Study to Evaluate PL8177 in Subjects With Non Infectious Uveitis (NIU)

Non-infectious Uveitis Clinical Trial

Official title:

A Phase 2, Open-Label Randomized Study to Evaluate Multiple Dosing Regimens of Subcutaneous PL8177 Administration in Subjects With Non Infectious Uveitis (NIU)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04105452
• Other study ID #: PL-8177-104
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 31, 2019
• Est. completion date: September 30, 2020

Study information

• Verified date: September 2019
• Source: Palatin Technologies
• Contact: Robert Jordan
• Phone: 609.495.2231
• Email: rjordan[@]palatin.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a Phase 2, open-label, randomized, 4-arm, parallel group study in subjects with active non-infectious uveitis. Subjects will be randomized to receive either 0.1 mg or 1.0 mg of PL8177 SC injection as 2 single doses 48 hours apart (Group A) or as a single dose for 4 weeks (4 doses) (Group B). A total of 40 subjects are planned to be enrolled with 20 participating in each Group.

Description:

Subjects will be screened to assess their eligibility to enter the study during a 7-day period within 39 days (Days -39 to -32) prior to the administration PL8177. On Day 1, all subjects will be randomized to receive either 0.1 mg or 1.0 mg of PL8177 subcutaneous injection as 2 single doses 48 hours apart (Group A) or as single weekly doses for 4 weeks (total 4 doses) (Group B).

All doses will be administered in the morning at approximately the same time each day after an overnight fast of at least 8 hours. A standard meal/snack will be provided at approximately 1 hour after dose administration. Subcutaneous injections will be administered in the anterior abdomen, in alternating quadrants. Study drug will be administered in clinic on Days 1 and 3 (Group A) or weekly on Days 1, 8, 15, and 22 (Group B). The study treatment period for Group A will be 3 days, followed by a 12-week post-treatment follow-up period, and for Group B will be a total of 22 days (4 weeks), followed by an 8-week post treatment period. A follow-up phone call will be made to each subject 4 weeks after completion of the study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: September 30, 2020
• Est. primary completion date: May 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Age = 18 to = 75 years of age at screening.

2. Is currently diagnosed with active, non-infectious intermediate-, posterior-, or panuveitis (including chronic anterior uveitis)

3. Must 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:

1. Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion

2. = 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria)

3. = 2+ VH (National Eye Institute [NEI]/SUN criteria)

4. Has provided informed consent prior to initiation of any study specific activities/procedures.

5. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits.

6. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and body weight not less than 50 kg.

7. Women of childbearing potential must have a negative serum pregnancy test at Screening and Day -2.

8. Male and female subjects of childbearing potential must agree to use 2 highly effective forms of birth control during study participation and for 30 days after the last dose of study drug, unless the subject or his/her partner is surgically sterilized, the subject agrees to abstain from sexual intercourse, or the subject is post-menopausal.

1. Highly effective methods of birth control in this study include: intrauterine device, hormonal contraceptives (oral, patch, long acting injectable, implant), double-barrier method (condom or diaphragm with spermicide).

2. Postmenopausal is defined as lack of menses for =6 months prior to screening, confirmed by serum follicle stimulating hormone (FSH) >25 mIU/mL at screening.

9. Subjects taking prescription medication for comorbidities (eg, hypothyroidism, hypertension) must be on a stable dose for 3 months prior to study start and maintain dose throughout study at discretion of investigator.

Exclusion Criteria:

• Diagnosis and main criteria for inclusion:

Inclusion Criteria

Subjects must satisfy all of the following criteria at the screening visit unless otherwise stated:

1. Age = 18 to = 75 years of age at screening.

2. Is currently diagnosed with active, non-infectious intermediate-, posterior-, or panuveitis (including chronic anterior uveitis)

3. Must 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:

1. Active, inflammatory, chorioretinal and/or inflammatory retinal vascular lesion

2. = 2+ anterior chamber cells (Standardization of Uveitis Nomenclature [SUN] criteria)

3. = 2+ VH (National Eye Institute [NEI]/SUN criteria)

4. Has provided informed consent prior to initiation of any study specific activities/procedures.

5. Understands and is willing and able to comply with study requirements, including the schedule of follow-up visits.

6. Body mass index (BMI) between 18 and 30 kg/m2, inclusive, and body weight not less than 50 kg.

7. Women of childbearing potential must have a negative serum pregnancy test at Screening and Day -2.

8. Male and female subjects of childbearing potential must agree to use 2 highly effective forms of birth control during study participation and for 30 days after the last dose of study drug, unless the subject or his/her partner is surgically sterilized, the subject agrees to abstain from sexual intercourse, or the subject is post-menopausal.

1. Highly effective methods of birth control in this study include: intrauterine device, hormonal contraceptives (oral, patch, long acting injectable, implant), double-barrier method (condom or diaphragm with spermicide).

2. Postmenopausal is defined as lack of menses for =6 months prior to screening, confirmed by serum follicle stimulating hormone (FSH) >25 mIU/mL at screening.

9. Subjects taking prescription medication for comorbidities (eg, hypothyroidism, hypertension) must be on a stable dose for 3 months prior to study start and maintain dose throughout study at discretion of investigator.

Exclusion Criteria

Subjects will be excluded from the study if they meet any of the following criteria at the screening visit unless otherwise stated:

1. Known sensitivity to fluorescein.

2. Subjects who are unwilling or unable to taper off systemic immunosuppressive therapy with corticosteroids, including prednisone, prior to receiving study drug.

3. Subjects with bilateral NIU, who in the opinion of the Investigator, have NIU in the fellow eye which cannot be controlled with standard local therapy(ies) alone.

4. Subjects with bilateral NIU who are receiving systemic immunomodulator therapy (eg, immunosuppressants, such as methotrexate, cyclosporine, cyclophosphamide, chlorambucil, mycophenolate mofetil, tacrolimus, or azathioprine; and biologics, such as infliximab, adalimumab, etc) other than prednisone or other corticosteroids for the treatment of NIU, AND who, in the opinion of the Investigator, have NIU in the fellow eye which cannot be controlled with standard local therapies

5. Subjects will be excluded if any of the following conditions are met in the study eye:

1. Diabetic retinopathy: proliferative diabetic retinopathy (PDR) or non-proliferative diabetic retinopathy (NPDR) that compromise the vision.

2. Age-related macular degeneration;

3. Myopic degeneration with active subfoveal choroidal neovascularization.

4. Advanced glaucoma status post trabeculectomy or tube/valve placement

5. Intraocular surgery, or panretinal or macular laser photocoagulation within 90 days prior to Day -2 in the study eye;

6. Capsulotomy within 30 days prior to Day -2 in the study eye;

7. History of vitreoretinal surgery or scleral buckling

8. Any ocular surgery (including cataract extraction or capsulotomy) of the study eye anticipated during the study

9. Any of the following treatments within 90 days prior to Day 1 or anticipated use of any of the following treatments to the study eye:

• Intravitreal injections (including but not limited to steroids or anti-vascular endothelial growth factors);

• Posterior subtenon's steroids

10. IOP =25 mm Hg in the study eye (glaucoma patients maintained on no more than 2 topical medications with IOP <25 mmHg are allowed to participate)

11. Inadequate pupillary dilation in the study eye

12. Media opacity that would limit clinical visualization, including fundus and OCT images.

13. Presence of any form of ocular malignancy in the study eye, including choroidal melanoma

14. History of herpetic infection in the study eye or adnexa

15. Aphakia, whether congenital or surgical

16. Vitreous hemorrhage

17. Subjects with visually significant vitreomacular traction or epiretinal membrane evident biomicroscopically or on OCT that is thought to affect central vision

18. Subjects with any other disease that might compromise visual acuity or require medical or surgical intervention during the study period, or could confound interpretation of the results (including retinal vascular occlusion, retinal detachment, macular hole or choroidal neovascularization of any cause)

6. Subjects will be excluded if any of the following conditions are met in either eye:

1. Presence of known active or inactive toxoplasmosis in either eye

2. Ocular or periocular infection in either eye

7. Subjects who have only one functional eye, even if the eye met all other study requirements, or who have an ocular condition on the fellow eye with a poorer prognosis than the study eye.

8. History of symptoms of demyelinating disease.

9. Participation in other investigational drug or device clinical trials within 30 days or 5 half lives, whichever is longer, prior to screening.

10. Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization

11. Presence of clinically significant laboratory abnormalities at screening that in the opinion of the Investigator would exclude the subject from the study.

12. History of cancer within the 5 years prior to screening including solid tumors and hematological malignancies (exception: no approval needed for basal cell and in situ squamous cell carcinomas of the skin that have been adequately treated with no re occurrence for at least 1 year prior to screening).

13. History of one or more clinically relevant neurologic, psychologic, ophthalmologic, pulmonary, cardiovascular, gastrointestinal, hepatic, renal, endocrine, or other major systemic disease of moderate (or worse) severity, making implementation of the protocol or interpretation of the study difficult. Examples of (but not limited to) conditions to be excluded, are the following:

1. Uncontrolled hypertension, with systolic =150 mm Hg, diastolic =90 mm Hg.

2. Uncontrolled hyperlipidemia (even if therapy is ongoing, LDL>160mg/dl or triglycerides >500mg/dL).

3. Uncontrolled hyperthyroidism or hypothyroidism.

4. Impaired hepatic function (AST or ALT values >2.0 times the upper limit of the reference range and/or serum bilirubin 1.5 times the upper limit of the reference range at the screening visit).

5. Cardiac or pulmonary disease, such as unstable angina or myocardial infarction within the past 12 months, congestive heart failure (CHF) Grade 2, 3, or 4 according to New York Heart Association criteria, valvular heart disease, cardiac arrhythmia requiring treatment, pulmonary hypertension, or chronic pulmonary disease requiring oxygen.

6. Stroke or transient ischemic attack (TIA) in the 12 months before screening.

7. Major depressive illness in the last 3 years; any history of severe psychiatric illness (eg, schizophrenia).

8. Multiple sclerosis or any other demyelinating disease.

14. Any of the following laboratory abnormalities:

1. Liver function tests >1.5 x the upper limit of normal (ULN) or direct bilirubin >1.5 x ULN.

2. Hemoglobin <8.5 g/dl (international system units [SI]: <85 g/L).

3. Neutrophils <1500/mm3(SI: < 1.5 x 109/L).

4. White blood cell (WBC) count <3,000/mm3 (SI: < 3.0 x 109/L).

5. Platelets <80,000 mm3 (SI: 80 x 109/L).

6. International normalized ratio (INR) >1.5.

7. Serum creatinine >1.5 x the ULN.

8. Hemoglobin A1C >6.5%.

15. Has a current bacterial, parasitic, fungal, viral, or mycobacterial infection, or any major episode of infection requiring hospitalization or treatment with intravenous antibiotics within 4 weeks prior to the screening visit and at any time during the screening period.

16. Serological evidence of human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C (HCVAb) at screening.

17. History of tuberculosis (TB) or Listeria infection, or known exposure to another person with active TB disease within 12 weeks of screening; or history of past or current infection with different opportunistic infections.

18. Clinically significant findings on 12-lead ECG such as, but not limited to, 2nd or 3rd AV block, prolongation of QRS complex over 120 msec, or QTcF interval =450 msec.

19. Any other laboratory abnormality, which, in the opinion of the investigator, poses a safety risk, will prevent the subject from completing the study, will interfere with the interpretation of the study results, or might cause the study to be detrimental to the subject.

20. Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed during the study and for an additional 30 days after study completion.

21. Females of child-bearing potential with a positive pregnancy test (assessed by a serum pregnancy test at screening and baseline).

22. Subject has known sensitivity to any of the products or components to be administered during dosing.

23. Has previously received PL-8177

24. Subjects who, in the opinion of the investigator, present with a condition that would compromise their safety or that would make study completion unlikely.

25. Has a history (within the past 12 months before screening) of drug abuse (defined as any illicit drug use), or a positive test for drugs of abuse at screening or Day -2.

26. Has a history of alcohol abuse (defined as alcohol consumption exceeding 14 units per week), or fails a breathalyzer test at Day 1.

27. Subjects who are heavy smokers. Light smokers (=10 cigarettes/day) are permitted to enroll into the study. A cotinine test will be performed at screening and Day -2.

28. Has donated blood or had an acute loss of blood (>500 mL) during the 3 months before study drug administration, or intends to donate blood or blood products within 30 days after the completion of the study.

29. Has had an acute, clinically significant illness within 30 days prior to Day 1, or has had a recent febrile illness with an abnormal body temperature for at least 72 hours before dosing on Day 1.

30. Has been on a significantly abnormal diet, in the opinion of the investigator, during the 4 weeks prior to the first dose of study medication.

31. Is an immediate family member of the Investigator, or an employee of the study center with direct involvement in the proposed study or other studies under the direction of the investigator or study center, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress.

Related Conditions & MeSH terms

• Non-infectious Uveitis
• Uveitis

Intervention

Drug:
• PL8177
PL8177 will be given at both 0.1 and 1.0mg across Groups A and B either 2 single doses 48 hours a part (Group A) or weekly doses (Group B).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Palatin Technologies

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change from baseline of Best Corrected Visual Acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study chart (ETDRS)		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Primary	Mean change from baseline in vitreous haze using the Standardization of Uveitis Nomenclature (SUN) scale		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Primary	Mean change from baseline in macular thickness as measured by Optical Coherence Tomography (OCT)		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	The proportion of subjects achieving a = 1 and = 2 step improvement or resolution of vitreous haze (VH) on SUN scale after therapy or at time of rescue		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in aqueous flare as measured by slit-lamp anterior segment assessment		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in degree of inflammation		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in leakage of disc		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in leakage of macula		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in leakage of vasculature		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in leakage of chorioretinal lesions		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in graded vitreous cells after therapy or at time of rescue		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Change from baseline in VFQ-25 (visual function questionnaire) Composite Score		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)
Secondary	Mean change from baseline in ocular pain		Assessed within the treatment period of 48 hours (Group A) and 4 weeks (Group B)