Healthy VolunteersPhase 1NCT04208152

A First-in-Human Study of Single and Multiple Doses of anle138b in Healthy Subjects

A Phase 1 study testing anle138b in people with Healthy Volunteers, run by MODAG GmbH at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to determine the safety, tolerability and blood levels of orally administered anle138b in healthy subjects. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers
What is being tested?: anle138b
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 68 participants
Where: 1 siteUnited Kingdom
Study dates: 6 Dec 2019to 4 Aug 2020
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy males or women of no child bearing potential
Age 18 to 55 years of age at the time of signing informed consent
Body mass index (BMI) of 18.5 to 30.0 kg/m2 as measured at screening
Must be willing and able to communicate and participate in the whole study
Must provide written informed consent
Must agree to adhere to the contraception requirements defined in Section 9.4
In the investigator's opinion, subject is able to understand the nature of the study and any risks involved in participation, and willing to cooperate and comply with the protocol restrictions and requirements.

Who cannot join

Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
Subjects who have previously been enrolled in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2 or Part 3; subjects who have taken part in Part 2 are not permitted to take part in Part 3.
History of any drug or alcohol abuse in the past 2 years.
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).
A confirmed positive alcohol breath test at screening or admission.

Show all 25Show fewer

Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission.
Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months.
Females of childbearing potential including those who are pregnant or lactating (all female subjects must have a negative urine pregnancy test at screening and serum pregnancy test on admission). A woman is considered of childbearing potential unless she is permanently sterile (hysterectomy, bilateral salpingectomy and bilateral oophorectomy) or is postmenopausal (had no menses for 12 months without an alternative medical cause and a serum follicle stimulating hormone concentration ≥40 IU/L).
Subjects with pregnant or lactating partners.
Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in Appendix 1). Subjects with Gilbert's Syndrome are allowed. In addition the ALT and gamma glutamyl transferase (GGT) concentrations should not exceed the upper limit of normal (ULN) at screening and admission.
Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in Appendix 1) at screening or admission.
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <70 mL/min using the Cockcroft-Gault equation.
History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator.
Serious adverse reaction or serious hypersensitivity to any drug or the IMP excipients.
Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
Donation or loss of greater than 400 mL of blood within the previous 3 months.
Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than 4 g of paracetamol per day or HRT) in the 14 days before IMP administration (See Section 11.4). Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the PI.
Failure to satisfy the investigator of fitness to participate for any other reason.
In Part 3, subjects must be able to eat 90% of the US Food and Drug Administration (FDA)-approved high-fat breakfast, including bacon.
Subjects with a previous history of difficulty in swallowing tablets or capsules, or an anticipated problem with swallowing a large number of capsules.
Blood pressure (supine) at Screening or admission outside the range: 90 to 140 mmHg for subjects <45 years or 90 to 160 mmHg for subjects >45 years for systolic BP or 40 to 90 mmHg for diastolic BP; and pulse rate outside the range of 40 to 100 bpm, unless deemed not clinically significant by the investigator and the sponsor's medical monitor.
Subjects with a history of cholecystectomy or gall stones.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Quotient Sciences
Nottingham, NG11 6JS

Other trials in United Kingdom

About this study

Official title: A First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of anle138b in Healthy Male and Female Subjects

The purpose of this study is to determine the safety, tolerability and blood levels of orally administered anle138b in healthy subjects.

Read the detailed description

This is a single-centre, study of double-blind, randomised, placebo-controlled single ascending doses (SAD) and multiple ascending doses (MAD) of anle138b in healthy subjects in study Parts 1 and 2. In study Part 3 the effect of food (FES) on the safety and PK of anle138b in healthy subjects is examined.

In the SAD cohorts, subjects will be randomly assigned to receive a single oral dose of active investigational medicinal product (IMP) or matching placebo in a sequential escalating manner with sufficient time planned between dose groups to allow interim review of the data.

In the MAD cohorts, subjects will be randomly assigned to receive oral doses of active IMP or matching placebo once daily (QD) for 7 days, in a sequential escalating manner with sufficient time planned between dose groups to allow interim review of the data.

In the FES, the effect of food on the safety and PK of anle138b is explored by administering a single dose of IMP after a high-fat breakfast. Subjects will be randomly assigned to one of 2 treatment sequence to receive anle138b in the fed or fasted state over 2 periods.

Conditions: Healthy Volunteers
Being tested: anle138b, Placebo
Keywords: anle138b, alpha-Synuclein, Oligomer modulator, Parkinson Disease, Multiple System Atrophy, Neurodegenerative diseases, Alzheimer Disease, Tauopathies, Amyloid
Medical subject headings: Parkinson Disease 4, Autosomal Dominant Lewy Body, Parkinson Disease, Multiple System Atrophy, Neurodegenerative Diseases, Alzheimer Disease, Tauopathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

anle138bDrug
capsule containing excipient and anle138b
PlaceboDrug
matching placebo capsule containing excipient

Study groups in NCT04208152
Study group	Role	What they receive
anle138b	Active comparator	Dosage: 50 mg and higher Dosage form: capsule Frequency: once daily Duration: One day for SAD and seven days for MAD Receives: Drug: anle138b
placebo	Placebo comparator	Matching placebo Dosage form: capsule Frequency: once daily Duration: One day for SAD and seven days for MAD Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of treatment-emergent adverse events in healthy volunteers with single ascending doses of anle138b (Part 1)
Adverse events (AEs)
Measured: Day 1 to day 30 post dose
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with single ascending doses of anle138b (Part 1)
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent changes in vital signs in healthy volunteers with single ascending doses of anle138b (Part 1)
Blood pressure, heart rate, oral temperature
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent ECG changes in healthy volunteers with single ascending doses of anle138b (Part 1)
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent changes in physical examination in healthy volunteers with single ascending doses of anle138b (Part 1)
physical examination findings
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent adverse events in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Adverse events (AEs)
Measured: Day 1 to day 30 post dose
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with multiple ascending doses of anle138b (Part 2)
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent changes in vital signs in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Blood pressure, heart rate, oral temperature
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent ECG changes in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent changes in physical examination in healthy volunteers with multiple ascending doses of anle138b (Part 2)
physical examination findings
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent adverse events in healthy volunteers with a single dose of anle138b both the fasted and fed state (Part 3)
Adverse events (AEs)
Measured: Day 1 to day 30 post dose.
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent changes in vital signs in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Blood pressure, heart rate, oral temperature
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent ECG changes in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Measured: Day 1 to day 7 post dose
Incidence of treatment-emergent changes in physical examination in healthy volunteers with single ascending doses of anle138b both in the fasted and in the fed state (Part 3)
physical examination findings
Measured: Day 1 to day 7 post dose

Secondary outcomes (22)

Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time prior to the first measurable concentration of anle138b.
Time prior to the first measurable concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time of maximum observed concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Maximum observed concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Area under the curve from 0 time to 24 h post-dose of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Area under the curve from 0 time to the last measurable concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Area under the curve from 0 time extrapolated to infinity of anle138b levels.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Percentage of area under the curve (0-inf) extrapolated beyond the last measurable concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Slope of the apparent elimination phase of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Apparent elimination half-life of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Mean residence time from 0 time to the last measurable concentration after extravascular administration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Mean residence time extrapolated to infinity after extravascular administration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Time of maximum observed concentration of anle138b
Measured: Day 1 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Maximum observed concentration of anle138b
Measured: Day 1 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Area under the curve over the dosing interval from time 0 to tau of anle138b
Measured: Day 1 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Slope of the apparent elimination phase (last dose only) of anle138b
Measured: Day 7 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Apparent elimination half-life (last dose only) of anle138b
Measured: Day 1 to day 9
Oral pharmacokinetics (PK) of single (Part 1) and multiple (Part 2) ascending doses of anle138b in the fasted state
Accumulation Ratio based on Cmax repeated dose /Cmax single dose of anle138b
Measured: Day 1 to day 9
Oral pharmacokinetics (PK) of single (Part 1) and multiple (Part 2) ascending doses of anle138b in the fasted state
Accumulation Ratio based on area under the curve (0 tau) repeated dose/AUC(0 tau) single dose of anle138b
Measured: Day 1 to day 9
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states.
Maximum observed concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states.
Area under the curve from 0 time to the last measurable concentration of anle138b.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states
Area under the curve from 0 time extrapolated to infinity of anle138b levels.
Measured: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states
Percentage of area under the curve (0-inf) extrapolated beyond the last measurable concentration of anle138b.
Measured: From dosing to 48 hours post dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Dec 20194 Aug 2020

First posted23 Dec 2019
Study start6 Dec 2019
Primary completion4 Aug 2020
Study completion4 Aug 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (7)Papers the sponsor has linked to this study.
Other trials for Healthy VolunteersStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 68 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04208152
Sponsor's protocol ID: anle138b-P1-01
Other IDs: 2019-004218-33, 2019
Status last verified: Aug 2020
First submitted: 16 Dec 2019
Last updated: 6 Aug 2020
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, Prix C, Pan-Montojo F, Bertsch U, Mitteregger-Kretzschmar G, Geissen M, Eiden M, Leidel F, Hirschberger T, Deeg AA, Krauth JJ, Zinth W, Tavan P, Pilger J, Zweckstetter M, Frank T, Bahr M, Weishaupt JH, Uhr M, Urlaub H, Teichmann U, Samwer M, Botzel K, Groschup M, Kretzschmar H, Griesinger C, Giese A. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease. Acta Neuropathol. 2013 Jun;125(6):795-813. doi: 10.1007/s00401-013-1114-9. Epub 2013 Apr 19.
PubMed 23604588
Levin J, Schmidt F, Boehm C, Prix C, Botzel K, Ryazanov S, Leonov A, Griesinger C, Giese A. The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset. Acta Neuropathol. 2014 May;127(5):779-80. doi: 10.1007/s00401-014-1265-3. Epub 2014 Mar 11. No abstract available.
PubMed 24615514
Heras-Garvin A, Weckbecker D, Ryazanov S, Leonov A, Griesinger C, Giese A, Wenning GK, Stefanova N. Anle138b modulates alpha-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019 Feb;34(2):255-263. doi: 10.1002/mds.27562. Epub 2018 Nov 19.
PubMed 30452793
Wegrzynowicz M, Bar-On D, Calo' L, Anichtchik O, Iovino M, Xia J, Ryazanov S, Leonov A, Giese A, Dalley JW, Griesinger C, Ashery U, Spillantini MG. Depopulation of dense alpha-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model. Acta Neuropathol. 2019 Oct;138(4):575-595. doi: 10.1007/s00401-019-02023-x. Epub 2019 May 31.
PubMed 31165254
Wagner J, Krauss S, Shi S, Ryazanov S, Steffen J, Miklitz C, Leonov A, Kleinknecht A, Goricke B, Weishaupt JH, Weckbecker D, Reiner AM, Zinth W, Levin J, Ehninger D, Remy S, Kretzschmar HA, Griesinger C, Giese A, Fuhrmann M. Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies. Acta Neuropathol. 2015 Nov;130(5):619-31. doi: 10.1007/s00401-015-1483-3. Epub 2015 Oct 6.
PubMed 26439832
Martinez Hernandez A, Urbanke H, Gillman AL, Lee J, Ryazanov S, Agbemenyah HY, Benito E, Jain G, Kaurani L, Grigorian G, Leonov A, Rezaei-Ghaleh N, Wilken P, Arce FT, Wagner J, Fuhrmann M, Caruana M, Camilleri A, Vassallo N, Zweckstetter M, Benz R, Giese A, Schneider A, Korte M, Lal R, Griesinger C, Eichele G, Fischer A. The diphenylpyrazole compound anle138b blocks Abeta channels and rescues disease phenotypes in a mouse model for amyloid pathology. EMBO Mol Med. 2018 Jan;10(1):32-47. doi: 10.15252/emmm.201707825.
PubMed 29208638
Levin J, Sing N, Melbourne S, Morgan A, Mariner C, Spillantini MG, Wegrzynowicz M, Dalley JW, Langer S, Ryazanov S, Leonov A, Griesinger C, Schmidt F, Weckbecker D, Prager K, Matthias T, Giese A. Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial. EBioMedicine. 2022 Jun;80:104021. doi: 10.1016/j.ebiom.2022.104021. Epub 2022 Apr 29.
PubMed 35500536

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 6 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of anle138b in Healthy Male and Female Subjects
ClinicalTrials.gov ID: NCT04208152
Acronym / sponsor ID: anle138b-P1-01
Conditions: Healthy Volunteers
Keywords: anle138b, alpha-Synuclein, Oligomer modulator, Parkinson Disease, Multiple System Atrophy, Neurodegenerative diseases, Alzheimer Disease, Tauopathies
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 68 participants (actual)
Lead sponsor: MODAG GmbHIndustry (pharma, biotech, devices)
Collaborators: Quotient Sciences, Aptuit
Study start: 6 Dec 2019 (actual)
Primary completion: 4 Aug 2020 (actual)
Study completion: 4 Aug 2020 (actual)
First posted: 23 Dec 2019 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to determine the safety, tolerability and blood levels of orally administered anle138b in healthy subjects.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
anle138b	Active comparator	Drug: anle138bDosage: 50 mg and higher Dosage form: capsule Frequency: once daily Duration: One day for SAD and seven days for MAD
placebo	Placebo comparator	Drug: PlaceboMatching placebo Dosage form: capsule Frequency: once daily Duration: One day for SAD and seven days for MAD

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Healthy males or women of no child bearing potential
Age 18 to 55 years of age at the time of signing informed consent
Body mass index (BMI) of 18.5 to 30.0 kg/m2 as measured at screening
Must be willing and able to communicate and participate in the whole study
Must provide written informed consent

Key exclusion criteria (25 listed)

Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
Subjects who have previously been enrolled in this study. Subjects who have taken part in Part 1 are not permitted to take part in Part 2 or Part 3; subjects who have taken part in Part 2 are not permitted to take part in Part 3.
History of any drug or alcohol abuse in the past 2 years.
Regular alcohol consumption in males >21 units per week and females >14 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 units = 125 mL glass of wine, depending on type).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
anle138bcapsule containing excipient and anle138b	Drug	anle138b
Placebomatching placebo capsule containing excipient	Drug	placebo

Primary outcome

Incidence of treatment-emergent adverse events in healthy volunteers with single ascending doses of anle138b (Part 1)
Time frame: Day 1 to day 30 post dose
Adverse events (AEs)
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with single ascending doses of anle138b (Part 1)
Time frame: Day 1 to day 7 post dose
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Incidence of treatment-emergent changes in vital signs in healthy volunteers with single ascending doses of anle138b (Part 1)
Time frame: Day 1 to day 7 post dose
Blood pressure, heart rate, oral temperature
Incidence of treatment-emergent ECG changes in healthy volunteers with single ascending doses of anle138b (Part 1)
Time frame: Day 1 to day 7 post dose
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Incidence of treatment-emergent changes in physical examination in healthy volunteers with single ascending doses of anle138b (Part 1)
Time frame: Day 1 to day 7 post dose
physical examination findings
Incidence of treatment-emergent adverse events in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time frame: Day 1 to day 30 post dose
Adverse events (AEs)
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time frame: Day 1 to day 7 post dose
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Incidence of treatment-emergent changes in vital signs in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time frame: Day 1 to day 7 post dose
Blood pressure, heart rate, oral temperature
Incidence of treatment-emergent ECG changes in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time frame: Day 1 to day 7 post dose
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Incidence of treatment-emergent changes in physical examination in healthy volunteers with multiple ascending doses of anle138b (Part 2)
Time frame: Day 1 to day 7 post dose
physical examination findings
Incidence of treatment-emergent adverse events in healthy volunteers with a single dose of anle138b both the fasted and fed state (Part 3)
Time frame: Day 1 to day 30 post dose.
Adverse events (AEs)
Incidence of treatment-emergent changes in clinical laboratory parameters in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Time frame: Day 1 to day 7 post dose
clinical laboratory tests including hematology and clinical chemistry including renal function tests, hepatic enzymes, electrolytes and creatine kinase
Incidence of treatment-emergent changes in vital signs in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Time frame: Day 1 to day 7 post dose
Blood pressure, heart rate, oral temperature
Incidence of treatment-emergent ECG changes in healthy volunteers with a single dose of anle138b both in the fasted and in the fed state (Part 3)
Time frame: Day 1 to day 7 post dose
Electrocardiogram (ECG) parameters including QT interval corrected for heart rate using Fridericia's formula (QTcF)
Incidence of treatment-emergent changes in physical examination in healthy volunteers with single ascending doses of anle138b both in the fasted and in the fed state (Part 3)
Time frame: Day 1 to day 7 post dose
physical examination findings

22 secondary outcomes

Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of single (Part 1) ascending doses of anle138b in the fasted state
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 1 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 1 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 1 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 7 to day 9
Oral pharmacokinetics (PK) of multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 1 to day 9
Oral pharmacokinetics (PK) of single (Part 1) and multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 1 to day 9
Oral pharmacokinetics (PK) of single (Part 1) and multiple (Part 2) ascending doses of anle138b in the fasted state
Time frame: Day 1 to day 9
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states.
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states.
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states
Time frame: From dosing to 48 hours post dosing
Oral pharmacokinetics (PK) (Part 3) for anle138b in the fed and fasted states
Time frame: From dosing to 48 hours post dosing

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2020.
Background: PubMed 23604588Wagner J, Ryazanov S, Leonov A, Levin J, Shi S, Schmidt F, Prix C, Pan-Montojo F, Bertsch U, Mitteregger-Kretzschmar G, Geissen M, Eiden M, Leidel F, Hirschberger T, Deeg AA, Krauth JJ, Zinth W, Tavan P, Pilger J, Zweckstetter M, Frank T, Bahr M, Weishaupt JH, Uhr M, Urlaub H, Teichmann U, Samwer M, Botzel K, Groschup M, Kretzschmar H, Griesinger C, Giese A. Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson's disease. Acta Neuropathol. 2013 Jun;125(6):795-813. doi: 10.1007/s00401-013-1114-9. Epub 2013 Apr 19.
Background: PubMed 24615514Levin J, Schmidt F, Boehm C, Prix C, Botzel K, Ryazanov S, Leonov A, Griesinger C, Giese A. The oligomer modulator anle138b inhibits disease progression in a Parkinson mouse model even with treatment started after disease onset. Acta Neuropathol. 2014 May;127(5):779-80. doi: 10.1007/s00401-014-1265-3. Epub 2014 Mar 11. No abstract available.
Background: PubMed 30452793Heras-Garvin A, Weckbecker D, Ryazanov S, Leonov A, Griesinger C, Giese A, Wenning GK, Stefanova N. Anle138b modulates alpha-synuclein oligomerization and prevents motor decline and neurodegeneration in a mouse model of multiple system atrophy. Mov Disord. 2019 Feb;34(2):255-263. doi: 10.1002/mds.27562. Epub 2018 Nov 19.
Background: PubMed 31165254Wegrzynowicz M, Bar-On D, Calo' L, Anichtchik O, Iovino M, Xia J, Ryazanov S, Leonov A, Giese A, Dalley JW, Griesinger C, Ashery U, Spillantini MG. Depopulation of dense alpha-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model. Acta Neuropathol. 2019 Oct;138(4):575-595. doi: 10.1007/s00401-019-02023-x. Epub 2019 May 31.
Background: PubMed 26439832Wagner J, Krauss S, Shi S, Ryazanov S, Steffen J, Miklitz C, Leonov A, Kleinknecht A, Goricke B, Weishaupt JH, Weckbecker D, Reiner AM, Zinth W, Levin J, Ehninger D, Remy S, Kretzschmar HA, Griesinger C, Giese A, Fuhrmann M. Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies. Acta Neuropathol. 2015 Nov;130(5):619-31. doi: 10.1007/s00401-015-1483-3. Epub 2015 Oct 6.
Background: PubMed 29208638Martinez Hernandez A, Urbanke H, Gillman AL, Lee J, Ryazanov S, Agbemenyah HY, Benito E, Jain G, Kaurani L, Grigorian G, Leonov A, Rezaei-Ghaleh N, Wilken P, Arce FT, Wagner J, Fuhrmann M, Caruana M, Camilleri A, Vassallo N, Zweckstetter M, Benz R, Giese A, Schneider A, Korte M, Lal R, Griesinger C, Eichele G, Fischer A. The diphenylpyrazole compound anle138b blocks Abeta channels and rescues disease phenotypes in a mouse model for amyloid pathology. EMBO Mol Med. 2018 Jan;10(1):32-47. doi: 10.15252/emmm.201707825.
Derived from this study: PubMed 35500536Levin J, Sing N, Melbourne S, Morgan A, Mariner C, Spillantini MG, Wegrzynowicz M, Dalley JW, Langer S, Ryazanov S, Leonov A, Griesinger C, Schmidt F, Weckbecker D, Prager K, Matthias T, Giese A. Safety, tolerability and pharmacokinetics of the oligomer modulator anle138b with exposure levels sufficient for therapeutic efficacy in a murine Parkinson model: A randomised, double-blind, placebo-controlled phase 1a trial. EBioMedicine. 2022 Jun;80:104021. doi: 10.1016/j.ebiom.2022.104021. Epub 2022 Apr 29.
MODAG GmbH - Sponsor homepageLink provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Nand Singh, BSc, MD, DPM, MFPM principal investigator

Quotient Sciences Mere Way Ruddington Fields Ruddington Nottingham NG11 6JS, UK

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing anle138b in people with Healthy Volunteers, run by MODAG GmbH at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment-emergent adverse events in healthy volunteers with single ascending doses of anle138b (Part 1) (time frame: Day 1 to day 30 post dose). The study lists 15 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04208152, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2020.