ASIS for Enbrel in Plaque Psoriasis (ASISinPP)

ASIS

Status and phase: Unknown; Phase 2; Phase 1

Conditions: Plaque Psoriasis.

Treatments: Drug: Adverse Reactions of Enbrel subdermally at Week 36; Drug: Efficacy of Enbrel subcutaneously at Week 36; Drug: PASI 75 n(%) subdermally at Week 12; Drug: PASI 75 n(%) subcutaneously at Week 12; Drug: Efficacy of Enbrel subcutaneously at Week 24; Drug: Efficacy of Enbrel subdermally at Week 36; Drug: Efficacy of Enbrel subdermally at Week 12; Drug: PASI 75 n(%) subcutaneously at Week 24; Drug: PASI 75 n(%) subdermally at Week 36; Drug: Adverse Reactions of Enbrel subcutaneously; Drug: Gadolinium; Drug: PASI 75 n(%) subcutaneously at Week 36; Drug: Efficacy of Enbrel subcutaneously at Week 12; Drug: Efficacy of Enbrel subdermally at Week 24; Drug: PASI 75 n(%) subdermally at Week 24

Study type: Interventional

Funder types: Industry

Identifiers

NCT02112097

NCTAR066986

R44AR066986 (Other Grant/Funding Number)

Details and patient eligibility

About

AUTOMATIC SUBDERMAL INJECTOR SYSTEM (ASIS) Corporation has developed and patented the only automatic injection system for delivery of injectable products to the optimum spot, just outside of the fascia, which exists subdermally (between the skin and muscle) or interfascial (between the deeper muscles). ASIS device creates that bloodless space, enhancing Enbrel's efficacy and preventing unnecessary distant spread and adverse reactions. This space remains bloodless as long as the skin is lifted up or filled with an injectable product. Although ASIS device was initially designed to best administer BOTOX for such muscular conditions as Upper limb Spasticity, Cervical Dystonia, Chronic Migraine, Strabismus, Blepharospasm, and Primary Axillary Hyperhidrosis, the technology will also benefit other injectable products, including: GAMMAGARD for Primary Immunodeficiency (PI) and Insulin for Diabetics, etc.

Full description

Over 6 months, Aim 1 will demonstrate that ASIS device consistently delivers an injectable product (e.g. Gadolinium) into that subdermal bloodless space. MRI is the most simple and logical imaging choice, preferred because with ultrasound, air is injected, which will dissipate too quickly out of bloodless space to allow measurements. Since there isn't a way to measure the level of Gadolinium within that subdermal bloodless space, at least the Prolongation of Gadolinium may be approximated by its greater or longer Persistent % on MRI. Also, since we can't assume that bloodless space for patients with a particular disease will behave the same way as normal patients or patients with different diseases, this approximation only works if the variables are minimized to the same particular skin affected by Plaque Psoriasis. Case in point, patients with Plaque Psoriasis tend to have thicker skin, so expectantly will have prolonged Gadolinium subcutaneously Persistent %, which may be very different from the other diseases and certainly from the skin of normal patients, while the Gadolinium subdermally Persistent % should remain the same. Therefore, the Relative Prolongation Ability Score or total Persistent % subdermally over total Persistent % subcutaneously, will be different and very specific for the particular skin affected by Plaque Psoriasis. However, they are valuable indicators that will help us modify the Enbrel dosage and duration to inject into that "unknown" subdermal space for Aim 2, from the "known" typical Enbrel dosage and duration for Plaque Psoriasis patients. For example, if Aim 1 found the Relative Prolongation Ability Score for the Plaque Psoriasis skin to be (2.00), then the typical subcutaneously Enbrel 50mg every 3 days, should be 25mg every 6 days subdermally.

Over 12 months, Aim 2 will again demonstrate the advantages of ASIS device injecting subdermally versus subcutaneously, but using Enbrel instead of Gadolinium on the particular skin affected by Plaque Psoriasis. Once we have shown ASIS device's consistent performance in Aim 1, then we may assume will deliver another product (Enbrel) into that bloodless space without the need to measure Enbrel's existent in that bloodless space. Using Enbrel instead of Gadolinium, we'll demonstrate the advantages of injecting subdermally over intramuscularly for the same affected skin sites in the same 60 adult subjects.

Enrollment: 60 estimated patients

Sex: All

Ages: 21 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Inclusion Criteria in general and for Gadolinium:
• Main Criteria for Inclusion: Eligible Ages: 12 Years to 65
• Genders Eligible for Study: Both
• Accepts Healthy Volunteers: Yes
• Must be outpatient, male or female, of any race, between 18 and 65 years of age.
• Must be able to understand the requirements of the study including maintaining a diary, and sign informed consent.
• Must be in good general health as determined by investigator.
• If female of childbearing potential, must have negative pregnancy test result at screening visit and practice reliable method of contraception
• Inclusion Criteria for Plaque Psoriasis in particular:
• Must have chronic moderate to severe plaque psoriasis and be candidates for systemic therapy or phototherapy.
• Must have psoriasis involving at least 10% of body surface and a minimum PASI score of 10.
• Patients are limited to low-moderate-strength topical corticosteroids in axillary, groin, and scalp regions.

Exclusion criteria

• Exclusion Criteria for Plaque Psoriasis in particular:
• Patients with guttate, erythrodermic, or pustular psoriasis and patients with severe infections within 4 weeks of screening are excluded from study.
• No concomitant major anti-psoriatic therapies are allowed during the study.
• Has chronic or recurrent infection, has been exposed to tuberculosis, has resided or traveled in areas of endemic tuberculosis or endemic mycoses, such as histoplasmosis, coccidioidomycosis, or blastomycosis; or has underlying conditions that may predispose them to infection such as advanced or poorly controlled diabetes

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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60 participants in 13 patient groups

For Left Upper Arm

Experimental group

Description:

For Left Upper Arm Total Persistent % subdermally, For Left Upper Arm Total Persistent % subcutaneously, and For Left Upper Arm Relative Prolongation Ability Score. Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9cc normal saline subcutaneously for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

For Right Upper Arm

Experimental group

Description:

For Right Upper Arm Total Persistent % subdermally, For Left Upper Arm Total Persistent % subcutaneously, and For Left Upper Arm Relative Prolongation Ability Score. Gadolinium Magnevist® (gadopentetate dimeglumine) .1cc/ diluted with .9cc normal saline subcutaneously for 30 patients, and subdermally with ASIS Device for 30 patients.

Treatment:

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

Drug: Gadolinium

sPGA 50 n(%)

Experimental group

Description:

sPGA 50 n(%) as Efficacy of Enbrel subcutaneously at Week 12, Efficacy of Enbrel subcutaneously at Week 24, and Efficacy of Enbrel subcutaneously at Week 36 vs. Efficacy of Enbrel subdermally at Week 12, Efficacy of Enbrel subdermally at Week 24, and Efficacy of Enbrel subdermally at Week 36. sPGA 50 n(%) "clear" or "minimal" is the % of patients who achieve a score of "clear" or "minimal" by the Static Physician Global Assessment (sPGA) and % of patients with a reduction of PASI of at least 50% from baseline.

Treatment:

Drug: Efficacy of Enbrel subcutaneously at Week 24

Drug: Efficacy of Enbrel subcutaneously at Week 12

Drug: Efficacy of Enbrel subcutaneously at Week 36

Drug: Efficacy of Enbrel subdermally at Week 36

Drug: Efficacy of Enbrel subdermally at Week 24

Drug: Efficacy of Enbrel subdermally at Week 12

PASI 75 n(%)

Experimental group

Description:

PASI 75 n(%) Response to treatment defined as the proportion of patients who achieved a reduction in score of at least 75% from baseline by the PASI, as PASI 75 n(%) subcutaneously at Week 12, PASI 75 n(%) subcutaneously at Week 24, and PASI 75 n(%) subcutaneously at Week 36 vs. PASI 75 n(%) subdermally at Week 12, PASI 75 n(%) subdermally at Week 24, and PASI 75 n(%) subdermally at Week 36.

Treatment:

Drug: PASI 75 n(%) subdermally at Week 24

Drug: PASI 75 n(%) subcutaneously at Week 36

Drug: PASI 75 n(%) subdermally at Week 36

Drug: PASI 75 n(%) subcutaneously at Week 24

Drug: PASI 75 n(%) subcutaneously at Week 12

Drug: PASI 75 n(%) subdermally at Week 12

Adverse Injection site reactions

Experimental group

Description:

Injection site reactions as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions with Heart failure

Experimental group

Description:

Heart failure as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions Allergic Reactions

Experimental group

Description:

Allergic Reactions as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions Blood/low blood counts

Experimental group

Description:

Blood problems/low blood counts as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions with Nervous system

Experimental group

Description:

Nervous system problems, such as multiple sclerosis, seizures, or inflammation of the nerves of the eyes, as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions with Infections

Experimental group

Description:

Infections (upper respiratory infection, pyelonephritis, bronchitis, septic osteomyelitis, wound infection, pneumonia, foot abscess, leg ulcer), as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions with Malignancies

Experimental group

Description:

Malignancies (lymphoma, basal \& squamous skin cancer, non-cutaneous solid tumor, \& Wegener's granulomatosis), as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions with Immunogenicity

Experimental group

Description:

Immunogenicity as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36

Adverse Reactions with Autoantibodies

Experimental group

Description:

Autoantibodies, Lupus-like syndrome, autoimmune hepatitis, as Adverse Reactions of Enbrel subcutaneously vs. Adverse Reactions of Enbrel subdermally at Week 36.

Treatment:

Drug: Adverse Reactions of Enbrel subcutaneously

Drug: Adverse Reactions of Enbrel subdermally at Week 36