An Extension Protocol for Virologically Suppressed Subjects Who Successfully Completed PRO140_CD03 Study

Status

Terminated

Phases

Phase 2Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05271370

Enrollment

Registered

2022-03-09

Start date

2017-08-29

Completion date

2022-07-10

Last updated

2025-10-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV-1-infection

Brief summary

This study is a Phase 2b/3 multi-center extension study designed to evaluate the long term antiviral activity, safety, and tolerability of the strategy of continuing PRO 140 350mg, 525mg, or 700mg SC (subcutaneous) monotherapy to maintain viral suppression after initial 48 weeks in virologically suppressed subjects. Consenting subjects will continue weekly PRO 140 350mg, 525mg, or 700mg monotherapy during the Treatment Extension Phase with the one-week overlap of existing retroviral regimen and PRO 140 350mg, 525mg, or 700 mg at the end of the treatment in subjects who do not experience virologic failure.

Detailed description

The objective is to assess the long-term safety of using PRO 140 350mg, 525mg, or 700mg SC as single-agent maintenance therapy for the chronic suppression of CCR5-tropic HIV-1 infection.

Interventions

DRUGPRO 140 350

Pro140 SC injection 350 mg

DRUGPRO 140 525

525 mg

DRUGPRO 140 700

700 mg

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Open Label

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Subjects who have completed 48 weeks of treatment in PRO140\_CD03 study. 2. Last known Plasma HIV-1 RNA \< 50 copies/mL within PRO140\_CD03 study. 3. Both male and female patients and their partners of childbearing potential must agree to use 2 medically accepted methods of contraception (e.g., barrier contraceptives \[male condom, female condom, or diaphragm with a spermicidal gel\], hormonal contraceptives \[implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings\], and intrauterine devices) during the course of the study (excluding women who are not of childbearing potential and men who have been sterilized). Females of childbearing potential must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test prior to receiving the first dose of study drug. 4. Willing and able to participate in all aspects of the study, including use of SC medication, completion of subjective evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing written informed consent.

Exclusion criteria

1. Not currently enrolled in PRO140\_CD03 study. 2. Any active infection or malignancy requiring acute therapy (with the exception of local cutaneous Kaposi's sarcoma). 3. Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study. 4. Subjects weighing \< 35kg. 5. History of anaphylaxis to any oral or parenteral drugs. 6. History of Bleeding Disorder or patients on anti-coagulant therapy (except aspirin). Note: Subjects with well-controlled bleeding disorder while on stable anti-coagulant therapy dose with documented stable INRs can be enrolled as per discretion of the Investigator. 7. Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy.

Design outcomes

Primary

Measure	Time frame	Description
Long Term Clinical Safety of PRO 140 Monotherapy by Assessing the Number of Participants With Grade 2, 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale, and the Number of Participants With Treatment-emergent Serious Adverse Events.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	The Division of AIDS (DAIDS) grading table provides an adverse event severity grading scale ranging from grades 1 to 5 with descriptions for each adverse event based on the following general guidelines: * Grade 1 indicates a mild event * Grade 2 indicates a moderate event * Grade 3 indicates a severe event * Grade 4 indicates a potentially life-threatening event * Grade 5 indicates death (Note: This grade is not specifically listed on each page of the grading table). Treatment-Emergent Serious Adverse Events (TESAEs) are defined as serious adverse events with an onset on or after the first treatment.
Proportion of Participants Experiencing Virologic Failure for All Subjects Within Each Treatment Group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	Virological failure is defined as two consecutive HIV-1 RNA levels of ≥ 200 copies/mL for all subjects and within each treatment group.

Secondary

Measure	Time frame	Description
Time to Virologic Failure After Initiating PRO 140 Monotherapy for All Subjects Within Each Treatment Group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	Virological failure (VF) is defined as two consecutive HIV-1 RNA levels of ≥ 200 copies/mL for all subjects and within each treatment group. The date of VF event is defined as the date of the second assessment of the two (2) consecutive HIV-1 RNA levels of \>= 200 copies/mL when virological failure is confirmed. Subjects who did not have VF, the last visit date will be used as the date of the event.
Proportion of Participants Achieving Viral Re-suppression After Experiencing Virologic Failure Within Each Treatment Group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	Viral re-suppression is defined as having HIV-1 RNA levels of \< 50 copies/mL after experiencing virologic failure within each treatment group.
Time to Achieving Viral Re-suppression After Experiencing Virologic Failure Within Each Treatment Group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	Viral re-suppression is defined as having HIV-1 RNA levels of \< 50 copies/mL after experiencing virologic failure within each treatment group.
Proportion of Virologic Failure Subjects Achieving Viral Re-suppression With Re-initiation of Previous Baseline Antiretroviral Regimen Within Each Treatment Group.	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	Viral re-suppression is defined as having HIV-1 RNA levels of \< 50 copies/mL after experiencing virologic failure within each treatment group. Subjects who experienced virologic failure during the treatment phase had an option to re-initiate their PRO 140 regimen to their previous baseline or dose escalate to the next dose level.
Mean Change in CD4 Cell Count, at Each Visit Within the Treatment Phase for All Subjects Within Each Treatment Group	From TE1 (first treatment administration) to last treatment visit, up to 197 weeks	The change from baseline in CD4 cell count was summarized for each visit during the treatment phase for each treatment group. The time-weighted mean of change of the post baseline (visit TE1) values was calculated. The time-weighted mean was adjusted AUC (area under the curve) by time.

Countries

United States

Participant flow

Participants by arm

Arm	Count
PRO 140 350 mg PRO 140 350mg weekly SQ injection. PRO 140 350: Pro140 SC injection 350 mg	8
PRO 140 525 mg PRO 140 525mg weekly SQ injection. PRO 140 525: 525 mg	18
PRO 140 700 mg PRO 140 700mg weekly SQ injection. PRO 140 700: 700 mg	30
Total	56

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Study early termination	8	16	29

Baseline characteristics

Characteristic	PRO 140 350 mg	PRO 140 525 mg	PRO 140 700 mg	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	1 Participants	2 Participants	4 Participants
Age, Categorical Between 18 and 65 years	7 Participants	17 Participants	28 Participants	52 Participants
Age, Continuous	59.88 years STANDARD_DEVIATION 8.37	47.17 years STANDARD_DEVIATION 11.94	47.77 years STANDARD_DEVIATION 13.1	49.30 years STANDARD_DEVIATION 12.9
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	4 Participants	5 Participants	9 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants	14 Participants	25 Participants	47 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Black or African American	1 Participants	2 Participants	4 Participants	7 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	7 Participants	13 Participants	26 Participants	46 Participants
Region of Enrollment United States	8 participants	18 participants	30 participants	56 participants
Sex: Female, Male Female	1 Participants	3 Participants	0 Participants	4 Participants
Sex: Female, Male Male	7 Participants	15 Participants	30 Participants	52 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	1 / 8	1 / 18	0 / 30
other Total, other adverse events	6 / 8	9 / 18	18 / 30
serious Total, serious adverse events	3 / 8	5 / 18	2 / 30

Outcome results

Primary

Long Term Clinical Safety of PRO 140 Monotherapy by Assessing the Number of Participants With Grade 2, 3 or 4 Adverse Events as Defined by the DAIDS Adverse Event Scale, and the Number of Participants With Treatment-emergent Serious Adverse Events.

The Division of AIDS (DAIDS) grading table provides an adverse event severity grading scale ranging from grades 1 to 5 with descriptions for each adverse event based on the following general guidelines: * Grade 1 indicates a mild event * Grade 2 indicates a moderate event * Grade 3 indicates a severe event * Grade 4 indicates a potentially life-threatening event * Grade 5 indicates death (Note: This grade is not specifically listed on each page of the grading table). Treatment-Emergent Serious Adverse Events (TESAEs) are defined as serious adverse events with an onset on or after the first treatment.