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Graves' DiseasePhase 1NCT02904330

K1-70 - A Study in Subjects With Graves' Disease

A Phase 1 study testing K1-70 intramuscular or K1-70 intravenous in people with Graves' Disease, run by AV7 Limited at 2 sites in United Kingdom.

Completed

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

Official record
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Trial summary

This study is the first time that K1-70 will be administered to humans. The principal aim of this study is to obtain safety and tolerability data when K1-70 is administered as an IM injection or as an IV infusion to subjects with Graves' disease. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Graves' Disease
What is being tested?
K1-70 intramuscular or K1-70 intravenous
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
2 sitesUnited Kingdom
Study dates
Aug 2016to Apr 2021
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Main Inclusion Criteria:

  • age 18-75 years
  • have Graves' disease and are being treated with anti-thyroid medications OR not treated with anti-thyroid medications (due to side-effects) and who are clinically and biochemically euthyroid or hyperthyroid
  • have a body mass index (weight [kg]/height [m]2) between 18.5 and 35.0 kg/m2

Main Exclusion Criteria:

  • current or chronic history of liver disease
  • history of cancer within the last 5 years except localised skin cancer
  • Graves' orbitopathy with clinical activity score >3/7
  • evidence of optic neuropathy and/or corneal breakdown
  • significant systemic infection
  • history of recurrent or current infection
  • splenectomy
  • recently had major surgery or plan major surgery
  • had thromboembolic event due to a blood clot in the last 12 months
  • have clinically significant laboratory tests
  • a clinically significant allergic condition (excluding hay fever)
  • currently receiving corticosteroids
  • smoke more than 10 cigarettes (or its equivalent in nicotine (including use of e-cigarettes)) per day
  • history of drug abuse

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

  • Royal Liverpool University Hospital Clinical Research Unit

    Liverpool, L7 8XP

  • Medicines Evaluation Unit

    Manchester, M23 9QZ

Other trials in United Kingdom

About this study

Official title: K1-70 - A Phase I, Single Ascending Intramuscular Dose or Single Ascending Intravenous Dose, Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study in Subjects With Graves' Disease

This study is the first time that K1-70 will be administered to humans. The principal aim of this study is to obtain safety and tolerability data when K1-70 is administered as an IM injection or as an IV infusion to subjects with Graves' disease.

Current therapy for Graves' disease includes treatment with anti-thyroid drugs, destruction of the thyroid using radioiodine, or total surgical thyroidectomy. Beta-blockers and calcium antagonists may be used to control some of the symptoms of hyperthyroidism.

K1-70 is a thyroid stimulating hormone receptor antagonist that may provide new in vivo diagnostic and therapeutic tools for the management of patients with Graves' disease, patients with thyroid cancer and patients who would benefit from controlling receptor activity.

Read the detailed description

Graves' disease is one of the most common overt autoimmune disorders. Patients with Graves' disease have thyroid over activity and hyperthyroidism. Symptoms of hyperthyroidism include goitre, fatigue, heat intolerance, sweating, weight loss despite good appetite, shakiness, inappropriate anxiety, palpitations of the heart, shortness of breath, tetchiness and agitation, poor sleep, thirst, nausea and increased frequency of defaecation.

The rationale of this study is to obtain safety and tolerability data when K1-70 is administered as an intramuscular injection or as an IV infusion to subjects with Graves' disease.

This information, together with the pharmacokinetic data, will help establish the doses and dosage regimen suitable for repeat administration to patients.

This is an open-label study. The expected duration of each subject's participation in the study is approximately 18 weeks (including a screening period of up to 4 weeks).

Conditions
Graves' Disease
Being tested
K1-70 intramuscular or K1-70 intravenous
Medical subject headings
Graves Disease

What participants receive

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

  • K1-70 intramuscular or K1-70 intravenousDrug

    Each subject will receive one dose of K1-70 by IM injection or one dose of K1-70 by IV infusion on the morning of Day 1.

Study groups in NCT02904330
Study groupRoleWhat they receive
Single doseExperimentalThe intervention is K1-70 intramuscular or K1-70 intravenous. This is a single, ascending, intramuscular or intravenous dose, sequential group study.
Receives: Drug: K1-70 intramuscular or K1-70 intravenous

What is being measured

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

  1. Safety and tolerability will be measured using vital signs, ECG, blood samples for haematology, coagulation, clinical biochemistry and hormone panel, urinalysis, eye examinations, physical examinations and examination of injection or infusion site.

    Safety and tolerability testing consists of vital signs, ECG, blood samples for haematology, coagulation, clinical biochemistry and hormone panel, urine samples for urinalysis, eye examinations, physical examinations and examination of injection or infusion site. All clinically significant results and the number of treatment related adverse events will be reported.

    Measured: Over a period of 18 weeks

Secondary outcomes (11)

  1. The concentration of K1-70 drug in the blood will be measured over time.

    The terminal elimination rate constant will be calculated and reported

    Measured: Over a period of 18 weeks

  2. The concentration of K1-70 drug in the blood will be measured over time.

    The terminal elimination half life will be calculated and reported

    Measured: Over a period of 18 weeks

  3. The concentration of K1-70 drug in the blood will be measured over time.

    Time of the maximum observed plasma concentration will be calculated and reported

    Measured: Over a period of 18 weeks

  4. The concentration of K1-70 drug in the blood will be measured over time.

    Maximum observed plasma concentration will be calculated and reported

    Measured: Over a period of 18 weeks

  5. The concentration of K1-70 drug in the blood will be measured over time.

    Area under the plasma concentration time curve to the last quantified concentration will be calculated and reported

    Measured: Over a period of 18 weeks

  6. The concentration of K1-70 drug in the blood will be measured over time.

    Area under the plasma concentration time curve from time zero to infinity will be calculated and reported

    Measured: Over a period of 18 weeks

  7. The concentration of K1-70 drug in the blood will be measured over time.

    Percentage of area under the plasma concentration time curve that is extrapolated will be calculated and reported

    Measured: Over a period of 18 weeks

  8. The antidrug antibodies will be measured to evaluate the immunogenic potential of K1-70 in Graves' disease patients

    The level of antidrug antibodies present in the patient serum will be measured over time and reported.

    Measured: Over a period of 18 weeks

  9. The effect of a single IM dose or single IV dose of K1-70 on thyroid activity in subjects with Graves' will be measured over time

    TSH levels will be measured and reported over time.

    Measured: Over a period of 18 weeks

  10. The effect of a single IM dose or single IV dose of K1-70 on thyroid activity in subjects with Graves' will be measured over time

    Free T3 levels will be measured and reported over time.

    Measured: Over a period of 18 weeks

  11. The effect of a single IM dose or single IV dose of K1-70 on thyroid activity in subjects with Graves' will be measured over time

    Free T4 levels will be measured and reported over time.

    Measured: Over a period of 18 weeks

Timeline

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

  1. First posted16 Sep 2016 (estimated)
  2. Study startAug 2016
  3. Primary completionApr 2021
  4. Study completionApr 2021

Resources

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
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02904330
Sponsor's protocol ID
K1im001
Status last verified
May 2021
First submitted
18 Aug 2016
Last updated
20 May 2021
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Evans M, Sanders J, Tagami T, Sanders P, Young S, Roberts E, Wilmot J, Hu X, Kabelis K, Clark J, Holl S, Richards T, Collyer A, Furmaniak J, Smith BR. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf). 2010 Sep;73(3):404-12. doi: 10.1111/j.1365-2265.2010.03831.x. Epub 2010 Jun 9.

    PubMed 20550534

  • Sanders P, Young S, Sanders J, Kabelis K, Baker S, Sullivan A, Evans M, Clark J, Wilmot J, Hu X, Roberts E, Powell M, Nunez Miguel R, Furmaniak J, Rees Smith B. Crystal structure of the TSH receptor (TSHR) bound to a blocking-type TSHR autoantibody. J Mol Endocrinol. 2011 Feb 15;46(2):81-99. doi: 10.1530/JME-10-0127. Print 2011 Apr.

    PubMed 21247981

  • Furmaniak J, Sanders J, Young S, Kabelis K, Sanders P, Evans M, Clark J, Wilmot J, Rees Smith B. In vivo effects of a human thyroid-stimulating monoclonal autoantibody (M22) and a human thyroid-blocking autoantibody (K1-70). Auto Immun Highlights. 2011 Sep 14;3(1):19-25. doi: 10.1007/s13317-011-0025-9. eCollection 2012 Apr.

    PubMed 26000124

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing K1-70 intramuscular or K1-70 intravenous in people with Graves' Disease, run by AV7 Limited at 2 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?

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 20 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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?

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 will be measured using vital signs, ECG, blood samples for haematology, coagulation, clinical biochemistry and hormone panel, urinalysis, eye examinations, physical examinations and examination of injection or infusion site. (time frame: Over a period of 18 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 NCT02904330, which also lists 3 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 20 May 2021.

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