitro stimulation and measurement of CCL20 activity in a biological assay. Analysis of serum levels of total (free and drug bound) CCL20 may be performed
Measured: Up to Day 87
Immunogenicity development as assessed from anti-drug antibody
An assay for detecting anti-drug antibodies (ADA) against GSK305002 will be developed and validated using an electrochemiluminescent (ECL) bridging assay. Testing will be performed using the typical tiered approach involving screening, confirmation, and titration assays. If sera contain potential anti- GSK3050002 antibodies, they will be confirmed by immunocompetition using excess drug. Confirmed samples with such antibodies will be further analyzed for titers and may be characterized for neutralizing activity by a neutralization assay
Measured: Up to Day 87
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2013 (estimated)
- Study start10 Jan 2014
- Primary completion23 Feb 2015
- Study completion23 Feb 2015
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 Colitis, UlcerativeStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01984047
- Sponsor's protocol ID
- 200784
- Status last verified
- Jul 2018
- First submitted
- 7 Nov 2013
- Last updated
- 24 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Laffan SB, Thomson AS, Mai S, Fishman C, Kambara T, Nistala K, Raymond JT, Chen S, Ramani T, Pageon L, Polsky R, Watkins M, Ottolangui G, White JR, Maier C, Herdman M, Bouma G. Immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against CCL20 is associated with complement-containing drug aggregates. PLoS One. 2020 Apr 23;15(4):e0231655. doi: 10.1371/journal.pone.0231655. eCollection 2020.
PubMed 32325480
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Randomized, Double-Blind (Sponsor Open), Placebo-Controlled, Single Dose Escalation Trial to Evaluate the Safety, Tolerability Pharmacokinetics and Pharmacodynamics of GSK3050002 (Anti-CCL20 Monoclonal Antibody) in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT01984047
- Acronym / sponsor ID
- 200784
- Conditions
- Colitis, Ulcerative
- Keywords
- safety, GSK3050002, CCR6 receptor, single dose escalation, Phase 1, CCL20
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Collaborators
- Eisai Inc.
- Study start
- 10 Jan 2014 (actual)
- Primary completion
- 23 Feb 2015 (actual)
- Study completion
- 23 Feb 2015 (actual)
- First posted
- 14 Nov 2013 (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 primary purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of GSK3050002 in humans. Subjects will attend the clinical unit for a screening visit and if eligible and consenting, will attend to participate in the study within 30 days. Subjects will be admitted to the clinical unit the evening prior to dosing when each subject will receive a single intravenous dose of GSK3050002 or placebo, then remain in house under supervision until discharged on Day 3. Subjects will then return for 7 outpatient visits scheduled over the following 81 days. Finally, the follow-up visit will be 7-14 days following the last visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| GSK3050002 0.1 mg | Experimental | Drug: GSK3050002, Drug: PlaceboSix subjects in this cohort will receive a single dose of GSK3050002 0.1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects (i.e. 1 subject will be dosed with GSK3050002 and 1 with placebo before the remainder of the cohort is dosed) will be used in the cohort. |
| GSK3050002 0.5 mg | Experimental | Drug: GSK3050002, Drug: PlaceboSix subjects in this cohort will receive a single dose of GSK3050002 0.5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. |
| GSK3050002 1 mg | Experimental | Drug: GSK3050002, Drug: PlaceboSix subjects in this cohort will receive a single dose of GSK3050002 1 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort |
| GSK3050002 5 mg | Experimental | Drug: GSK3050002, Drug: PlaceboSix subjects in this cohort will receive a single dose of GSK3050002 5 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. |
| GSK3050002 10 mg | Experimental | Drug: GSK3050002, Drug: PlaceboSix subjects in this cohort will receive a single dose of GSK3050002 10 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. |
| GSK3050002 20 mg | Experimental | Drug: GSK3050002, Drug: PlaceboSix subjects in this cohort will receive a single dose of GSK3050002 20 mg and two subjects will receive a single dose of placebo intravenously. Sentinel subjects will be used in the cohort. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male aged between 18 and 65 years of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and 12- lead ECG. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria may be included only if the Investigator in consultation with the GSK Medical Monitor [if required] agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Body mass index (BMI) within the range 18 - 29 kilogram per meter square [kg/m^2] (inclusive).
- Male subjects with female partners of child-bearing potential must agree to use one of the listed contraception methods. This criterion must be followed for 1 month prior to the first dose of study medication for 15 weeks post dose.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Key exclusion criteria (19 listed)
- Criteria Based Upon Medical Histories
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >21 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- History of severe drug allergies including type 1 hypersensitivity reaction to parental administration of contrast agents, human or murine proteins or monoclonal antibodies.
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 |
|---|---|---|
| GSK3050002GSK3050002 is a white to off-white lyophilized powder that will be reconstituted with sterile water for intravenous infusion. It is available in the concentrations of 0.1 milligram (mg)/kg, 0.5 mg/kg, 1 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg. | Drug | GSK3050002 0.1 mg, GSK3050002 0.5 mg, GSK3050002 1 mg, GSK3050002 10 mg, GSK3050002 20 mg, GSK3050002 5 mg |
| PlaceboPlacebo contains normal saline (0.9% sodium chloride) for intravenous infusion | Drug | GSK3050002 0.1 mg, GSK3050002 0.5 mg, GSK3050002 1 mg, GSK3050002 10 mg, GSK3050002 20 mg, GSK3050002 5 mg |
Primary outcome
Number of subjects with adverse events
Time frame: Up to Day 98
Adverse events will be collected from the start of study treatment until the follow-up contact
Laboratory measurements
Time frame: Up to Day 98
Clinical laboratory assessments will include haematology, clinical chemistry, urinalysis and other screening tests
Electrocardiogram (ECG) assessment as a measure of safety
Time frame: Up to Day 98
Triplicate 12-lead ECG will be recorded before dosing on Day 1 (Pre-dose) and a single 12-lead ECG will be obtained at all other timepoints
Vital signs as a measure of safety
Time frame: Up to Day 98
Vital sign measurements will include systolic and diastolic blood pressure, temperature, and pulse rate
Pharmacokinetic (PK) parameters after a single intravenous dose of GSK3050002
Time frame: Day 1, Day 2, Day 3, Day 7, Day 14, Day 21, Day 28, Day 42, Day 56 and Day 84
The following PK parameters will be determined: maximum observed serum concentration (Cmax), time to Cmax (tmax), area under the serum concentration-time curve (AUC[0-t] and AUC[0-infinity]), and apparent terminal phase half-life (t1/2)
2 secondary outcomes
Chemokine (C-C motif) ligand 20 (CCL20) levels in blood
Time frame: Up to Day 87
Immunogenicity development as assessed from anti-drug antibody
Time frame: Up to Day 87
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 24 Jul 2018.
- Derived from this study: PubMed 32325480Laffan SB, Thomson AS, Mai S, Fishman C, Kambara T, Nistala K, Raymond JT, Chen S, Ramani T, Pageon L, Polsky R, Watkins M, Ottolangui G, White JR, Maier C, Herdman M, Bouma G. Immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against CCL20 is associated with complement-containing drug aggregates. PLoS One. 2020 Apr 23;15(4):e0231655. doi: 10.1371/journal.pone.0231655. eCollection 2020.
- Results for study 200784 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
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 GSK3050002 in people with Colitis, Ulcerative, run by GlaxoSmithKline 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 8 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: finished, as of the sponsor's last update on 24 Jul 2018. 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. 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?
Number of subjects with adverse events (time frame: Up to Day 98). The study lists 5 primary outcomes in all. 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 NCT01984047, 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 24 Jul 2018.