Safety and Efficacy of Injectable Klotho Plasmid Gene Therapy in Humans

NCT ID: NCT07216781

Last Updated: 2025-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-06

Study Completion Date

2026-08-31

Brief Summary

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The purpose of this study is to investigate the safety and efficacy of a gene therapy for Klotho, delivered via a nonviral plasmid in healthy adult volunteers. Additionally, this study seeks to understand the cognitive and health benefits of the Klotho gene therapy.

Detailed Description

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Note that the investigational product will be administered at a site outside of the U.S. which is not under FDA jurisdiction, and only non-treatment pre/post outcome assessments (e.g., cognitive assessments or blood sample collection) occur at the U.S. site.

Participants will take part in cognitive and health testing before and after administration of plasmid-delivered Klotho gene therapy. The method of administration will be subcutaneous injection into abdominal fat deposits. Klotho may improve cognitive function, kidney function, healthspan, and lifespan. Healthy volunteers will partake in a series of blood draws, health screenings, questionnaires, brain perfusion/function measures, and cognitive testing multiple times before and after the intervention.

Conditions

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Healthy Adults

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Non-placebo-controlled trial
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Schedule of Administration and Sample Selection

This arm includes cognitive and health battery at multiple intervals pre- and post-administration of Klotho

Group Type EXPERIMENTAL

Injectable Plasmid Klotho Gene Therapy

Intervention Type GENETIC

Injection of plasmid-delivered Klotho gene therapy

Interventions

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Injectable Plasmid Klotho Gene Therapy

Injection of plasmid-delivered Klotho gene therapy

Intervention Type GENETIC

Eligibility Criteria

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Inclusion Criteria

* Participant is open to morphological change
* If female, participant agrees to maintain contraception
* If female, participant agrees to take a pregnancy test
* If female, participant agrees to a pregnancy waiver

Exclusion Criteria

* Women of childbearing potential who are unwilling or unable to use effective contraception for the duration of the study
* History of cancer diagnosis
* Preexisting medical issues that may be exacerbated by the treatment
* Has received any gene therapy within the past 12 months
* Unwilling or unable to provide written informed consent
Minimum Eligible Age

23 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Minicircle

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Apeiron Center

Austin, Texas, United States

Site Status RECRUITING

GARM Clinic

Roatán, Bay Islands, Honduras

Site Status NOT_YET_RECRUITING

Countries

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United States Honduras

Central Contacts

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Mac Davis

Role: CONTACT

737-701-0823

Facility Contacts

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Mac Davis

Role: primary

737-701-0823

Mayra Hoch

Role: primary

+504 2408-3544

References

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Urakawa I, Yamazaki Y, Shimada T, Iijima K, Hasegawa H, Okawa K, Fujita T, Fukumoto S, Yamashita T. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006 Dec 7;444(7120):770-4. doi: 10.1038/nature05315. Epub 2006 Oct 29.

Reference Type BACKGROUND
PMID: 17086194 (View on PubMed)

Matsumura Y, Aizawa H, Shiraki-Iida T, Nagai R, Kuro-o M, Nabeshima Y. Identification of the human klotho gene and its two transcripts encoding membrane and secreted klotho protein. Biochem Biophys Res Commun. 1998 Jan 26;242(3):626-30. doi: 10.1006/bbrc.1997.8019.

Reference Type BACKGROUND
PMID: 9464267 (View on PubMed)

Masso A, Sanchez A, Bosch A, Gimenez-Llort L, Chillon M. Secreted alphaKlotho isoform protects against age-dependent memory deficits. Mol Psychiatry. 2018 Sep;23(9):1937-1947. doi: 10.1038/mp.2017.211. Epub 2017 Oct 31.

Reference Type BACKGROUND
PMID: 29086766 (View on PubMed)

Masso A, Sanchez A, Gimenez-Llort L, Lizcano JM, Canete M, Garcia B, Torres-Lista V, Puig M, Bosch A, Chillon M. Secreted and Transmembrane alphaKlotho Isoforms Have Different Spatio-Temporal Profiles in the Brain during Aging and Alzheimer's Disease Progression. PLoS One. 2015 Nov 24;10(11):e0143623. doi: 10.1371/journal.pone.0143623. eCollection 2015.

Reference Type BACKGROUND
PMID: 26599613 (View on PubMed)

Imura A, Tsuji Y, Murata M, Maeda R, Kubota K, Iwano A, Obuse C, Togashi K, Tominaga M, Kita N, Tomiyama K, Iijima J, Nabeshima Y, Fujioka M, Asato R, Tanaka S, Kojima K, Ito J, Nozaki K, Hashimoto N, Ito T, Nishio T, Uchiyama T, Fujimori T, Nabeshima Y. alpha-Klotho as a regulator of calcium homeostasis. Science. 2007 Jun 15;316(5831):1615-8. doi: 10.1126/science.1135901.

Reference Type BACKGROUND
PMID: 17569864 (View on PubMed)

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997 Nov 6;390(6655):45-51. doi: 10.1038/36285.

Reference Type BACKGROUND
PMID: 9363890 (View on PubMed)

Imura A, Iwano A, Tohyama O, Tsuji Y, Nozaki K, Hashimoto N, Fujimori T, Nabeshima Y. Secreted Klotho protein in sera and CSF: implication for post-translational cleavage in release of Klotho protein from cell membrane. FEBS Lett. 2004 May 7;565(1-3):143-7. doi: 10.1016/j.febslet.2004.03.090.

Reference Type BACKGROUND
PMID: 15135068 (View on PubMed)

Gupta S, Moreno AJ, Wang D, Leon J, Chen C, Hahn O, Poon Y, Greenberg K, David N, Wyss-Coray T, Raftery D, Promislow DEL, Dubal DB. KL1 Domain of Longevity Factor Klotho Mimics the Metabolome of Cognitive Stimulation and Enhances Cognition in Young and Aging Mice. J Neurosci. 2022 May 11;42(19):4016-4025. doi: 10.1523/JNEUROSCI.2458-21.2022. Epub 2022 Apr 15.

Reference Type BACKGROUND
PMID: 35428698 (View on PubMed)

Dubal DB, Yokoyama JS, Zhu L, Broestl L, Worden K, Wang D, Sturm VE, Kim D, Klein E, Yu GQ, Ho K, Eilertson KE, Yu L, Kuro-o M, De Jager PL, Coppola G, Small GW, Bennett DA, Kramer JH, Abraham CR, Miller BL, Mucke L. Life extension factor klotho enhances cognition. Cell Rep. 2014 May 22;7(4):1065-76. doi: 10.1016/j.celrep.2014.03.076. Epub 2014 May 10.

Reference Type BACKGROUND
PMID: 24813892 (View on PubMed)

Davidsohn N, Pezone M, Vernet A, Graveline A, Oliver D, Slomovic S, Punthambaker S, Sun X, Liao R, Bonventre JV, Church GM. A single combination gene therapy treats multiple age-related diseases. Proc Natl Acad Sci U S A. 2019 Nov 19;116(47):23505-23511. doi: 10.1073/pnas.1910073116. Epub 2019 Nov 4.

Reference Type BACKGROUND
PMID: 31685628 (View on PubMed)

Chen CD, Podvin S, Gillespie E, Leeman SE, Abraham CR. Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19796-801. doi: 10.1073/pnas.0709805104. Epub 2007 Dec 3.

Reference Type BACKGROUND
PMID: 18056631 (View on PubMed)

Castner SA, Gupta S, Wang D, Moreno AJ, Park C, Chen C, Poon Y, Groen A, Greenberg K, David N, Boone T, Baxter MG, Williams GV, Dubal DB. Longevity factor klotho enhances cognition in aged nonhuman primates. Nat Aging. 2023 Aug;3(8):931-937. doi: 10.1038/s43587-023-00441-x. Epub 2023 Jul 3.

Reference Type BACKGROUND
PMID: 37400721 (View on PubMed)

Arking DE, Krebsova A, Macek M Sr, Macek M Jr, Arking A, Mian IS, Fried L, Hamosh A, Dey S, McIntosh I, Dietz HC. Association of human aging with a functional variant of klotho. Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):856-61. doi: 10.1073/pnas.022484299. Epub 2002 Jan 15.

Reference Type BACKGROUND
PMID: 11792841 (View on PubMed)

Abraham CR, Mullen PC, Tucker-Zhou T, Chen CD, Zeldich E. Klotho Is a Neuroprotective and Cognition-Enhancing Protein. Vitam Horm. 2016;101:215-38. doi: 10.1016/bs.vh.2016.02.004. Epub 2016 Mar 22.

Reference Type BACKGROUND
PMID: 27125744 (View on PubMed)

Other Identifiers

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MINICIRCLE-KLO

Identifier Type: -

Identifier Source: org_study_id

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