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Trial record 16 of 117 for:    "Connective Tissue Disease" | "Methylprednisolone"

Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT03368235
Recruitment Status : Recruiting
First Posted : December 11, 2017
Last Update Posted : June 20, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Brief Summary:
This is a phase 2a study to be run in 2-3 countries in European Union involving 5-6 sites. It will enroll approximately 80 patients to ensure 40 randomized with active rheumatoid arthritis. The treatment period is 2 weeks and total study duration per patient is approximately 1 month. The study drugs are AZD9567 40 mg (an oral SGRM) and the comparator is prednisolone 20mg. The primary endpoint is DAS28 including evaluation of 28 joints and C-reactive protein. Safety parameters will also be evaluated and a biomarker program is included for future research.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: AZD9567 Drug: Prednisolone Phase 2

Detailed Description:

This randomized double blind with double dummy technique phase 2a study will be run in 2-3 EU countries, most likely Sweden, Denmark and The Netherlands involving 5-6 sites. It is estimated that 80-100 patients have to be enrolled to ensure the randomization target of 40. The study population is patients with rheumatoid arthritis on stable treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) with an active flare. It is a two-arm parallel study and the randomization ratio is 1:1 to the two weeks of once daily treatment of 40 mg of AZD9567 and 20 mg prednisolone.

The primary objective is to assess the efficacy of AZD9567 40 mg, compared to prednisolone 20 mg in patients with active rheumatoid arthritis in spite of stable treatment with conventional and/or s.c/i.v. biological DMARDs and the primary variable is change from baseline in 28 joint Disease Activity Score using CRP (DAS28 - CRP). As secondary variables swollen and tenderness of 66-68 joints and safety variables are also included. For exploratively purposes there is also a biomarker program, collecting blood samples for future research.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, double blind, parallell arm study with two weeks treatment of AZD9567 or prednisolone
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double dummy technique
Primary Purpose: Treatment
Official Title: A Phase 2a, Randomised, Double-blind, Parallel Study to Assess the Efficacy, Safety and Tolerability of AZD9567 Compared to Prednisolone 20 mg in Patients With Active Rheumatoid Arthritis (RA)
Actual Study Start Date : January 18, 2018
Estimated Primary Completion Date : September 17, 2020
Estimated Study Completion Date : September 17, 2020


Arm Intervention/treatment
Experimental: AZD9567
oral suspension of 40 mg AZD9567 once daily (OD) for two weeks
Drug: AZD9567
oral OD SGRM administered as suspension

Active Comparator: Prednisolone
oral OD treatment of 20 mg prednisolone administered as capsules
Drug: Prednisolone
oral capsules of 20 mg prednisolone administered OD for two weeks




Primary Outcome Measures :
  1. • Change from baseline in 28 joint Disease Activity Score using CRP (DAS 28 - CRP) [ Time Frame: Two weeks ]
    From start of treatment (randomization visit, Visit 2) to end of treatment (Visit 5), which occurs after two weeks.


Secondary Outcome Measures :
  1. • Proportion of subjects reaching ACR (American College of Rheumatology) 20, 50 and 70 responses [ Time Frame: Two weeks ]
    From start of treatment (randomization visit, Visit 2) to end of treatment (Visit 5), which occurs after two weeks.

  2. • Change from baseline in Swollen Joint Count 66 (SJC 66) [ Time Frame: Two weeks ]
    From start of treatment (randomization visit, Visit 2) to end of treatment (Visit 5), which occurs after two weeks.

  3. • Change from baseline in Tender Joint Count 68 (TJC 68) [ Time Frame: Two weeks ]
    From start of treatment (randomization visit, Visit 2) to end of treatment (Visit 5), which occurs after two weeks.

  4. Area under the plasma concentration curve (AUC) of AZD9567 and prednisolone, AUC 0-6 [ Time Frame: Up to a maximum of 24 hours ]
    Area under the plasma concentration curve from 0 to 6 h sample (area under the curve, AUC). Blood samples are collected pre dose and post dose during a 6 hour period at Visit 5.

  5. Pharmacokinetics (PK) of AZD9567 and prednisolone AUC (0-last) [ Time Frame: Up to a maximum of 24 hours ]
    Area under the plasma concentration curve from first to last sample. Blood samples are collected pre dose and post dose during a 6 hour period at Visit 5

  6. Pharmacokinetics (PK) of AZD9567 and prednisolone Tmax [ Time Frame: Up to a maximum of 24 hours ]
    Time to the maximum plasma concentration. Blood samples are collected pre dose and post dose during a 6 hour period at Visit 5

  7. PK of AZD9567 and prednisolone, Cmin [ Time Frame: Pre dose at steady state and two weeks (Visit 5) ]
    Predose sample at Visit 5 which is the end of treatment visit occuring after 2 weeks treatment.


Other Outcome Measures:
  1. Number of participants with Adverse events, as assessed by seriousness and severity [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring; (Adverse events, vital signs, ECG and laboratory parameters)

  2. Blood pressure in mmHg [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring; (Adverse events, vital signs, ECG and laboratory parameters)

  3. Pulse, in beats per minute [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring; (Adverse events, vital signs, ECG and laboratory parameters)

  4. Number of participants with normal or abnormal ECGs [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring; (Adverse events, vital signs, ECG and laboratory parameters)

  5. Change in hematology lab parameters (Hb, Leukocytes and platelets) [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring to identify any significant changes in order to detect safety concerns

  6. Change in clinical chemistry lab parameters (e g electrolytes, liver enzymes and lipids) [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring to identify any significant changes in order to detect safety concerns

  7. Change in urine lab parameters (e g Hemoglobin, glucose and protein) [ Time Frame: Up to a maximum of 6 weeks ]
    As part of standard safety monitoring to identify any significant changes in order to detect safety concerns



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Established RA diagnosis according to the 2010 American College of Rheumatology (ACR)/EULAR classification or the 1987 criteria
  2. Active RA (DAS28-CRP score ≥ 3.2) with at least 3 swollen joints and 3 tender joints using the DAS28 joint count
  3. Patients must have be on stable dosing of conventional and/or s.c./i.v biological DMARDs for the last 8 weeks prior to Visit 1
  4. CRP levels >5mg/L at screening if seronegative for Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide antibody (anti-CCP Ab), or >2mg/L if seropositive for either marker
  5. BMI between 18 and 35 (inclusive)
  6. Negative pregnancy test (serum) for female subjects of childbearing potential

Exclusion Criteria:

  1. History or current inflammatory rheumatic disease other than RA (secondary Sjogren's syndrome excluded)
  2. History or current clinically important disease which may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study
  3. Any clinical contraindications to treatment with steroids
  4. Oral or parenteral steroids (beyond study medication) 8 weeks prior to study start and during the study. Stable use and dose of topical and inhaled steroids for longer than 4 w prior to randomization is acceptable
  5. Use of any prohibited medication during the study or if the required washout time of such medication was not adhered to
  6. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar class to study drugs
  7. Any concomitant medications that are known to be associated with Torsades de Pointes

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): NCT03368235


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Denmark
Research Site Withdrawn
Frederiksberg, Denmark, 2000
Netherlands
Research Site Recruiting
Amsterdam, Netherlands, 1056 AB
Research Site Recruiting
Enschede, Netherlands, 7512 KZ
Research Site Recruiting
Maastricht, Netherlands, 6229 HX
Research Site Withdrawn
Roosendaal, Netherlands, 4707 CH
Research Site Recruiting
Utrecht, Netherlands, 3584 CW
Sweden
Research Site Recruiting
Göteborg, Sweden, 413 45
Research Site Recruiting
Lund, Sweden, 221 85
Research Site Recruiting
Uppsala, Sweden, 751 85
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Jacob M Van Laar, Professor UMC Utrecht

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03368235     History of Changes
Other Study ID Numbers: D6470C00003
First Posted: December 11, 2017    Key Record Dates
Last Update Posted: June 20, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
rheumatoid arthritis, swollen joints, tender joints, autoimmunity

Additional relevant MeSH terms:
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Connective Tissue Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents