Trial Outcomes & Findings for First-line Antimetabolites as Steroid-sparing Treatment Uveitis Pilot Trial (NCT NCT01232920)

NCT ID: NCT01232920

Last Updated: 2016-07-15

Results Overview

TREATMENT SUCCESS is defined as controlled ocular inflammation in both eyes with less than or equal to 10 mg/day of prednisone and/or 2 topical steroid drops/day sustained for 2 visits separated by at least 28 days (control of inflammation and prednisone dose must be achieved by 5-month visit and sustained until 6-month visit). Discontinuation of study medication at any time due to efficacy, tolerability, or safety may result in a declaration of TREATMENT FAILURE. Note that all patients will be classified as either a treatment success or failure.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 80 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2016-07-15

Participant Flow

Participant milestones

Measure	Methotrexate Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Overall Study STARTED	41	39
Overall Study COMPLETED	35	32
Overall Study NOT COMPLETED	6	7

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

First-line Antimetabolites as Steroid-sparing Treatment Uveitis Pilot Trial

Baseline characteristics by cohort

Measure	Methotrexate n=41 Participants Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=39 Participants Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.	Total n=80 Participants Total of all reporting groups
Age, Continuous	38.6 years STANDARD_DEVIATION 10.3 • n=5 Participants	40.5 years STANDARD_DEVIATION 14.2 • n=7 Participants	40.4 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	22 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	17 Participants n=7 Participants	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

TREATMENT SUCCESS is defined as controlled ocular inflammation in both eyes with less than or equal to 10 mg/day of prednisone and/or 2 topical steroid drops/day sustained for 2 visits separated by at least 28 days (control of inflammation and prednisone dose must be achieved by 5-month visit and sustained until 6-month visit).

Discontinuation of study medication at any time due to efficacy, tolerability, or safety may result in a declaration of TREATMENT FAILURE. Note that all patients will be classified as either a treatment success or failure.

Outcome measures

Measure	Methotrexate n=35 Participants Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=32 Participants Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Number of Participants Achieving Treatment Success	24 participants	15 participants

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Methotrexate n=35 Participants Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=32 Participants Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Time to Control of Inflammation	139 days Interval 62.5 to 142.0	124 days Interval 60.0 to 156.0

SECONDARY outcome

Timeframe: 6 months

Change in best spectacle-corrected visual acuity (BSCVA) from baseline. Analysis on eye level

Outcome measures

Measure	Methotrexate n=68 Eyes Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=56 Eyes Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Change in Best Spectacle-corrected Visual Acuity (BSCVA)	-0.26 LogMAR Standard Deviation 0.33	-0.19 LogMAR Standard Deviation 0.36

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Measure	Methotrexate n=68 Eyes Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=56 Eyes Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Number of Eyes With Resolution of Macular Edema Eyes with Macular Edema at Baseline	22 Eyes	13 Eyes
Number of Eyes With Resolution of Macular Edema Eyes with Resolved Macular Edema	17 Eyes	7 Eyes

Adverse Events

Methotrexate

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Mycophenolate Mofetil

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Methotrexate n=41 participants at risk Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=39 participants at risk Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Skin and subcutaneous tissue disorders Hospitalization	0.00% 0/41	2.6% 1/39 • Number of events 1

Other adverse events

Measure	Methotrexate n=41 participants at risk Methotrexate: All methotrexate doses will be taken orally once per week in a divided dose (half in the morning, half in the evening), and should be taken with food. For the first two weeks, a loading dose of 15 mg/week orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 25 mg/week until the end of follow-up or until treatment failure due to intolerability, adverse events, or of lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 20 mg per week while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 15 mg per week.	Mycophenolate Mofetil n=39 participants at risk Mycophenolate mofetil: Mycophenolate mofetil will be taken twice daily on an empty stomach. For the first two weeks, a loading dose of 500 mg/BID orally will be administered to assess tolerability. After two weeks, the dose will be ramped up to 1 g/BID until the end of follow-up or until treatment failure due to intolerability, adverse events, or lack of efficacy. If the study ophthalmologist decides to reduce the study treatment dose due to intolerability, the dose will be reduced to 750 mg/BID while maintaining masking. If side effects persist and the study ophthalmologist wishes to reduce the dose a second time, the dose will be reduced to 500 mg/BID.
Gastrointestinal disorders Nausea	14.6% 6/41	5.1% 2/39
Gastrointestinal disorders Diarrhea	9.8% 4/41	10.3% 4/39
Gastrointestinal disorders Vomiting	7.3% 3/41	5.1% 2/39
Infections and infestations Systemic infection	7.3% 3/41	10.3% 4/39
Eye disorders Cataract	12.2% 5/41	7.7% 3/39
Eye disorders Ocular hypertension	9.8% 4/41	5.1% 2/39
Eye disorders Glaucoma	4.9% 2/41	5.1% 2/39
General disorders Headache	19.5% 8/41	30.8% 12/39
Infections and infestations Fever for 12 hours	4.9% 2/41	23.1% 9/39

Additional Information

Nisha Acharya

Proctor Foundation, University of California San Francisco

Phone: 415-476-8131

Email: nisha.acharya@ucsf.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place