Graves DiseasePhase 1NCT02973802

ATX-GD-59 in Patients With Graves Disease Not Treated With Anti-thyroid Therapy

A Phase 1 study testing ATX-GD-59 in people with Graves Disease, run by Apitope International NV at 8 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Graves Disease
What is being tested?: ATX-GD-59
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 12 participants
Where: 8 sitesUnited Kingdom
Study dates: Sep 2016to 14 Feb 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

A diagnosis of Graves' disease as assessed by a physician from clinical and laboratory findings and not receiving anti-thyroid therapy.
Quantifiable levels of TSHR antibodies.
Raised levels of free T3 and/or free T4 (not exceeding 15 pmol/L and 35 pmol/L respectively) including undetectable levels of thyroid stimulating hormone.
HLA-DRB1*15, HLA DRB1*03 and or HLA DRB1*04 positive.
Age 18 - 65 years inclusive at the time of informed consent.
The subject must be willing and able to give written informed consent and must be willing to comply with protocol assessments/procedures.
Male subjects must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control for the duration of the study until at least 90 days after the last dose of ATX-GD-59.
Female subjects of child bearing potential must: - neither be pregnant nor breast-feeding, nor attempting to conceive, and - use a highly effective method of contraception as defined below, throughout the entire duration of the study and for at least 90 days after the last dose of ATX-GD-59. A serum pregnancy test will be performed at the screening visit in women of child bearing potential. Thereafter urine pregnancy tests will be performed. A positive result will exclude the woman from the study immediately. A highly effective method of contraception is defined as those which result in a low failure rate when used consistently and correctly such as implants, injectable, combined oral contraceptives, some Intrauterine Devices (IUDs), unless post-menopausal or surgically sterilized. Barrier forms of contraception are considered appropriate when used in combination with one of the above methods.

Who cannot join

Subjects who are pregnant or breastfeeding and/or subjects in the post-partum period.
A known history of, or hypersensitivity reactions that in the opinion of the investigator would exclude the subjects' participation in the study.
Treatment with any Anti-Thyroid Drugs eg carbimazole within the previous 3 months prior to Study Day 1.
Previous treatment with radioiodine or (partial or complete) thyroidectomy.
Signs of moderate or severe orbitopathy including optic nerve compression requiring steroids and/or a clinical activity score >3.
Large and compressive goitres causing localised symptoms such as difficulty swallowing or breathing.

Show all 19Show fewer

Treatment with steroids (administered via the oral and/or parenteral routes) or adrenocorticotropic hormone with the exception of inhaled steroids within the three months prior to Study Day 1.
Symptoms and signs of thyroid storm such as confusion, pyrexia with no other cause than hyperthyroidism.
Significant cardiac disease and/or atrial fibrillation that would require urgent treatment of thyrotoxicosis.
Prior treatment with biological or peptide-based therapeutics including rituximab.
Prior use of disease related T cell vaccine or peptide-tolerising agent to treat Graves' disease.
Detectable levels of antibodies in plasma specific for any of the peptides within ATX-GD-59 at the screening visit.
A history of significant drug allergies.
The use of any investigational drug, or participation in any Clinical Trial within three months prior to Study Day 1.
Treatment with any cytokine or anti-cytokine therapy within three months prior to Study Day 1.
Inadequate liver function, defined by a total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 3 times the upper limit of the normal values at Screening visit. 17. Subject with any significant medical illness or psychiatric condition that in the opinion of the Investigator, would preclude participation in the study or impair the ability to give informed consent; any other clinically apparent autoimmune disease.
18. Clinically significant illness, as determined by the investigator, within 4 weeks prior to the first dose (Study Day 1) of ATX-GD-59.
19. Known history of active or chronic infectious disease or any disease which compromises immune function (e.g. HIV+, HTLV-1, Lyme disease, Latent or active TB, Hepatitis).
20. Major surgery in previous four weeks before screening visit. 21. Known osteoporosis or metabolic bone disease.

Trial locations and contacts

8 sites in 1 country.

City, postcode or hospital

8 sites in 1 country

United Kingdom8 sites

Queen Elizabeth Hospital
Birmingham
University Hospital of Wales
Cardiff
Royal Devon and Exeter Hospital
Exeter
St James's University Hospital
Leeds, LS9 7TF
Hammersmith Hospital
London, W12 0HS
Kings College Hospital
London
The Christie
Manchester
Royal Victoria Infirmary
Newcastle

Other trials in United Kingdom

About this study

Official title: Safety and Proof of Principle Study of ATX-GD-59 in Male and Female Subjects With Graves' Disease Not Currently Treated With Anti-thyroid Therapy: An Open Label Study, With an Upward Titration Over Five Dose Levels Administered by Intradermal Injection

Phase 1 study to assess the safety and biological activity of ATX-GD-59 in patients with Graves Disease not currently treated with anti-thyroid therapy. This will be an open label dose titration involving injections on 10 occasions, each two weeks apart. After dosing is complete there will be a 12 week follow up period. Blood samples will be drawn throughout the study to monitor safety and the body's response to the injections. Thyroid function will be measured throughout the trial to monitor Graves disease progression.

Conditions: Graves Disease
Being tested: ATX-GD-59
Keywords: Graves Disease, Phase 1
Medical subject headings: Graves Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ATX-GD-59Biological
Disease specific immune modulating treatment for Graves Disease

Study groups in NCT02973802
Study group	Role	What they receive
ATX-GD-59 treatment	Experimental	An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 will be administered two weeks apart by intradermal injection. Receives: Biological: ATX-GD-59

What is being measured

The primary outcome is the main question the study is designed to answer.

Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.
An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug
Measured: 22 weeks

Secondary outcomes (9)

Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)
TSHR-binding inhibitory immunoglobulin (TBII) are autoantibodies directed against the TSH receptor. TBII is used clinically for the differential diagnosis and management of Graves' Disease.
Measured: Weeks 18, 22 and 30
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)
Stimulatory TSHR antibodies (TSAb) assays were measured using cell-based methods described by Leschik et al.
TSAb activity is measured by calculating percentage specimen-to-reference ratio (%SRR).
Measured: Weeks 18, 22 and 30
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)
Blocking TSHR antibodies (TBAb) assays were measured using cell-based methods described by Leschik et al.
TBAb activity is measured by calculating percentage inhibition.
Measured: Weeks 18, 22 and 30
Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.
Serum fT3 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT3 value at study day 1.
Measured: Weeks 18, 22 and 30
Change in Serum Free Thyroxine (T4) From Baseline to Week 22.
Serum fT4 was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
Measured: Weeks 18, 22 and 30
Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.
Serum TSH was measured centrally from screening to the final week 30 follow-up visit. Baseline was fT4 value at study day 1.
Measured: Weeks 18, 22 and 30
Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity
Measured: weeks 0, 18 and 22
Change From Baseline in IL-10 mRNA Expression in PBMCs
Measured: weeks 0, 18 and 22
Change From Baseline in Biomarker Signature of PBMC Cells
Measured: weeks 0, 18 and 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 201614 Feb 2018

First posted25 Nov 2016 (estimated)
Study startSep 2016
Primary completion14 Feb 2018
Study completion14 Feb 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Graves 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
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02973802
Sponsor's protocol ID: ATX-GD-59-001
Status last verified: Mar 2019
First submitted: 14 Nov 2016
Last updated: 14 Jun 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis
Thyroid Autoimmune Disease, Hashimoto's Thyroiditis
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease
Graves' Disease, Graves Disease
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease.
Graves Disease
Active, not recruitingPhase 4
Hydroxychloroquine in Mild Graves' Orbitopathy
Graves Ophthalmopathy
RecruitingPhase 2
A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease
Graves' Disease

All Graves Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Safety and Proof of Principle Study of ATX-GD-59 in Male and Female Subjects With Graves' Disease Not Currently Treated With Anti-thyroid Therapy: An Open Label Study, With an Upward Titration Over Five Dose Levels Administered by Intradermal Injection
ClinicalTrials.gov ID: NCT02973802
Acronym / sponsor ID: ATX-GD-59-001
Conditions: Graves Disease
Keywords: Graves Disease, Phase 1
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 12 participants (actual)
Lead sponsor: Apitope International NVIndustry (pharma, biotech, devices)
Collaborators: Quintiles, Inc., European Commission
Study start: Sep 2016 (actual)
Primary completion: 14 Feb 2018 (actual)
Study completion: 14 Feb 2018 (actual)
First posted: 25 Nov 2016 (estimated)
Results: Posted 14 Jun 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
ATX-GD-59 treatment	Experimental	Biological: ATX-GD-59An upward titration over five dose levels (25, 50, 100, 400 and 800 micrograms) followed by 5 doses of 800 micrograms of ATX-GD-59 will be administered two weeks apart by intradermal injection.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

A diagnosis of Graves' disease as assessed by a physician from clinical and laboratory findings and not receiving anti-thyroid therapy.
Quantifiable levels of TSHR antibodies.
Raised levels of free T3 and/or free T4 (not exceeding 15 pmol/L and 35 pmol/L respectively) including undetectable levels of thyroid stimulating hormone.
HLA-DRB1*15, HLA DRB1*03 and or HLA DRB1*04 positive.
Age 18 - 65 years inclusive at the time of informed consent.

Key exclusion criteria (19 listed)

Subjects who are pregnant or breastfeeding and/or subjects in the post-partum period.
A known history of, or hypersensitivity reactions that in the opinion of the investigator would exclude the subjects' participation in the study.
Treatment with any Anti-Thyroid Drugs eg carbimazole within the previous 3 months prior to Study Day 1.
Previous treatment with radioiodine or (partial or complete) thyroidectomy.
Signs of moderate or severe orbitopathy including optic nerve compression requiring steroids and/or a clinical activity score >3.

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
ATX-GD-59Disease specific immune modulating treatment for Graves Disease	Biological	ATX-GD-59 treatment

Primary outcome

Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.
Time frame: 22 weeks
An adverse event (AE) was defined as any untoward medical occurrence in a subject administered study drug that did not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavourable and unintended sign, symptom, disease or outcome of death temporally associated with the use of study drug, whether or not considered causally related to the study drug. Treatment emergent adverse events (TEAEs) were any AE that started or worsened in severity on or after the first administration of study drug up to and including 28 days after the last administration of study drug. Relationship, as indicated by the Investigator, was classified as 'not related', 'possibly related', 'probably related' or 'definitely related' (increasing severity of relationship). A drug related AE was defined as an AE with a relationship to study drug of 'possibly related', 'probably related' or 'definitely related' or with a missing or unknown relationship to study drug

9 secondary outcomes

Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by TSHR-binding Inhibitory Immunoglobulin (TBII)
Time frame: Weeks 18, 22 and 30
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Stimulatory TSHR Antibodies (TSAb)
Time frame: Weeks 18, 22 and 30
Change in Serum Anti-TSHR Antibodies From Baseline to Week 22 - Measured by Blocking TSHR Antibodies (TBAb)
Time frame: Weeks 18, 22 and 30
Change in Serum Free Triiodothyronine (fT3) From Baseline to Week 22.
Time frame: Weeks 18, 22 and 30
Change in Serum Free Thyroxine (T4) From Baseline to Week 22.
Time frame: Weeks 18, 22 and 30
Change in Serum Thyroid Stimulating Hormone (TSH) From Baseline to Week 22.
Time frame: Weeks 18, 22 and 30
Change From Baseline in Peripheral Blood Mononuclear Cell (PBMC) T Cell Activity
Time frame: weeks 0, 18 and 22
Change From Baseline in IL-10 mRNA Expression in PBMCs
Time frame: weeks 0, 18 and 22
Change From Baseline in Biomarker Signature of PBMC Cells
Time frame: weeks 0, 18 and 22

Results and safety

Results posted to the registry on 14 Jun 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
ATX-GD-59 Treatment	12	10

Primary outcome: Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline.

Time frame: 22 weeks. Number. Unit: Adverse Events

Measure	ATX-GD-59 Treatment n = 12
Total Adverse Events	311
Mild Adverse Events	293
Moderate Adverse Events	18
Severe Adverse Events	0
Drug Related Adverse Events	180
Total Serious Adverse Events	3
Drug Related Serious Events	1
Adverse Events leading to death	0

Population analysed: The Intention-to-treat population corresponded to all subjects who received at least 1 administration of study drug at any time during the study, irrespective of compliance with eligibility and other protocol criteria. The Safety population was denoted as the 'Intention-to-treat population' for the summarisation of safety endpoints.

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded from screening through to the final follow up visit at week 30.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Emergent Adverse Events	1 of 12 (8.3%)	11 of 12 (91.7%)	0 of 12
Non Treatment Emergent Adverse Events	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Related trials for Graves Disease

Not yet recruiting
Impact of Restrictive Diets on Inflammation and Quality of Life in Autoimmune Thyroiditis
Thyroid Autoimmune Disease, Hashimoto's Thyroiditis
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease
Graves' Disease, Graves Disease
RecruitingPhase 3
A Study to Assess Efficacy and Safety of Efgartigimod PH20 SC PFS in Adult Participants With Graves' Disease.
Graves Disease
Active, not recruitingPhase 4
Hydroxychloroquine in Mild Graves' Orbitopathy
Graves Ophthalmopathy
RecruitingPhase 2
A Study to Assess the Efficacy, Safety, and Tolerability of IMVT-1402 as Treatment for Adult Participants With Graves' Disease
Graves' Disease

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.

Simon HS Pearce principal investigator

Royal Victoria Infirmary

8 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ATX-GD-59 in people with Graves Disease, run by Apitope International NV at 8 sites 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 14 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites 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?

Yes. Results are posted in the registry (first posted 14 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Occurrence of Treatment Emergent Adverse Events (TEAE), Serious Adverse Events (SAE), and Laboratory Abnormalities up to Week 22 Compared to Baseline. (time frame: 22 weeks). 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 NCT02973802.

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 14 Jun 2019.