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

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ClinicalTrials.gov Identifier: NCT02904330
Recruitment Status : Recruiting
First Posted : September 16, 2016
Last Update Posted : August 5, 2019
Sponsor:
Information provided by (Responsible Party):
AV7 Limited

Tracking Information
First Submitted Date  ICMJE August 18, 2016
First Posted Date  ICMJE September 16, 2016
Last Update Posted Date August 5, 2019
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 15, 2016)
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.
Change History Complete list of historical versions of study NCT02904330 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2019)
  • 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 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 15, 2016)
  • 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.
Current Other Pre-specified Outcome Measures
 (submitted: September 15, 2016)
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE K1-70 - A Study in Subjects With Graves' Disease
Official Title  ICMJE 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
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 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.

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).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Graves' Disease
Intervention  ICMJE Drug: K1-70 intramuscular or K1-70 intravenous
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 Arms  ICMJE Experimental: Single dose
The intervention is K1-70 intramuscular or K1-70 intravenous. This is a single, ascending, intramuscular or intravenous dose, sequential group study.
Intervention: Drug: K1-70 intramuscular or K1-70 intravenous
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 15, 2016)
36
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2020
Estimated Primary Completion Date February 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: MEU +44 (0)161 946 4050 304@meu.org.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02904330
Other Study ID Numbers  ICMJE K1im001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party AV7 Limited
Study Sponsor  ICMJE AV7 Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Dave Singh, Professor Medicines Evaluation Unit, Manchester, UK
PRS Account AV7 Limited
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP