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NCT Number: NCT02904330

K1-70 - A 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.

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Key information

Conditions

Graves' Disease Autoimmune Diseases Endocrine System Diseases Exophthalmos Eye Diseases Goiter Graves Disease Hyperthyroidism Immune System Diseases Orbital Diseases Thyroid Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Royal Liverpool University Hospital Clinical Research Unit, Liverpool, United Kingdom

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

K1-70 intramuscular or K1-70 intravenous

Drug

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.

Primary outcomes

  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.

    Time frame: Over a period of 18 weeks

    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.

Secondary outcomes

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

    Time frame: Over a period of 18 weeks

    The terminal elimination rate constant will be calculated and reported

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

    Time frame: Over a period of 18 weeks

    The terminal elimination half life will be calculated and reported

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

    Time frame: Over a period of 18 weeks

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

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

    Time frame: Over a period of 18 weeks

    Maximum observed plasma concentration will be calculated and reported

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

    Time frame: Over a period of 18 weeks

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

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

    Time frame: Over a period of 18 weeks

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

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

    Time frame: Over a period of 18 weeks

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

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

    Time frame: Over a period of 18 weeks

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

  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

    Time frame: Over a period of 18 weeks

    TSH levels will be measured and reported over time.

  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

    Time frame: Over a period of 18 weeks

    Free T3 levels will be measured and reported over time.

  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

    Time frame: Over a period of 18 weeks

    Free T4 levels will be measured and reported over time.

Other outcomes

  1. Exploratory Objective: Thyroid hormones will be measured over time and their correlation to baseline TSH receptor autoantibody (TRAb) levels will be reported at different time points

    Time frame: Over a period of 18 weeks

    TSH levels will be reported against baseline TRAb over time.

  2. Exploratory Objective: Thyroid hormones will be measured over time and their correlation to baseline TSH receptor autoantibody (TRAb) levels will be reported at different time points

    Time frame: Over a period of 18 weeks

    Free T3 levels will be reported against baseline TRAb over time.

  3. Exploratory Objective: Thyroid hormones will be measured over time and their correlation to baseline TSH receptor autoantibody (TRAb) levels will be reported at different time points

    Time frame: Over a period of 18 weeks

    Free T4 levels will be reported against baseline TRAb over time.

  4. Exploratory Objective: The potential effect of K1-70 on Graves' ophthalmopathy will be measured by eye examinations using the Clinical Activity Score (CAS) system.

    Time frame: Over a period of 18 weeks

    All clinically significant results and the number of treatment related adverse events will be reported.

Sponsors and collaborators

Lead sponsor

AV7 Limited

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Sep 16, 2016
Registry last updated
May 20, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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