Clinical Application of Stem Cell Educator Therapy in Alopecia Areata

• ClinicalTrials.gov Identifier: NCT04011748
• Recruitment Status: Not yet recruiting
• First Posted: July 8, 2019
• Last Update Posted: June 30, 2021
• Sponsor: Throne Biotechnologies Inc.
• Collaborators: Yale University; Hackensack Meridian Health
• Information provided by (Responsible Party): Throne Biotechnologies Inc.

Study Description

Brief Summary:

Alopecia areata (AA) is a common autoimmune disease that results in loss of body hair in varying degrees. The condition is estimated to affect more than 6.5 million people in the United States alone (naaf.org), with a worldwide prevalence of 0.1% to 0.2% and calculated lifetime risk of 2%. AA is the most common form of the disease, in which areas of complete hair loss arise within normal hair-bearing skin. Other forms include alopecia totalis (AT), characterized by total loss of scalp hair, and alopecia universalis (AU), characterized by complete loss of body hair. AA and its variants can have devastating effects on patients' quality of life and social functioning. At present, curative therapy for AA does not exist. Therapeutic options are currently very limited, such as intralesional injections of glucocorticoids and induction of allergic contact dermatitis. These therapies are not effective for many patients and are generally impractical for patients with diffuse AA, AT or AU. Recently, Janus kinase (JAK) inhibitors were effective for the treatment of severe AA. However, for those patients who do respond, relapses are common after discontinuation of treatment, due to the existing of autoimmune memory T cells. Stem Cell Educator (SCE) therapy, which uses only autologous mononuclear cells that are externally exposed to cord blood stem cells, has previously been proven safe and effective in subjects for the improvement of type 1 diabetes (T1D), T2D and other autoimmune diseases such as alopecia areata. Minoxidil is the FDA approved drug for the treatment of androgenetic alopecia (AGA) in 1988. This trial will explore the therapeutic potential of Stem Cell Educator therapy for the treatment of AA in combined with oral minoxidil.

Condition or disease	Intervention/treatment	Phase
Alopecia Areata; Alopecia Totalis; Alopecia Universalis	Combination Product: Stem Cell Educator therapy combined with minoxidil	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: AA subjects will receive the treatment with Stem Cell Educator therapy in combined with oral minoxidil.
• Masking: Double (Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Treatment of Alopecia Areata With Stem Cell Educator Therapy and Oral Minoxidil
• Estimated Study Start Date: October 30, 2021
• Estimated Primary Completion Date: April 30, 2022
• Estimated Study Completion Date: June 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Haire regrowth by SCE; AA subjects will receive Stem Cell Educator therapy combined with oral minoxidil. Hair regrowth will be evaluated during one-year follow-up studies.	Combination Product: Stem Cell Educator therapy combined with minoxidil; AA subjects will be recruited and initially primed with oral minoxidil for 30 days, and followed by the treatment with SCE therapy.
Experimental: Minoxidil therapy; Control subjects will receive treatment with topical 5% minoxidil	Combination Product: Stem Cell Educator therapy combined with minoxidil; AA subjects will be recruited and initially primed with oral minoxidil for 30 days, and followed by the treatment with SCE therapy.

Outcome Measures

Primary Outcome Measures :

1. The percentage change in scalp hair growth. [ Time Frame: Hair regrowth will be evaluated at different time points post receiving Stem Cell Educator therapy in 1, 3, 6, 9, and 12 months. ]
   The primary endpoint was the percentage change in scalp hair growth, measured with the Severity of Alopecia Tool (SALT) score.

Secondary Outcome Measures :

1. Feasibility of SCE therapy combined with minoxidil [ Time Frame: 12 months ]
   The feasibility will be determined by the number of patients who were unable to complete SCE Therapy.
2. Preliminary efficacy of SCE therapy combined with minoxidil [ Time Frame: 12 months ]
   This will be determined by the duration of maintaining hair growth following SCE therapy.
3. Efficacy of modulation of autoimmune-related memory T-cell markers [ Time Frame: 12 months ]
   Measurements of immune markers' changes will be preformed by flow cytometry such as CD8+CD45RO+CCR7- effector memory T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12 month post the SCE therapy.
4. Feasibility of SCE therapy combined with minoxidil [ Time Frame: 12 month ]
   The number of patients who are lost to follow-up prior to the 12-month follow-up visit.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Adult patients ( 18 years)
2. Must have a clinical diagnosis of AA, at least 50% hair loss involving the scalp
3. For cases in which there is 80% or more scalp hair loss, the duration of the severity of hair loss must be 10 years or less
4. Stable or worsening hair loss for at least 6 months without evidence of hair regrowth
5. Patients must not have received any treatments known to affect AA within 2 months of screening
6. Patients must agree that they are not permitted to use any other treatment besides oral minoxidil known to affect AA during a period of 12 months after undergoing SCE therapy
7. Adequate venous access for apheresis
8. Ability to provide informed consent
9. For female patients only, willingness to use FDA-recommended birth control (http://www.fda.gov/downloads/ForConsumers/ByAudience/ForWomen/FreePublications/UCM356451.pdf) until 6 months post treatment.
10. Must agree to comply with all study requirements and be willing to complete all study visits

Exclusion Criteria:

1. AST or ALT 2 > x upper limit of normal.
2. Abnormal bilirubin (total bilirubin > 1.2 mg/dL, direct bilirubin > 0.4 mg/dL)
3. Creatinine > 2.0 mg/dl.
4. Known coronary artery disease or EKG suggestive of coronary artery disease unless cardiac clearance for apheresis is obtained from a cardiologist.
5. Known active infection such as Hepatitis B, Hepatitis C, or Human Immunodeficiency Virus (HIV)
6. Pregnancy assessed by a positive serum pregnancy test or breastfeeding mothers
7. Use of immunosuppressive medication within one month of enrollment including but not limited to prednisone, cyclosporine, tacrolimus, sirolimus, and chemotherapy.
8. Presence of any other autoimmune diseases (lupus, rheumatoid arthritis, scleroderma, etc.)
9. Anticoagulation other than ASA.
10. Hemoglobin < 10 g/dl or platelets < 100 k/ml
11. Is unable or unwilling to provide informed consent
12. Presence of any other physical or psychological medical condition that, in the opinion of the investigator, would preclude participation
13. Significant cardiovascular diseases that would make use of oral minoxidil inappropriate.

Contacts and Locations

Contacts

Contact: Yong Zhao, MD,PhD; 2019880290; Yong.Zhao@ThroneBio.com

Contact: YONG ZHAO, MD,PhD; Yong.Zhao@ThroneBio.com

Locations

United States, Connecticut

Yale University School of Medicine

New Haven, Connecticut, United States, 06520

Contact: Brett King, MD,PhD

United States, New Jersey

Hackensack Meridian Health

Hackensack, New Jersey, United States, 07601

Contact: Paul Wang, MD

Sponsors and Collaborators

Throne Biotechnologies Inc.

Yale University

Hackensack Meridian Health

More Information

Additional Information:

Throne Biotechnologies Inc 

Publications of Results:

Li Y, Yan B, Wang H, Li H, Li Q, Zhao D, Chen Y, Zhang Y, Li W, Zhang J, Wang S, Shen J, Li Y, Guindi E, Zhao Y. Hair regrowth in alopecia areata patients following Stem Cell Educator therapy. BMC Med. 2015 Apr 20;13:87. doi: 10.1186/s12916-015-0331-6.

Zhao Y, Jiang Z, Zhao T, Ye M, Hu C, Yin Z, Li H, Zhang Y, Diao Y, Li Y, Chen Y, Sun X, Fisk MB, Skidgel R, Holterman M, Prabhakar B, Mazzone T. Reversal of type 1 diabetes via islet β cell regeneration following immune modulation by cord blood-derived multipotent stem cells. BMC Med. 2012 Jan 10;10:3. doi: 10.1186/1741-7015-10-3.

Zhao Y. Stem cell educator therapy and induction of immune balance. Curr Diab Rep. 2012 Oct;12(5):517-23. doi: 10.1007/s11892-012-0308-1. Review.

• Responsible Party: Throne Biotechnologies Inc.
• ClinicalTrials.gov Identifier: NCT04011748
• Other Study ID Numbers: 2019-TH-001
• First Posted: July 8, 2019
• Last Update Posted: June 30, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Alopecia; Alopecia Areata; Hypotrichosis; Hair Diseases; Skin Diseases; Pathological Conditions, Anatomical; Minoxidil; Antihypertensive Agents; Vasodilator Agents