StrokePhase 1NCT04742062
First in Human Clinical Trial of ApTOLL in Healthy Volunteers
A Phase 1 study testing ApTOLL in people with Stroke, run by aptaTargets S.L. at 1 site in Spain.
Trial summary
This is a Phase I, first-in-human, dose ascending, randomized, placebo-controlled clinical study to assess the tolerability and pharmacokinetics of ApTOLL in healthy volunteers. ApTOLL is an aptamer able to antagonize TLR4 receptor and, therefore, to reduce the inflammatory response. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Stroke
- What is being tested?
- ApTOLL
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteSpain
- Study dates
- 18 Jul 2019to 20 Mar 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
- Male or female subjects (women without possibility of becoming pregnant) willing and able to give their written consent to participate in the trial.
- Healthy subjects aged within: 18 to 55 years (limits included).
- Clinical history and physical examination results within normality.
- Vital signs and electrocardiogram without clinically significant pathologic abnormalities and with QTc (Corrected QT space) values lower than 450 ms.
- Body weight between 65 and 85 kg, inclusive.
- BMI (Body Mass Index) between 19.0 and 30.0 kg/m2.
- No clinically significant abnormalities in haematology, biochemistry, serology (Ag HBV (Hepatitis B Virus), HCV (Hepatitis C Virus) antibodies, HIV (Human Immunodeficiency Virus) antibodies) and urine tests.
Who cannot join
- Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment.
- Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
- Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
- Subject having at screening examination a sitting blood pressure more than or equal to 140/90 mm Hg or lower than or equal to 90/50 mmHg.
- Subject having at screening examination a pulse more than 100 beats per minute or a body temperature more than 37.7 °C. or a respiratory rate outside the normal range of (14-20 breath per minute).
- History of any treatment for cancer within the past 2 years, other than basal cell or squamous cell carcinoma of the skin.
Show all 19Show fewer
- Clinically significant abnormalities in screening laboratory tests.
- Any prescription, over-the-counter and herbal medications within 10 days prior to study dosing.
- Use of an investigational drug within 3 months prior to dosing in this study.
- Psychiatric history of current or past psychosis, bipolar disorder, clinical depression, or anxiety disorder requiring chronic medication within the past 5 years.
- Pregnant or breastfeeding women.
- History of substance abuse, including alcohol.
- Smokers.
- History of substance or drug dependence, or positive urine drug screen at screening visit.
- History of head injury.
- History of sensitivity to any drug.
- Having donated blood in the last month before start of the study.
- Any reason or opinion of the investigator that would prevent the subject from participation in the study.
- Inability to follow the instructions or an unwillingness to collaborate during the study.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Clinical Pharmacology Department. Hospital Universitario de La Princesa
Madrid, 28006
About this study
Official title: First in Human Dose Ascending, Randomized, Placebo-Controlled Clinical Trial to Assess Tolerability and Pharmacokinetics of ApTOLL in Healthy Volunteers
This is a Phase I, first-in-human, dose ascending, randomized, placebo-controlled clinical study to assess the tolerability and pharmacokinetics of ApTOLL in healthy volunteers. ApTOLL is an aptamer able to antagonize TLR4 receptor and, therefore, to reduce the inflammatory response.
Read the detailed description
This Phase I clinical trial is divided in two parts: the first part (part A) is a single dose escalation study and the second (part B) is a multiple dose study. Both are performed in healthy volunteers.
- First part: a single dose, i.v. administration (slow infusion), dose escalation with a maximum of 7 single dose levels, randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
- Second part: a multiple dose, i.v. administration (slow infusion), randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
The main objectives of this study are:
- To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after single dose administration in fasting conditions, following an ascending dosing scheme.
- To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after multiple dose administration in fasting conditions.
- Conditions
- Stroke
- Being tested
- ApTOLL, Placebo
- Keywords
- Healthy volunteers, ApTOLL
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApTOLLDrug
ApTOLL is a Toll-like receptor 4 (TLR4) antagonist, a receptor that is involved in innate immune responses but also responds to tissue damage, and therefore it is directly involved in a large number of diseases where the inflammatoryy response is involved. ApTOLL has demonstrated specific binding to human TLR4 as well as a TLR4 antagonistic effect, reducing inflammation and improving outcome after different disease models.
PlaceboOther
100 mL 0.9% Sodium Chloride solution
| Study group | Role | What they receive |
|---|---|---|
| ApTOLL single dose | Active comparator | ApTOLL is administered intravenously in a single ascending dose pattern in seven dose levels (0.7mg - 70mg). Levels 1 - 3 include one subject per level and levels 4 - 7 include six subjects per level (1 sentinel + 5 subjects). Receives: Drug: ApTOLL |
| Placebo single dose | Placebo comparator | Placebo is administered intravenously during seven dose levels. Levels 1 - 3 include one subject per level and levels 4 - 7 include two subjects per level (1 sentinel + 1 subject). Receives: Other: Placebo |
| ApTOLL multiple dose | Active comparator | ApTOLL is administered intravenously every eight hours during 24h (21mg). This arm includes six subjects (1 sentinel + 5 subjects). Receives: Drug: ApTOLL |
| Placebo multiple dose | Placebo comparator | Placebo is administered intravenously every eight hours during 24h. This arm includes twosubjects (1 sentinel + 1 subject). Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse Events as assessed by CTCAE v4.0
Adverse Events that occur during the study
Measured: From dosing to follow-up (day 15 after dosing)
Peak Plasma Concentration
Peak Plasma Concentration (Cmax)
Measured: Predose and at different times up to 72 hours post-dose
Area under the plasma concentration
Area under the plasma concentration versus time curve (AUC)
Measured: Predose and at different times up to 72 hours post-dose
Secondary outcomes (6)
Vital signs
Heart Rate
Measured: From screening to follow-up (day 15 after dosing)
Vital signs
Blood Presure
Measured: From screening to follow-up (day 15 after dosing)
Vital signs
Respiratory Rate
Measured: From screening to follow-up (day 15 after dosing)
Vital signs
Body Temperature
Measured: From screening to follow-up (day 15 after dosing)
Laboratory determinations
Number of patients with treatment-related alterations coagulation parameters (Protrombine Time (PT) and activated Partial Tromboplastine Time (aPTT))
Measured: From screening to follow-up (day 15 after dosing)
Laboratory determinations
Number of patients with treatment-related alterations Complement Factors activation determined in blood
Measured: From screening to follow-up (day 15 after dosing)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2021
- Study start18 Jul 2019
- Primary completion27 Feb 2020
- Study completion20 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for StrokeStudies 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
- Sequential
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- aptaTargets S.L.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ministry of Science and Innovation, Spain, Anagram
- Responsible party
- Sponsor
- Investigators
- Dolores Ochoa, MD, PhD, Principal investigator, Clinical Trials Unit. Hospital Universitario La PrincesaMacarena Hernández, PhD, Study director, aptaTargets S.L.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04742062
- Sponsor's protocol ID
- ApTOLL-FIH-01
- Status last verified
- Jan 2021
- First submitted
- 26 Jan 2021
- Last updated
- 17 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: All the data from this study are going to be published.
Publications
Duran-Laforet V, Pena-Martinez C, Garcia-Culebras A, Alzamora L, Moro MA, Lizasoain I. Pathophysiological and pharmacological relevance of TLR4 in peripheral immune cells after stroke. Pharmacol Ther. 2021 Dec;228:107933. doi: 10.1016/j.pharmthera.2021.107933. Epub 2021 Jun 24.
PubMed 34174279
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First in Human Dose Ascending, Randomized, Placebo-Controlled Clinical Trial to Assess Tolerability and Pharmacokinetics of ApTOLL in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT04742062
- Acronym / sponsor ID
- ApTOLL-FIH-01
- Conditions
- Stroke
- Keywords
- Healthy volunteers, ApTOLL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- aptaTargets S.L.Industry (pharma, biotech, devices)
- Collaborators
- Ministry of Science and Innovation, Spain, Anagram
- Study start
- 18 Jul 2019 (actual)
- Primary completion
- 27 Feb 2020 (actual)
- Study completion
- 20 Mar 2020 (actual)
- First posted
- 5 Feb 2021 (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.
This is a Phase I, first-in-human, dose ascending, randomized, placebo-controlled clinical study to assess the tolerability and pharmacokinetics of ApTOLL in healthy volunteers. ApTOLL is an aptamer able to antagonize TLR4 receptor and, therefore, to reduce the inflammatory response.
Detailed description
This Phase I clinical trial is divided in two parts: the first part (part A) is a single dose escalation study and the second (part B) is a multiple dose study. Both are performed in healthy volunteers.
- First part: a single dose, i.v. administration (slow infusion), dose escalation with a maximum of 7 single dose levels, randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
- Second part: a multiple dose, i.v. administration (slow infusion), randomized, double-blind, placebo-controlled (saline solution), in healthy subjects.
The main objectives of this study are:
- To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after single dose administration in fasting conditions, following an ascending dosing scheme.
- To evaluate the tolerability and pharmacokinetic characteristics of ApTOLL in healthy volunteers, after multiple dose administration in fasting conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ApTOLL single dose | Active comparator | Drug: ApTOLLApTOLL is administered intravenously in a single ascending dose pattern in seven dose levels (0.7mg - 70mg). Levels 1 - 3 include one subject per level and levels 4 - 7 include six subjects per level (1 sentinel + 5 subjects). |
| Placebo single dose | Placebo comparator | Other: PlaceboPlacebo is administered intravenously during seven dose levels. Levels 1 - 3 include one subject per level and levels 4 - 7 include two subjects per level (1 sentinel + 1 subject). |
| ApTOLL multiple dose | Active comparator | Drug: ApTOLLApTOLL is administered intravenously every eight hours during 24h (21mg). This arm includes six subjects (1 sentinel + 5 subjects). |
| Placebo multiple dose | Placebo comparator | Other: PlaceboPlacebo is administered intravenously every eight hours during 24h. This arm includes twosubjects (1 sentinel + 1 subject). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or female subjects (women without possibility of becoming pregnant) willing and able to give their written consent to participate in the trial.
- Healthy subjects aged within: 18 to 55 years (limits included).
- Clinical history and physical examination results within normality.
- Vital signs and electrocardiogram without clinically significant pathologic abnormalities and with QTc (Corrected QT space) values lower than 450 ms.
- Body weight between 65 and 85 kg, inclusive.
Key exclusion criteria (19 listed)
- Any chronic medical condition (such as type 1 diabetes) requiring chronic treatment.
- Evidence of active infection requiring antibiotic therapy within 14 days prior to screening.
- Medical history of vasculitis or any autoimmune disease excluding seasonal allergic rhinitis and childhood history of atopic dermatitis.
- Subject having at screening examination a sitting blood pressure more than or equal to 140/90 mm Hg or lower than or equal to 90/50 mmHg.
- Subject having at screening examination a pulse more than 100 beats per minute or a body temperature more than 37.7 °C. or a respiratory rate outside the normal range of (14-20 breath per minute).
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 |
|---|---|---|
| ApTOLLApTOLL is a Toll-like receptor 4 (TLR4) antagonist, a receptor that is involved in innate immune responses but also responds to tissue damage, and therefore it is directly involved in a large number of diseases where the inflammatoryy response is involved. ApTOLL has demonstrated specific binding to human TLR4 as well as a TLR4 antagonistic effect, reducing inflammation and improving outcome after different disease models. | Drug | ApTOLL multiple dose, ApTOLL single dose |
| Placebo100 mL 0.9% Sodium Chloride solution | Other | Placebo multiple dose, Placebo single dose |
Primary outcome
Incidence of Adverse Events as assessed by CTCAE v4.0
Time frame: From dosing to follow-up (day 15 after dosing)
Adverse Events that occur during the study
Peak Plasma Concentration
Time frame: Predose and at different times up to 72 hours post-dose
Peak Plasma Concentration (Cmax)
Area under the plasma concentration
Time frame: Predose and at different times up to 72 hours post-dose
Area under the plasma concentration versus time curve (AUC)
6 secondary outcomes
Vital signs
Time frame: From screening to follow-up (day 15 after dosing)
Vital signs
Time frame: From screening to follow-up (day 15 after dosing)
Vital signs
Time frame: From screening to follow-up (day 15 after dosing)
Vital signs
Time frame: From screening to follow-up (day 15 after dosing)
Laboratory determinations
Time frame: From screening to follow-up (day 15 after dosing)
Laboratory determinations
Time frame: From screening to follow-up (day 15 after 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 17 Mar 2022.
- Derived from this study: PubMed 34174279Duran-Laforet V, Pena-Martinez C, Garcia-Culebras A, Alzamora L, Moro MA, Lizasoain I. Pathophysiological and pharmacological relevance of TLR4 in peripheral immune cells after stroke. Pharmacol Ther. 2021 Dec;228:107933. doi: 10.1016/j.pharmthera.2021.107933. Epub 2021 Jun 24.
- Biotechnology company specialized in therapeutic aptamersLink provided by the sponsor.
- Individual participant dataSharing planned: No. All the data from this study are going to be published.
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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.
Dolores Ochoa, MD, PhD principal investigator
Clinical Trials Unit. Hospital Universitario La Princesa
Macarena Hernández, PhD study director
aptaTargets S.L.
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 ApTOLL in people with Stroke, run by aptaTargets S.L. at 1 site in Spain.
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 19 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 17 Mar 2022. 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 Spain. 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 Adverse Events as assessed by CTCAE v4.0 (time frame: From dosing to follow-up (day 15 after dosing)). The study lists 3 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 NCT04742062, which also lists 1 linked publication.
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 17 Mar 2022; AzTrials last refreshed its copy on 8 Nov 2026.