Clinical Trial: K1-70 - A Study in Subjects With Graves' Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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 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.


Detailed Summary:

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 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).


Sponsor: AV7 Limited

Current Primary Outcome: 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 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 site. All clinically significant results and the number of treatment related adverse events will be reported.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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.
  • The effect of a single IM 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.
  • The effect of a single IM 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.
  • The effect of a single IM 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.


Original Secondary Outcome: Same as current

Information By: AV7 Limited

Dates:
Date Received: August 18, 2016
Date Started: July 2016
Date Completion: April 2017
Last Updated: October 14, 2016
Last Verified: August 2016