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

NCT ID: NCT02904330

Last Updated: 2021-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2021-04-30

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).

Conditions

Graves' Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single dose

The intervention is K1-70 intramuscular or K1-70 intravenous. This is a single, ascending, intramuscular or intravenous dose, sequential group study.

Group Type: EXPERIMENTAL

K1-70 intramuscular or K1-70 intravenous

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AV7 Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dave Singh, Professor

Role: PRINCIPAL_INVESTIGATOR

Medicines Evaluation Unit, Manchester, UK

Locations

Royal Liverpool University Hospital Clinical Research Unit

Liverpool, , United Kingdom

Medicines Evaluation Unit

Manchester, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 20550534 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21247981 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26000124 (View on PubMed)

Other Identifiers

K1im001

Identifier Type: -

Identifier Source: org_study_id