A Phase IIa, Multi-Centre, Randomised, Double-Blind, Comparator Controlled, Repeated-Dose Study of 2 Dose Levels of AK106 001616 in Patients with Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 11 September 2012
• Main ID: EUCTR2010-021558-21-HU
• Date of registration: 07/10/2010
• Prospective Registration: Yes
• Primary sponsor: Asahi Kasei Pharma Corporation
• Public title: A Phase IIa, Multi-Centre, Randomised, Double-Blind, Comparator Controlled, Repeated-Dose Study of 2 Dose Levels of AK106 001616 in Patients with Rheumatoid Arthritis
• Scientific title: A Phase IIa, Multi-Centre, Randomised, Double-Blind, Comparator Controlled, Repeated-Dose Study of 2 Dose Levels of AK106 001616 in Patients with Rheumatoid Arthritis
• Date of first enrolment: 08/02/2011
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-021558-21
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Czech Republic, Germany, Hungary, Slovakia, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Has been diagnosed with adult-onset RA (as defined by the 1987 American College of Rheumatology [ACR] classification criteria) for at least 3 months.

2. Has a Functional Capacity Classification of I-III (as described in Appendix E of the protocol).

3. Has been stable on oral MTX therapy (5 to 25 mg administered as a single weekly dose) for at least 12 weeks.

4. Has RA activity at screening and at baseline (Day 1, pre-morning dose), defined as a 28-joint disease activity score (DAS28) of =3.2 and a change in DAS28 score from screening to baseline that is >0 and =1.2 (baseline minus screening).

5. Between 18 and 65 years of age inclusive.

6. Is able to give voluntary written informed consent to participate in this trial.

7. If female and of childbearing potential, the patient must confirm she is using adequate contraception since last her menses, and have a negative result on the urine pregnancy test taken before the administration of the study drug. She must be willing to consent to the continued use of adequate contraception during the study and for 3 months after the study conclusion. Adequate contraception is defined as the use of 2 acceptable methods of birth control (ie, a hormonal contraceptive, intra uterine device, diaphragm with spermicide, and condom with spermicide). A condom alone is not considered an acceptable method of birth control.

8. If male with a sexual partner who is a woman of childbearing potential, the patient must confirm that he and his sexual partner agree to use 2 acceptable methods of birth control (ie, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, and condom with spermicide) during the study and for 3 months after the study conclusion.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
(To meet 5000 character limit, only most important listed in full)

1. Has been diagnosed with a secondary, non-inflammatory type of arthritis (eg, osteoarthritis or fibromyalgia) that might interfere with the evaluation of the effect of study medication on RA symptoms.

2. Is pregnant or is breastfeeding.

3. Has taken any NSAID (including aspirin) within 5 times the half-life of the NSAID or a minimum of 2 days before the start of the baseline visit (defined as Day -1 for VCE assessment subgroup and defined as Day 1 for all other patients) or any analgesic within 24 hours before the baseline visit. Patients taking =150 mg aspirin per day for non-arthritis reasons for at least 30 days before the first dose of study medication will be permitted to enter the study and will be allowed to continue their aspirin regimen for the duration of the study.

4. Has taken any anti-ulcer drugs (ie, H2 blockers, proton pump inhibitors, etc) during the NSAID washout period.

5. Has been treated with:
- Anti-tumour necrosis factor (TNF) drugs or other biologicals (except rituximab), eg, anakinra, abatacept, in the past 3 months.
- Rituximab in the past 6 months.

6. Has begun taking DMARDs or immunosuppressants other than biologicals (eg, gold salts [including oral gold], sulfasalazine, MTX, azathioprine, antimalarials, penicillamine, combination therapies used in RA treatment, leflunomide) and other physical/surgical treatments for RA or has changed the dosing regimen of any of these medications within 12 weeks before receiving the first dose of study medication.

7. Has reduced MTX dose within 6 months before the first dose of study medication because of any side effect related to MTX administration.

8. Has begun taking oral corticosteroids or changed the dose regimen of oral corticosteroids within 4 weeks before receiving the first dose of study medication (doses of up to 10 mg prednisone or equivalent per day are allowed), or has received intramuscular, intra-articular or soft-tissue injections of corticosteroids within 8 weeks before receiving the first dose of study medication.

9. Has received any antineoplastic (other than MTX =25 mg/week or azathioprine as therapy for RA) during the 8 weeks preceding the first dose of study medication.

10. Has an active malignancy of any type or a history of malignancy (with the exception of patients who have been in remission for at least 5 years and patients who have a history of treated basal cell carcinoma or carcinoma in situ of the cervix).

11. (a) Has a history of 2 or more types of active peptic ulceration as below:
- GI bleeding
- Recurrent gastric ulcers
- Duodenal ulcers OR
(b) Has an oesophageal, gastric or duodenal ulcer within 30 days before the first dose of study medication; OR
(c) Has active GI disease that precludes NSAID therapy.

12. Has clinically significant chronic/acute hepatic or renal disorder or a significant coagulation defect.

13. Has 1 or more of the following:
- An abnormal screening laboratory test value that is considered by the investigator to be clinically significant
- A value that is >2 times the upper limit of normal (ULN) for AST or ALT at screening
- A value for serum creatinine >1.5 times the ULN at screening
- An absolute neutrophil count (ANC) <1800/mm3 (or WBC <3.5 x 109/L), haemoglobin <10 g/dL, or platelets <100 x 109/L at screening

14. Has a known hypersensitivity to paracetamol and/or NSAIDs.

15. Is taking a drug that is known to have an interaction with M

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis
MedDRA version: 9.1 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: AK106-001616
Product Code: AK106-001616
Pharmaceutical Form: Capsule, hard
CAS Number: 590416-75-4
Current Sponsor code: AK106-001616 (form B)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: Naprosyn 500 mg
Product Name: Naprosyn 500 mg
Pharmaceutical Form: Capsule*
INN or Proposed INN: naproxen
CAS Number: 22204-53-1
Current Sponsor code: naproxen
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 500-
Pharmaceutical form of the placebo: Capsule*
Route of administration of the placebo: Oral use

Product Name: AK106-001616
Product Code: AK106-001616
Pharmaceutical Form: Capsule, hard
CAS Number: 590416-75-4
Current Sponsor code: AK106-001616 (form B)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: - To investigate the clinically relevant improvement in anti-inflammatory/analgesic activity after multiple doses of AK106-001616 compared with naproxen in patients with RA.
- To compare the safety of AK106-001616 to that of naproxen in patients with RA.

Primary end point(s): Efficacy endpoints:
- Patient global assessment of arthritis (VAS)
- Patient assessment of arthritis pain (VAS)
- Physician global assessment of arthritis (VAS)
- Number of tender/painful joints (68 join count)
- Number of swollen joints (66 joint count)
- ACR20 responder index
- ACR50 responder index
- DAS28 score
- European League Against Rheumatism (EULAR) response criteria
- HAQ functional disability index
- Acute phase reactant (C-reactive protein)
- Erythrocyte sedimentation rate (ESR)
- Incidence of withdrawal due to lack of arthrtis efficacy

Safety endpoints:
- Adverse events
- Vital signs
- Clinical laboratory tests (clinical chemistry, haematology, serology, urinalysis)
- 12-lead Electrocardiogram (ECG)
- Physical exam
- Video capsule endoscopy (optional subpopulation)

Pharmacokinetic (PK) endpoints:
- AK106-001616 plasma concentration-time profiles will be evaluated in population PK analyses.

Pharmacodynamic (PD) endpoints:
- Urine efficacy PD biomarkers: LTE4/urine creatinine, PGE-M/urine creatinine
- Urine safety PD biomarkers: 2,3-dinor 6-keto PGF1a/urine creatinine, 6-keto PGF1a/urine creatinine, 11-dehydro TXB2/urine creatinine, 11-dehydro TXB2/urine 2,3-dinor 6-keto PGF1a ratio
- Serum PD biomarkers: matrix metalloproteinase 3 (MMP3), crosslinked N-telopeptide of type 1 collagen (NTX), interleukin-6 (IL-6), interleukin-10 (IL-10), TNF-alpha (TNFa)

Secondary Objective: - To compare the safety and efficacy of multiple, oral doses of AK106-001616 with that of naproxen in patients with RA using pharmacodynamic (PD) urinary biomarkers.
- To compare the effect of AK106-001616 on the gastrointestinal (GI) tract to that of naproxen in a subpopulation of the RA patients (based on optional Video Capsule Endoscopy [VCE] assessment).

Secondary ID(s)

AK106 II-02