Complement Mediated DiseasesPhase 1NCT03316521
First-In-Human Clinical Study of the C3 Complement Inhibitor AMY- 101 in Healthy Male Volunteers
A Phase 1 study testing AMY-101 in people with Complement Mediated Diseases, run by Amyndas Pharmaceuticals S.A. at 1 site in United States.
Trial summary
Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. A prospective, single-center, open-label, First-In-Human (FIH) clinical study in healthy male volunteers. Read more about this study
- Who is it for?
- Ages 18 to 60 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Complement Mediated Diseases
- What is being tested?
- AMY-101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Apr 2017to 30 Nov 2017
- 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 60 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Willing and able to give written informed consent for participation in the study.
- Healthy male subject aged 18-60 years, inclusive at the time of signing the informed consent.
- Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 and weight at least 50 kg.
- Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
- Willing to use condom and contraceptive methods with a failure rate of < 1% to prevent pregnancy and drug exposure of a partner and to refrain from donating sperm from the date of dosing until three (3) months after dosing of the IMP.
- Willing and able to complete all procedures according to the Protocol.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- History of any Neisseria meningitidis infection
- History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within the last 60 days prior to dosing.
- History of latent or active tuberculosis, as assessed by the investigator based on chest X-ray and positive Quantiferon-TB Gold test.
- History of complement deficiency.
- History of any type of malignancy. However, completely resolved minor malignancies, at the discretion of the Investigator, may not be an exclusion criterion (for example: Non-Melanoma Skin Cancer).
Show all 28Show fewer
- Diagnosis of autoimmune, immunologic or rheumatologic disease (eg, systemic lupus erythematosus, rheumatoid arthritis).
- Any clinically significant illness, medical/surgical procedure or trauma within four (4) weeks of the administration of IMP.
- High CRP at screening (> 0.5 mg/dL).
- Current evidence or history of bacterial, viral or fungal infection within 14 days prior to (first) dosing or longer according to the judgment of the investigator for e.g. viral infections including herpes simplex or herpes zoster.
- Any current condition or risk, which, in the opinion of the Investigator, may interfere with the subject's participation in the study, poses an added risk for the subject, or confounds the assessment of the subject or outcome of the study
- Any clinically significant abnormality in clinical chemistry, hematology, or urinalysis results at the time of screening, as judged by the Investigator.
- Any positive result on screening for serum hepatitis B surface antigen, hepatitis C antibody and/or Human Immunodeficiency Virus (HIV).
- After 10 minutes supine rest abnormal vital signs defined as any of the following:
- Systolic BP > 140 mm Hg
- Diastolic BP > 95 mm Hg
- HR < 40 or > 90 beats per minute
- Prolonged QTcF (>450 ms), cardiac arrhythmias or any clinically significant abnormality in the resting ECG, as judged by the Investigator.
- Any history of any allergy/hypersensitivity or anaphylactic reaction or on-going allergy/hypersensitivity. History of hypersensitivity to antibiotics or drugs with a similar chemical structure or class to AMY-101.
- Use of any prescribed or non-prescribed medication including antacids, analgesics, herbal remedies, vitamins and minerals within two (2) weeks prior to the administration of IMP, except the occasional intake of paracetamol/acetominophen (maximum 2000 mg/day; and not exceeding 3000 mg/week) or nasal decongestant without cortisone or antihistamine, at the discretion of the Investigator.
- Administration of another new chemical entity (defined as a compound that has not been approved for marketing) or having participated in any other clinical study that included drug treatment within 30 day or 5 half lives of the last administration of the other IMP. Subjects consented and screened but not dosed in previous phase I studies are not excluded.
- Immunization with a live-attenuated vaccine one (1) month prior to the first administration of IMP.
- Current smokers or users of nicotine products. Irregular use of nicotine (e.g. smoking, snuffing, chewing tobacco) less than three (3) times per week is allowed before screening visit.
- History of alcohol abuse or excessive intake of alcohol, as judged by the Investigator.
- Positive screen for drugs of abuse at screening or on admission to the unit or positive screen for alcohol at screening or on admission to the unit prior to administration of the IMP.
- Use of anabolic steroids.
- Plasma donation within one (1) month of screening or any blood donation/blood loss > 450 mL during the three (3) months prior to screening.
- Investigator considers the subject unlikely to comply with study procedures, restrictions and requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
HighPoint Clinical Trials Center
High Point, North Carolina, 27265
About this study
Official title: Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the Complement Inhibitor AMY-101. A Prospective, Single-center, Open-label, First-In-Human (FIH) Clinical Study in Healthy Male Volunteers
Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. A prospective, single-center, open-label, First-In-Human (FIH) clinical study in healthy male volunteers.
Read the detailed description
AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central "functional hub" that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.
This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The study is a prospective, single-center, open-label evaluation in healthy male volunteers.
- Conditions
- Complement Mediated Diseases
- Being tested
- AMY-101
- Keywords
- complement inhibition, C3 complement inhibitor, AMY-101, Compstatin Cp40, Paroxysmal Nocturnal Hemoglobinuria (PNH), C3 glomerulopathy (C3G), Periodontal disease, Age-related macular degeneration (AMD), ABO incompatible kidney transplantation
- Medical subject headings
- Hemoglobinuria, Paroxysmal, Periodontal Diseases, Macular Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMY-101Drug
AMY-101 is a selective inhibitor of complement activation, which binds to the complement component C3.
| Study group | Role | What they receive |
|---|---|---|
| Single Ascending Dose (SAD) | Experimental | In the SAD arm subjects will be sequentially included in one of up to six cohorts (dose levels). All cohorts will include at least four subjects each. Additional subjects may be added in any cohort if necessary.
AMY-101 will be administered as a SQ or IV injection. Subjects in each cohort will be dosed sequentially, to allow for close safety monitoring. Between each cohort, safety data will be analyzed, evaluated and reviewed by the internal Safety Review Committee. Subsequent dose levels will be administered until either the maximum tolerated dose (MTD) or the study maximum dose (SMD) is reached based on specified dose escalation criteria. Receives: Drug: AMY-101 |
| Multiple Dose (MD) | Experimental | Depending on the results of the SAD, multiple doses of AMY-101 will be administered at the dose which has been identified as the dose which saturates target C3, for a duration that results to an exposure level equivalent to the maximum exposure achieved in the SAD. The dose and dosing interval will be determined based on the PK data obtained in the SAD part of the study. Each MD cohort will include at least four subjects and may be expanded with additional subjects if necessary. Between each cohort, safety data will be analyzed, evaluated and reviewed by the internal Safety Review Committee. Receives: Drug: AMY-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: Up to 21 days after treatment.
Secondary outcomes (16)
Area under the plasma concentration time curve (AUCt) after a single dose
Measured: Up to 14 days after treatment.
Area under the plasma concentration time curve from zero to infinity (AUC 0->∞) after a single dose
Measured: Up to 14 days after treatment.
Peak Plasma Concentration (Cmax) after single and multiple doses
Measured: Up to 14 days after treatment.
Time to Cmax (Tmax) after single and multiple doses
Measured: Up to 14 days after treatment.
Terminal elimination rate constant (lambdaz) after single and multiple doses
Measured: Up to 14 days after treatment.
Terminal half-life (T1/2) after single and multiple doses
Measured: Up to 14 days after treatment.
Total apparent clearance of drug from plasma/serum (CL/F) after single and multiple doses
Measured: Up to 14 days after treatment.
Volume of distribution (Vz) / fraction of drug absorbed (F) after single and multiple doses
Measured: Up to 14 days after treatment.
Area under the curve at steady state (AUCss) after multiple doses
Measured: Up to 14 days after treatment.
Activation of the classical complement pathway
CH50
Measured: Up to 14 days after treatment.
Activation of the alternative complement pathway
AP50
Measured: Up to 14 days after treatment.
Complement protein C3 plasma levels
Measured: Up to 14 days after treatment.
Complement protein C4 plasma levels
Measured: Up to 14 days after treatment.
Measurement of immune response (plasma protein electrophoresis - IgG,IgA, IgM) after single and multiple administrations of AMY-101.
Measured: Up to 14 days after treatment.
Investigation for anti-drug antibodies after single and multiple administrations of AMY-101.
Measured: Up to 14 days after treatment.
Measurement of lymphocyte subsets after multiple administrations of AMY-101.
Measured: Up to 14 days after treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2017
- Study start24 Apr 2017
- Primary completion30 Nov 2017
- Study completion30 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (16)Papers the sponsor has linked to this study.
- Other trials for Complement Mediated DiseasesStudies 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
- Model description
- This is a prospective, single-center, open-label FIH study investigating the safety, tolerability, PK and PD after single and multiple doses of AMY-101 in healthy male volunteers. In the SAD part of the study, a single dose at ascending dose levels of AMY-101 will be administered to different cohorts, following a careful dose-escalation strategy. In the MD part of the study, multiple doses will be administered using different dosing intervals; the cohorts will include a minimum of four (4) subjects each. Additional subjects may be added in the cohorts if necessary.
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amyndas Pharmaceuticals S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03316521
- Sponsor's protocol ID
- AMY-101/01
- Status last verified
- Jan 2018
- First submitted
- 11 Aug 2017
- Last updated
- 16 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol. 2013 Apr 15;190(8):3839-47. doi: 10.4049/jimmunol.1203200.
PubMed 23564578Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013 Apr 15;190(8):3831-8. doi: 10.4049/jimmunol.1203487.
PubMed 23564577Mastellos DC, Yancopoulou D, Kokkinos P, Huber-Lang M, Hajishengallis G, Biglarnia AR, Lupu F, Nilsson B, Risitano AM, Ricklin D, Lambris JD. Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention. Eur J Clin Invest. 2015 Apr;45(4):423-40. doi: 10.1111/eci.12419. Epub 2015 Mar 9.
PubMed 25678219Ricklin D, Lambris JD. Therapeutic control of complement activation at the level of the central component C3. Immunobiology. 2016 Jun;221(6):740-6. doi: 10.1016/j.imbio.2015.06.012. Epub 2015 Jun 10.
PubMed 26101137Reis ES, Mastellos DC, Yancopoulou D, Risitano AM, Ricklin D, Lambris JD. Applying complement therapeutics to rare diseases. Clin Immunol. 2015 Dec;161(2):225-40. doi: 10.1016/j.clim.2015.08.009. Epub 2015 Sep 1.
PubMed 26341313Mastellos DC, Ricklin D, Hajishengallis E, Hajishengallis G, Lambris JD. Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention. Mol Oral Microbiol. 2016 Feb;31(1):3-17. doi: 10.1111/omi.12129. Epub 2015 Oct 7.
PubMed 26332138Reis ES, DeAngelis RA, Chen H, Resuello RR, Ricklin D, Lambris JD. Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters. Immunobiology. 2015 Apr;220(4):476-82. doi: 10.1016/j.imbio.2014.10.026. Epub 2014 Nov 3.
PubMed 25468722Mastellos DC, Ricklin D, Yancopoulou D, Risitano A, Lambris JD. Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape. Expert Rev Hematol. 2014 Oct;7(5):583-98. doi: 10.1586/17474086.2014.953926. Epub 2014 Sep 2.
PubMed 25213458Risitano AM, Ricklin D, Huang Y, Reis ES, Chen H, Ricci P, Lin Z, Pascariello C, Raia M, Sica M, Del Vecchio L, Pane F, Lupu F, Notaro R, Resuello RR, DeAngelis RA, Lambris JD. Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. Blood. 2014 Mar 27;123(13):2094-101. doi: 10.1182/blood-2013-11-536573. Epub 2014 Feb 4.
PubMed 24497537Mastellos DC, Reis ES, Yancopoulou D, Hajishengallis G, Ricklin D, Lambris JD. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage. Immunobiology. 2016 Oct;221(10):1046-57. doi: 10.1016/j.imbio.2016.06.013. Epub 2016 Jun 16.
PubMed 27353192Maekawa T, Briones RA, Resuello RR, Tuplano JV, Hajishengallis E, Kajikawa T, Koutsogiannaki S, Garcia CA, Ricklin D, Lambris JD, Hajishengallis G. Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3. J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.
PubMed 26728318Hajishengallis G, Maekawa T, Abe T, Hajishengallis E, Lambris JD. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches. Adv Exp Med Biol. 2015;865:57-74. doi: 10.1007/978-3-319-18603-0_4.
PubMed 26306443Hajishengallis G, Hajishengallis E, Kajikawa T, Wang B, Yancopoulou D, Ricklin D, Lambris JD. Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application. Semin Immunol. 2016 Jun;28(3):285-91. doi: 10.1016/j.smim.2016.03.006. Epub 2016 Mar 24.
PubMed 27021500Zhang Y, Shao D, Ricklin D, Hilkin BM, Nester CM, Lambris JD, Smith RJ. Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3 glomerulopathy. Immunobiology. 2015 Aug;220(8):993-8. doi: 10.1016/j.imbio.2015.04.001. Epub 2015 May 5.
PubMed 25982307Mastellos DC, Reis ES, Ricklin D, Smith RJ, Lambris JD. Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery. Trends Immunol. 2017 Jun;38(6):383-394. doi: 10.1016/j.it.2017.03.003. Epub 2017 Apr 14.
PubMed 28416449
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the Complement Inhibitor AMY-101. A Prospective, Single-center, Open-label, First-In-Human (FIH) Clinical Study in Healthy Male Volunteers
- ClinicalTrials.gov ID
- NCT03316521
- Acronym / sponsor ID
- AMY-101/01
- Conditions
- Complement Mediated Diseases
- Keywords
- complement inhibition, C3 complement inhibitor, AMY-101, Compstatin Cp40, Paroxysmal Nocturnal Hemoglobinuria (PNH), C3 glomerulopathy (C3G), Periodontal disease, Age-related macular degeneration (AMD)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Amyndas Pharmaceuticals S.A.Industry (pharma, biotech, devices)
- Study start
- 24 Apr 2017 (actual)
- Primary completion
- 30 Nov 2017 (actual)
- Study completion
- 30 Nov 2017 (actual)
- First posted
- 20 Oct 2017 (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.
Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. A prospective, single-center, open-label, First-In-Human (FIH) clinical study in healthy male volunteers.
Detailed description
AMYNDAS is developing a novel peptidic complement inhibitor AMY-101, based on the third-generation compstatin analogue Cp40. AMY-101 is a selective inhibitor of complement activation in humans and in NHP. It binds to the complement component C3, the central "functional hub" that controls the upstream activation/amplification and downstream effector functions of complement. By binding to C3, AMY-101 inhibits the cleavage of native C3 to its active fragments C3a and C3b. As a consequence, the deposition of C3b, amplification via the alternative pathway and all downstream complement responses are prevented. AMY-101 is being developed to treat complement-mediated diseases, which are largely driven by aberrant C3 activation.
This first-in-human study of the C3-targeting complement inhibitor AMY-101 investigates the safety and PK/PD profile of AMY-101 in healthy male volunteers after Single Ascending Dose (SAD) and Multiple Doses (MD) using subcutaneous (SQ) or intravenous (IV) administration. The study is a prospective, single-center, open-label evaluation in healthy male volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a prospective, single-center, open-label FIH study investigating the safety, tolerability, PK and PD after single and multiple doses of AMY-101 in healthy male volunteers. In the SAD part of the study, a single dose at ascending dose levels of AMY-101 will be administered to different cohorts, following a careful dose-escalation strategy. In the MD part of the study, multiple doses will be administered using different dosing intervals; the cohorts will include a minimum of four (4) subjects each. Additional subjects may be added in the cohorts if necessary.
| Arm | Type | Receives |
|---|---|---|
| Single Ascending Dose (SAD) | Experimental | Drug: AMY-101In the SAD arm subjects will be sequentially included in one of up to six cohorts (dose levels). All cohorts will include at least four subjects each. Additional subjects may be added in any cohort if necessary. AMY-101 will be administered as a SQ or IV injection. Subjects in each cohort will be dosed sequentially, to allow for close safety monitoring. Between each cohort, safety data will be analyzed, evaluated and reviewed by the internal Safety Review Committee. Subsequent dose levels will be administered until either the maximum tolerated dose (MTD) or the study maximum dose (SMD) is reached based on specified dose escalation criteria. |
| Multiple Dose (MD) | Experimental | Drug: AMY-101Depending on the results of the SAD, multiple doses of AMY-101 will be administered at the dose which has been identified as the dose which saturates target C3, for a duration that results to an exposure level equivalent to the maximum exposure achieved in the SAD. The dose and dosing interval will be determined based on the PK data obtained in the SAD part of the study. Each MD cohort will include at least four subjects and may be expanded with additional subjects if necessary. Between each cohort, safety data will be analyzed, evaluated and reviewed by the internal Safety Review Committee. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Willing and able to give written informed consent for participation in the study.
- Healthy male subject aged 18-60 years, inclusive at the time of signing the informed consent.
- Body Mass Index (BMI) ≥ 18 and ≤ 30 kg/m2 and weight at least 50 kg.
- Clinically normal medical history, physical findings, vital signs, ECG and laboratory values at the time of screening, as judged by the Investigator.
- Willing to use condom and contraceptive methods with a failure rate of < 1% to prevent pregnancy and drug exposure of a partner and to refrain from donating sperm from the date of dosing until three (3) months after dosing of the IMP.
Key exclusion criteria (28 listed)
- History of any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
- History of any Neisseria meningitidis infection
- History of unexplained, recurrent infection, or infection requiring treatment with systemic antibiotics within the last 60 days prior to dosing.
- History of latent or active tuberculosis, as assessed by the investigator based on chest X-ray and positive Quantiferon-TB Gold test.
- History of complement deficiency.
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 |
|---|---|---|
| AMY-101AMY-101 is a selective inhibitor of complement activation, which binds to the complement component C3. | Drug | Multiple Dose (MD), Single Ascending Dose (SAD) |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: Up to 21 days after treatment.
16 secondary outcomes
Area under the plasma concentration time curve (AUCt) after a single dose
Time frame: Up to 14 days after treatment.
Area under the plasma concentration time curve from zero to infinity (AUC 0->∞) after a single dose
Time frame: Up to 14 days after treatment.
Peak Plasma Concentration (Cmax) after single and multiple doses
Time frame: Up to 14 days after treatment.
Time to Cmax (Tmax) after single and multiple doses
Time frame: Up to 14 days after treatment.
Terminal elimination rate constant (lambdaz) after single and multiple doses
Time frame: Up to 14 days after treatment.
Terminal half-life (T1/2) after single and multiple doses
Time frame: Up to 14 days after treatment.
Total apparent clearance of drug from plasma/serum (CL/F) after single and multiple doses
Time frame: Up to 14 days after treatment.
Volume of distribution (Vz) / fraction of drug absorbed (F) after single and multiple doses
Time frame: Up to 14 days after treatment.
Area under the curve at steady state (AUCss) after multiple doses
Time frame: Up to 14 days after treatment.
Activation of the classical complement pathway
Time frame: Up to 14 days after treatment.
Activation of the alternative complement pathway
Time frame: Up to 14 days after treatment.
Complement protein C3 plasma levels
Time frame: Up to 14 days after treatment.
Complement protein C4 plasma levels
Time frame: Up to 14 days after treatment.
Measurement of immune response (plasma protein electrophoresis - IgG,IgA, IgM) after single and multiple administrations of AMY-101.
Time frame: Up to 14 days after treatment.
Investigation for anti-drug antibodies after single and multiple administrations of AMY-101.
Time frame: Up to 14 days after treatment.
Measurement of lymphocyte subsets after multiple administrations of AMY-101.
Time frame: Up to 14 days after treatment.
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 16 Jan 2018.
- Background: PubMed 23564578Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol. 2013 Apr 15;190(8):3839-47. doi: 10.4049/jimmunol.1203200.
- Background: PubMed 23564577Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013 Apr 15;190(8):3831-8. doi: 10.4049/jimmunol.1203487.
- Background: PubMed 25678219Mastellos DC, Yancopoulou D, Kokkinos P, Huber-Lang M, Hajishengallis G, Biglarnia AR, Lupu F, Nilsson B, Risitano AM, Ricklin D, Lambris JD. Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention. Eur J Clin Invest. 2015 Apr;45(4):423-40. doi: 10.1111/eci.12419. Epub 2015 Mar 9.
- Background: PubMed 26101137Ricklin D, Lambris JD. Therapeutic control of complement activation at the level of the central component C3. Immunobiology. 2016 Jun;221(6):740-6. doi: 10.1016/j.imbio.2015.06.012. Epub 2015 Jun 10.
- Background: PubMed 26341313Reis ES, Mastellos DC, Yancopoulou D, Risitano AM, Ricklin D, Lambris JD. Applying complement therapeutics to rare diseases. Clin Immunol. 2015 Dec;161(2):225-40. doi: 10.1016/j.clim.2015.08.009. Epub 2015 Sep 1.
- Background: PubMed 26332138Mastellos DC, Ricklin D, Hajishengallis E, Hajishengallis G, Lambris JD. Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention. Mol Oral Microbiol. 2016 Feb;31(1):3-17. doi: 10.1111/omi.12129. Epub 2015 Oct 7.
- Background: PubMed 25468722Reis ES, DeAngelis RA, Chen H, Resuello RR, Ricklin D, Lambris JD. Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters. Immunobiology. 2015 Apr;220(4):476-82. doi: 10.1016/j.imbio.2014.10.026. Epub 2014 Nov 3.
- Background: PubMed 25213458Mastellos DC, Ricklin D, Yancopoulou D, Risitano A, Lambris JD. Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape. Expert Rev Hematol. 2014 Oct;7(5):583-98. doi: 10.1586/17474086.2014.953926. Epub 2014 Sep 2.
- Background: PubMed 24497537Risitano AM, Ricklin D, Huang Y, Reis ES, Chen H, Ricci P, Lin Z, Pascariello C, Raia M, Sica M, Del Vecchio L, Pane F, Lupu F, Notaro R, Resuello RR, DeAngelis RA, Lambris JD. Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. Blood. 2014 Mar 27;123(13):2094-101. doi: 10.1182/blood-2013-11-536573. Epub 2014 Feb 4.
- Background: PubMed 27353192Mastellos DC, Reis ES, Yancopoulou D, Hajishengallis G, Ricklin D, Lambris JD. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage. Immunobiology. 2016 Oct;221(10):1046-57. doi: 10.1016/j.imbio.2016.06.013. Epub 2016 Jun 16.
- Background: PubMed 26728318Maekawa T, Briones RA, Resuello RR, Tuplano JV, Hajishengallis E, Kajikawa T, Koutsogiannaki S, Garcia CA, Ricklin D, Lambris JD, Hajishengallis G. Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3. J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.
- Background: PubMed 26306443Hajishengallis G, Maekawa T, Abe T, Hajishengallis E, Lambris JD. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches. Adv Exp Med Biol. 2015;865:57-74. doi: 10.1007/978-3-319-18603-0_4.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
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 AMY-101 in people with Complement Mediated Diseases, run by Amyndas Pharmaceuticals S.A. at 1 site in United States.
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 6 inclusion and 28 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 16 Jan 2018. 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 States. 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. 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?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: Up to 21 days after treatment.). 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 NCT03316521, which also lists 16 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 16 Jan 2018.