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A Study of KY1005 in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT03161288
Recruitment Status : Recruiting
First Posted : May 19, 2017
Last Update Posted : February 1, 2018
Sponsor:
Information provided by (Responsible Party):
Kymab Limited

Brief Summary:
This is a single and multiple ascending dose, placebo-controlled, double-blind, Phase 1 study to evaluate the safety and tolerability of KY1005 in healthy volunteers.

Condition or disease Intervention/treatment Phase
Immune System Diseases Drug: KY1005 Drug: Placebo Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Single and Multiple Ascending Dose, Placebo-Controlled, Double-Blind, Phase 1 Study of KY1005 in Healthy Volunteers
Actual Study Start Date : May 29, 2017
Estimated Primary Completion Date : March 2018
Estimated Study Completion Date : March 2018

Arm Intervention/treatment
Experimental: Cohorts 1-3
Healthy volunteers will receive single rising doses of KY1005 or placebo
Drug: KY1005
A human anti-OX40 ligand monoclonal antibody
Drug: Placebo
Matched placebo
Experimental: Cohorts 4-8
Healthy volunteers will receive multiple rising doses of KY1005 or placebo
Drug: KY1005
A human anti-OX40 ligand monoclonal antibody
Drug: Placebo
Matched placebo



Primary Outcome Measures :
  1. Occurrence of all treatment-related adverse events [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  2. Changes in vital signs (as a measure of safety and tolerability) [ Time Frame: Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre- first infusion up to day 92. ]
  3. Changes in laboratory safety data (as a measure of safety and tolerability) [ Time Frame: Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. ]
  4. Changes in anti-viral antibody levels and viral DNA (as a measure of safety and tolerability) [ Time Frame: Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. ]
  5. Changes in acute cytokines (as a measure of safety and tolerability) [ Time Frame: Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. ]
  6. Changes in electrocardiograms (as a measure of safety and tolerability) [ Time Frame: Cohorts 1 to 3: from pre-first infusion up to day 113. Cohorts 4 to 8: from pre-first infusion up to day 92. ]

Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) following the first, second and third infusions for each KY1005 dose/dosing group [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  2. Time to maximum observed serum concentration (tmax) following the first, second and third infusions for each KY1005 dose/dosing group [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  3. Trough concentrations (Cmin) following the first and second infusions and 28 days after the third infusion [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  4. Areas under the plasma concentration-time curves (AUC) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  5. Clearance (CL) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  6. Apparent volume of distribution during terminal phase (Vz) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  7. Apparent volume of distribution at steady state (Vss) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
  8. Half-life (t½) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]

Other Outcome Measures:
  1. Serum anti-KY1005 antibody titres [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 8: up to day 92. ]
    Change in serum anti-KY1005 antibody titres from pre-infusion.

  2. Immunophenotype and OX40/OX40L expression [ Time Frame: Cohorts 1- 8: up to day 85. ]
    Changes in specific cell subsets and expression of OX40/OX40L on each subset (where evaluable).

  3. Neo-antigen and recall antigen immunological responses (cohorts 4-8 only) [ Time Frame: up to day 85 ]
    Change in anti-tetanus toxoid immunoglobulin G (IgG) and immunoglobulin M (IgM) titres in serum and anti-Immucothel® IgG and IgM titres in serum.

  4. Delayed Type Hypersensitivity response in the skin after intradermal injection of Immucothel® or saline measured by Antera 3D® camera image analysis (cohorts 4-8 only) [ Time Frame: Day 85 and 87 ]
    Change in skin colour a and haemoglobin level (concentration of redness per unit area relative to region of interest)

  5. Delayed Type Hypersensitivity response in the skin after intradermal injection of Immucothel® or saline measured by LSCI photography (cohorts 4-8 only) [ Time Frame: Day 85 and 87 ]
    Change in basal flow and flare



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Healthy male volunteers.
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects must fulfil all of the following criteria for entry into the study.

  1. Volunteer to participate in the clinical trial and provide signed informed consent.
  2. Male, aged 18 to 45 years.
  3. Subjects with a female spouse/partner of childbearing potential must agree to use effective birth control starting at screening and continuing throughout the clinical study period and for a period of up to 6 months after study completion.
  4. Cohorts 4 to 8: previous immunisation with tetanus toxoid (TT) but not within 6 months prior to the screening visit as reported by the volunteer.
  5. Cohorts 4 to 8: anti-TT immunoglobulin G (IgG) response > 0.1 IU/mL and ≤ 50 IU/mL at screening.

Exclusion Criteria:

Subjects fulfilling any of the following exclusion criteria are not eligible for entry into the study.

  1. Experiencing a clinically significant, chronic or acute infection requiring treatment at screening or prior to first IMP administration.
  2. A body weight of ≤ 60.0 kg or ≥ 120.0 kg.
  3. A body mass index ≤ 18.0 or ≥ 30.0 kg/m2.
  4. History of disease of the central nervous system, cardiovascular system, kidney, liver, digestive system, respiratory system or metabolic/endocrine system or suffered from other disease that in the opinion of the principal investigator (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations or otherwise considered clinically significant.
  5. History of immunological abnormality (e.g., immune suppression, severe allergy or anaphylaxis) that in the opinion of the principal investigator (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations or otherwise considered clinically significant.
  6. History of malignancy, or known current malignancy.
  7. Leukocyte absolute value < 3.50 × 10^9/L or > 9.50 × 10^9/L, neutrophil absolute value < 1.8 × 10^9/L, platelet counts < 100 × 10^9/L, haemoglobin < 12.0 g/dL.
  8. Taken part in other clinical trials within 3 months of screening for this study or > four trials in the year preceding the first IMP administration.
  9. Donated or lost more than 500 mL of blood or plasma within 3 months of screening.
  10. Prescription drug taken within 2 weeks of screening or likely to be taken during the trial.
  11. Live immunisation within 3 months of screening or plans to receive such immunisation during the clinical trial or for a period of 6 months after the end of the trial.
  12. Taking or likely to take over-the-counter medication, including herbal medicines, that in the opinion of the principal investigator (or medically qualified designee) may make participation unsafe for the subject or interfere with trial evaluations.
  13. Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus positive.
  14. History of or current drug or substance abuse considered significant by the principal investigator (or medically qualified designee) including a positive urine drug screen.
  15. Current smoker and/or regular user of other nicotine-containing products (e.g., patches).
  16. Average consumption of more than 14 units of alcohol/week.
  17. Clinically significant abnormal screening values in clinical (electrocardiograms (ECGs), vital signs, physical examination) and laboratory tests in the opinion of the principal investigator (or medically qualified designee).
  18. Cannot communicate adequately or cannot commit to full participation in all trial procedures.
  19. For Cohorts 4 to 8:

    1. Confirmed previous exposure to immunocyanins, such as keyhole limpet haemocyanin (KLH);
    2. Known allergy to thiomersal or other components of Tetanus vaccine or Immucothel®;
    3. History of schistosomiasis.
  20. Any observation that, in the opinion of the principal investigator (or medically qualified designee) makes the subject unsuitable for participation in this study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03161288


Contacts
Contact: Medical Officer +44 (0) 1223 833301 clinicaltrial@kymab.com

Locations
Netherlands
Centre for Human Drug Research Recruiting
Leiden, Netherlands
Sponsors and Collaborators
Kymab Limited
Investigators
Principal Investigator: Jacobus Burggraaf Centre for Human Drug Research

Responsible Party: Kymab Limited
ClinicalTrials.gov Identifier: NCT03161288     History of Changes
Other Study ID Numbers: KY1005-CT01
First Posted: May 19, 2017    Key Record Dates
Last Update Posted: February 1, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Immune System Diseases