Clinical trial NCT03656692
Conditions: Uveitis, Posterior Uveitis, Intermediate Panuveitis
Sponsor: Mallinckrodt
Start date: 2018-10-05; Completion date: 2020-07-14
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The main reason for this study is to see if Acthar Gel can reduce inflammation in the uvea.

Also, safety information when using it for this purpose will be collected.

Detailed description:

Arms: arm 1: Participants received Acthar 1 mL (80 units \[U\]) subcutaneously (SC) 2 times per week for 36 weeks followed by a taper to Acthar 1 mL (80 U) SC once a week for 2 weeks, then 0.5 mL (40 U) SC once a week for 2 weeks.
Interventions: intervention 1: Acthar Gel
Intervention descriptions: intervention 1: Acthar gel for subcutaneous injection 80 units per mL (40 units per 0.5 mL)

Protocol documents:
Prot_SAP_000.pdf: 
CONFIDENTIAL AND PROPRIETARY 
CLINICAL STUDY PROTOCOL 
A Multicenter, Open Label Pilot Study to Explore the Efficacy and Safety of 
Acthar® in Subjects With Severe Noninfectious Intermediate Uveitis, 
Posterior Uveitis, or Panuveitis 
Protocol Number: MNK61074105 
Date of Amendment 3: 
18 September 2019 
Date of Amendment 2: 
15 April 2019 
Date of Amendment 1: 
26 July 2018 
Date of Original Protocol: 
05 June 2018 
Mallinckrodt ARD LLC 
1425 U.S. Route 206 
Bedminster, NJ 07921 
United States of America 
NCT03656692


Acthar® (Repository Corticotropin Injection) 
 
Protocol MNK61074105 Amendment 3 
Page 17 of 70 
 
 
CONFIDENTIAL AND PROPRIETARY 
 
 
 
6. 
SYNOPSIS  
Study Title: A Multicenter, Open Label Pilot Study to Explore the Efficacy and Safety of Acthar® in Subjects 
With Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis 
Protocol MNK61074105 Type: Phase 4  
Condition/Disease:  
Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU) 
Approximate Number of 
Subjects: 30 
Approximate Duration of Subject Participation: 48 weeks 
Approximate Study 
Centers: 10 in the US 
Approximate Duration of Study: 18 months 
 
Design:  
This is a multicenter, multiple dose, open label study to examine the effects of Acthar in adult subjects 
with severe NIPPU. Approximately 30 subjects will be enrolled. Subjects with current severe NIPPU 
who meet entry criteria will be treated with Acthar 1 mL (80 units [U]) subcutaneously (SC) 2x/week 
for 36 weeks. Followed by a taper to Acthar 1 mL (80 U) SC once a week for 2 weeks, then 0.5 mL 
(40 U) SC once a week for 2 weeks.  
All subjects will have a follow-up contact 28 (± 14) days after their last dose of study drug. 
Objectives: 
Primary Objective 
Endpoints 
To explore the efficacy 
of Acthar in subjects 
with severe NIPPU in 
reducing aqueous and 
vitreous indicators of 
inflammation. 
Proportion of subjects with a 2 or more step reduction from baseline (or 
achievement of Grade 0) in vitreous haze at 36 weeks. 
Proportion of subjects with a 2 or more step reduction from baseline (or 
achievement of Grade 0) in aqueous flare at 36 weeks. 
Proportion of subjects with a 2 or more step reduction from baseline (or 
achievement of Grade 0) in aqueous cells at 36 weeks. 
Secondary Objective 
Secondary Endpoints 
To further explore the 
safety and tolerability of 
Acthar in subjects with 
severe NIPPU. 
Incidence and severity of ocular adverse events (AEs). 
Incidence and severity of other AEs. 
New or worsening cataracts. 
Mean change in intra-ocular pressure (IOP). 
Exploratory Objectives Exploratory Endpoints 
 
 
 
 
 
 
 
 
 
 


Acthar® (Repository Corticotropin Injection) 
 
Protocol MNK61074105 Amendment 3 
Page 18 of 70 
 
 
CONFIDENTIAL AND PROPRIETARY 
 
 
 
Study Title: A Multicenter, Open Label Pilot Study to Explore the Efficacy and Safety of Acthar® in Subjects 
With Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis 
Protocol MNK61074105 Type: Phase 4  
Condition/Disease:  
Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Entry Criteria: 
Male or nonpregnant, nonlactating female subjects 18 years of age or older with who have been 
diagnosed with current severe NIPPU and have active disease at the Baseline Visit as defined by the 
presence of at least 1 of the following parameters in at least one eye despite at least 2 weeks of 
maintenance therapy with oral prednisone (or oral corticosteroid equivalent): 
Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion. 
≥ 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria). 
≥ 1.5+ vitreous haze. 
Subjects must be willing to taper their current doses of corticosteroid and immunomodulatory therapy to 
the minimum effective dose during the study. 
Subjects may be under treatment with any immunosuppressants, immunomodulators, or biologic agents 
for a comorbid condition as long as they are on a stable dose for 2 weeks prior to screening. Subjects 
with proliferative or severe nonproliferative diabetic retinopathy, clinically significant macular edema 
due to diabetic retinopathy, neovascular/wet age-related macular degeneration, abnormality of vitreo-
retinal interface with the potential for macular structural damage independent of the inflammatory 
process or severe vitreous haze that precludes visualization of the fundus at the Baseline Visit will be 
excluded. 
Subjects with Type 1 or Type 2 diabetes mellitus, tuberculosis, history of hepatitis, peptic ulcer, active 
infection, or any contraindication for Acthar will be excluded.  


Acthar® (Repository Corticotropin Injection) 
 
Protocol MNK61074105 Amendment 3 
Page 19 of 70 
 
 
CONFIDENTIAL AND PROPRIETARY 
 
 
 
Study Title: A Multicenter, Open Label Pilot Study to Explore the Efficacy and Safety of Acthar® in Subjects 
With Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis 
Protocol MNK61074105 Type: Phase 4  
Condition/Disease:  
Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU) 
Concomitant Medications and Treatments:  
Subjects are not permitted to receive live or live-attenuated vaccines; topical, ophthalmic, or intra-ocular 
corticosteroids for a concomitant condition during the study. 
The use of corticosteroid therapy and immunomodulators for uveitis are permitted provided the subject 
has been on a stable dose for at least 2 weeks prior to the Screening Visit and is willing to taper to the 
lowest effective dose during the study.  
Subjects with stable comorbid conditions that are commonly associated with uveitis may continue with 
their current therapies that were stable for 2 weeks prior to screening. 
All medications and nondrug therapies (eg, blood transfusions, oxygen supplementation) taken from 
30 days prior to the Screening Visit and throughout the study will be recorded.  
Study Drug and Treatment Administration:  
Acthar is a sterile preparation of adrenocorticotropic hormone (ACTH) analogue formulated in a gel for 
repository administration. Acthar is supplied as 5 mL multidose vials. Acthar vials contain 80 U of 
ACTH per mL.  
The following treatments will be administered to all subjects: 
Acthar 1 mL (80 U) SC doses 2x/week for 36 weeks, followed by a taper to 1 mL (80 U) SC doses once 
per week for 2 weeks and then 0.5 mL (40 U) SC once a week for an additional 2 weeks. 
Efficacy Evaluations: 
The following efficacy assessments will be evaluated: Ophthalmic Examination, Spectral domain optical 
coherence tomography (SD-OCT), Fundus Photography, Fluorescein Angiography, and T-cell numbers. 
Safety Evaluations:  
The following safety assessments will be evaluated: adverse events, ophthalmology examinations, 
physical examination, clinical laboratory test results (Chemistry, Hematology, lipid profile and 
Urinalysis), glycosylated hemoglobin (HbA1c), pregnancy testing, and vital signs. 
Quality of Life/ Health Outcome Evaluations: 
The following quality of life (QOL)/health outcome assessments will be evaluated: National Eye 
Institute Visual Function Questionaire-25. 
Statistical Methods: 
Analysis Populations 
The Modified Intent-to-Treat (mITT) Population will include all subjects who receive at least 1 dose of 
study drug and who contribute any postbaseline efficacy data to the study.  
The Per-Protocol Population will include the subset of the mITT population who complete the study as 
per protocol, have no missing primary endpoint data, and do not have any major protocol deviations.  
The Safety Population will include all subjects who receive 1 or more doses of study drug. 


Acthar® (Repository Corticotropin Injection) 
 
Protocol MNK61074105 Amendment 3 
Page 20 of 70 
 
 
CONFIDENTIAL AND PROPRIETARY 
 
 
 
Study Title: A Multicenter, Open Label Pilot Study to Explore the Efficacy and Safety of Acthar® in Subjects 
With Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis 
Protocol MNK61074105 Type: Phase 4  
Condition/Disease:  
Severe Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis (NIPPU) 
Sample Size A total of 30 subjects will be enrolled in this study. No formal sample size calculations 
were performed. The sample size was determined empirically. 
Efficacy Analysis  
All efficacy analyses will be performed on the mITT population. Selected analyses will be performed on 
the Per-Protocol population. 
The primary efficacy endpoints will include: 
Proportion of subjects with a 2 or more step reduction from baseline (or achievement of Grade 0) in 
vitreous haze at 36 weeks. 
Proportion of subjects with a 2 or more step reduction from baseline (or achievement of Grade 0) in 
aqueous flare at 36 weeks. 
Proportion of subjects with a 2 or more step reduction from baseline (or achievement of Grade 0) in 
aqueous cells at 36 weeks. 
The primary efficacy endpoints will be analyzed on both mITT population and the Per-Protocol 
population. The endpoints will be summarized with frequency tables and evaluated with one-sample 
binomial test. The nominal p-values along with the 95% confidence intervals (CI) will be provided. 
For subjects with both eyes affected, the change from baseline will be determined based on the eye with 
the worst severity at baseline. If both eyes have the same severity at baseline, the right eye will be used 
to determine change from baseline. The same principle will be applied to efficacy endpoints when 
change from baseline is evaluated. 
Other efficacy endpoints will be summarized with descriptive statistics and the changes from baseline 
will be evaluated with test statistics and/or 95% CI as appropriate. 
Safety Analysis 
Treatment-emergent adverse events and serious adverse events will be summarized using the 
appropriate version of MedDRA by preferred term within system organ class. 
Other safety data will be listed and summarized descriptively or graphically, as appropriate.