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Trial record 1 of 1 for:    KY1005 | psoriasis
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A Study of KY1005 in Healthy Volunteers and Volunteers With Psoriasis

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Kymab Limited
Sponsor:
Information provided by (Responsible Party):
Kymab Limited
ClinicalTrials.gov Identifier:
NCT03161288
First received: May 11, 2017
Last updated: August 1, 2017
Last verified: August 2017
  Purpose
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 and volunteers with mild-to-moderate plaque psoriasis.

Condition Intervention Phase
Immune System Diseases Drug: KY1005 Drug: Placebo Phase 1

Study Type: Interventional
Study Design: 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 and Volunteers With Psoriasis

Resource links provided by NLM:


Further study details as provided by Kymab Limited:

Primary Outcome Measures:
  • Occurrence of all treatment-related adverse events [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]
  • 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 10: from pre- first infusion up to day 85. ]
  • 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 10: from pre-first infusion up to day 85. ]
  • 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 10: from pre-first infusion up to day 85. ]
  • 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 10: from pre-first infusion up to day 85. ]
  • 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 10: from pre-first infusion up to day 85. ]

Secondary Outcome Measures:
  • 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 10: up to day 85. ]
  • 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 10: up to day 85. ]
  • 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 10: up to day 85. ]
  • Areas under the plasma concentration-time curves (AUC) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]
  • Clearance (CL) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]
  • Apparent volume of distribution during terminal phase (Vz) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]
  • Apparent volume of distribution at steady state (Vss) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]
  • Half-life (t½) [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]

Other Outcome Measures:
  • Serum anti-KY1005 antibody titres [ Time Frame: Cohorts 1 to 3: up to day 113. Cohorts 4 to 10: up to day 85. ]
    Change in serum anti-KY1005 antibody titres from pre-infusion.

  • Immunophenotype and OX40/OX40L expression [ Time Frame: Cohorts 1- 10: up to day 85. ]
    Changes in specific cell subsets and expression of OX40/OX40L on each subset (where evaluable).

  • 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.

    Change in ex vivo peripheral blood mononuclear cell responses to tetanus toxoid exposure and Immucothel® exposure.


  • Serum cytokines (chronic) (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Change in serum cytokines.

  • Body surface area (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Change in the percent of total body surface area involved with plaque psoriasis.

  • PASI (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Percentage change in Psoriasis Area and Severity Index

  • Target lesion assessment (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Mean change in target lesion assessment.

  • Physician's Global Assessment score (Cohorts 9 & 10 only) [ Time Frame: Day 85 ]
    Proportion of volunteers achieving a Physician's Global Assessment (PGA) of 0 or 1

  • Skin biopsies (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Change in immunohistochemistry and biomarker analysis in skin biopsies

  • Digital PASI (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Change in digital PASI (PASI derived from total body photography for automatic quantification of psoriatic lesions).

  • Transdermal analyses patch (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Change in skin surface biomarkers will be measured via transdermal analyses patch from a target lesion.

  • Dermatology Life Quality Index (DLQI) (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Mean change in DLQI

  • Numerical rating scale (NRS) pruritus (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Mean change in NRS pruritus

  • Numerical rating scale (NRS) sleep loss (Cohorts 9 & 10 only) [ Time Frame: up to day 85 ]
    Mean change in NRS sleep loss


Estimated Enrollment: 88
Actual Study Start Date: May 29, 2017
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Experimental: Cohorts 9 & 10
Volunteers with psoriasis will receive multiple rising doses of KY1005 or placebo
Drug: KY1005
A human anti-OX40 ligand monoclonal antibody
Drug: Placebo
Matched placebo

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Healthy male volunteers. Males or females of non-childbearing potential with mild-to-moderate plaque psoriasis.
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. Cohorts 1 to 8: Male, aged 18 to 45 years.
  3. Cohorts 9 and 10: Male, or female of non-childbearing potential, aged 18 to 65 years.
  4. 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.
  5. 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.
  6. Cohorts 4 to 8: anti-TT immunoglobulin G (IgG) response > 0.1 IU/mL and ≤ 50 IU/mL at screening.
  7. Cohorts 9 and 10: diagnosed with mild to moderate plaque psoriasis at least 6 months prior to administration of Investigational Medicinal Product (IMP) and not on systemic treatment, ≥ 5% body surface area involvement, ≥ 2 plaques suitable for repeat biopsy and target lesion assessments. Volunteers must be willing to stop any other psoriasis therapy other than emollients and the principal investigator (or medically qualified designee) must be satisfied that if pre-study therapy is stopped, the volunteer will not be significantly disadvantaged.

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. For healthy volunteers, body weight of ≤ 60.0 kg or ≥ 120.0 kg. For psoriasis volunteers, body weight of ≤ 60.0 kg or ≥ 125.0 kg.
  3. A body mass index ≤ 18.0 or ≥ 30.0 kg/m2 (35.0 kg/m2 for psoriasis volunteers).
  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 × 109/L or > 9.50 × 109/L, neutrophil absolute value < 1.8 × 109/L, platelet counts < 100 × 109/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. Cohorts 1 to 8: prescription drug taken within 2 weeks of screening or likely to be taken during the trial.
  11. Cohorts 9 and 10: prescription medicines that are considered by the principal investigator (or medically qualified designee) to either put the volunteer at risk if taken during the study or are likely to interfere with the scientific integrity of the study.
  12. 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.
  13. 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.
  14. Hepatitis B surface antigen, Hepatitis C antibody, or Human Immunodeficiency Virus positive.
  15. History of or current drug or substance abuse considered significant by the principal investigator (or medically qualified designee) including a positive urine drug screen.
  16. Current smoker and/or regular user of other nicotine-containing products (e.g., patches).
  17. Average consumption of more than 14 units of alcohol/week.
  18. 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).
  19. Cannot communicate adequately or cannot commit to full participation in all trial procedures.
  20. 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.
  21. For Cohorts 9 and 10:

    1. Use of therapeutic drugs targeted against interleukin-12 (IL-12), IL-17, or IL-23, or experimental agents within 6 months, or any approved biologic agent 3 months prior to study drug administration;
    2. Phototherapy, systemic therapies, or immunosuppressants within 1 month, or topical treatments within 2 weeks of baseline Psoriasis Area and Severity Index (PASI) assessments.
  22. Any observation that, in the opinion of the principal investigator (or medically qualified designee) makes the subject unsuitable for participation in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

Responsible Party: Kymab Limited
ClinicalTrials.gov Identifier: NCT03161288     History of Changes
Other Study ID Numbers: KY1005-CT01
Study First Received: May 11, 2017
Last Updated: August 1, 2017
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:
Psoriasis
Immune System Diseases
Skin Diseases, Papulosquamous
Skin Diseases

ClinicalTrials.gov processed this record on August 18, 2017