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Clinical Trial Results:
Safety of tenofovir alafenamide (TAF) in patients with a history of tubulopathy on tenofovir disoproxil fumarate (TDF)

Summary
EudraCT number	2016-003345-29
Trial protocol	GB
Global end of trial date	21 Jul 2023

Results information
Results version number	v1(current)
This version publication date	13 May 2026
First version publication date	13 May 2026
Other versions
Summary report(s)	FANTA CSR

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

3568

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

King's College Hospital NHS Foundation Trust

Sponsor organisation address

Denmark Hill, London, United Kingdom, SE5 9RS

Public contact

Dr Frank Post, Kings College Hospital NHS Foundation Trust, +44 2078485779, frank.post@kcl.ac.uk

Scientific contact

Dr Frank Post, Kings College Hospital NHS Foundation Trust, +44 2078485779, frank.post@kcl.ac.uk

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

21 Jul 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Jul 2023

Global end of trial reached?

Yes

Global end of trial date

21 Jul 2023

Was the trial ended prematurely?

Main objective of the trial

To evaluate the renal and bone safety of TAF in patients with a history of tubulopathy/Fanconi syndrome while receiving TDF Primary endpoint • Between study arm difference in change from baseline to week 12 in retinol-binding protein/creatinine ratio (RBPCR) Secondary endpoints • Incidence of tubulopathy in the TAF/FTC exposed population (through week 96) • Between study arm difference in change from baseline in: o Renal function and bone turnover markers (week 4, 12) • Change from baseline in the TAF/FTC exposed population: o Renal function and bone turnover markers (week 24, 48, 72, 96) o Bone mineral density (week 48, 96)

Protection of trial subjects

All randomised subjects should remain in follow-up for the duration of the trial for the specified study visits, irrespective of whether or not they continue on their allocated treatment arm, unless the subject withdraws consent from the study, when they will return to routine clinical care and non-study commercial drug supply. All study subjects should be encouraged to continue to attend all study visits and complete all study procedures. If a patient withdraws from the study, data already collected may be used for the analyses unless the patient specifically requests that his/her data are removed from the database.

Background therapy

DESCOVY (TAF) is a novel formulation of tenofovir with an approximately 90% reduced systemic tenofovir exposure. Clinical trials have demonstrated high efficacy and an improved safety profile of TAF vs. TDF in terms of changes in eGFR and tubular proteinuria . This study aims to examine the safety of DESCOVY in patients with a history of TDF-associated renal tubular disease under careful monitoring of kidney function and with evaluation of bone mineral density DESCOVY has shown to be safe in patients with mild to moderate renal impairment (CrCl 30-69 mL/min). Establishing the safety of DESCOVY in those previously affected by TDF would help formulate novel regimens with enhanced efficacy, tolerability or convenience for these patients and inform monitoring strategies for those in rich countries and resource limited settings alike.

Evidence for comparator

Actual start date of recruitment

01 Dec 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 31

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

The number of patients screened not specified in CSR, only provided those randomised which the value that was used to populate this.

Number of subjects started

36 ^[1]

Number of subjects completed

Reason: Number of subjects

Did not meet the inclusion criteria: 4

Reason: Number of subjects

Consent withdrawn by subject: 1

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: We do not count screening participants as enrolled

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Open-label on either of the two arms: Arm 1: Immediate initiation of DESCOVY, one tablet daily, with investigator-selected NNRTI/PI/INSTI and discontinuation of abacavir, lamivudine/emtricitabine and entecavir or other hepatitis B drugs as appropriate Arm 2: Deferred initiation (at week 12) of DESCOVY ( 10 or 25mg), one tablet daily, with investigator-selected NNRTI/PI/INSTI and discontinuation of abacavir, lamivudine/emtricitabine and entecavir or other hepatitis B drugs as appropriate

Are arms mutually exclusive

Yes

Immediate initiation arm

Arm description

Immediate initiation of DESCOVY, one tablet daily, with investigator-selected NNRTI/PI/INSTI and discontinuation of abacavir, lamivudine/emtricitabine and entecavir or other hepatitis B drugs as appropriate

Arm type

Experimental

Investigational medicinal product name

DESCOVY

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Immediate initiation of DESCOVY (10mg/200mg if currently regimen contains ritonavir or cobicistat; 25mg/200mg if current regimen does not contain ritonavir or cobicistat), one tablet daily, with continued use* of current NNRTI/PI/INSTI and discontinuation of abacavir, lamivudine/emtricitabine, and entecavir or other hepatitis B drugs as appropriate (*changes in NNRTI/PI/INSTI are allowed after week 12)

Deferred initiation (at week 12) of DESCOVY

Arm description

Deferred initiation (at week 12) of DESCOVY ( 10 or 25mg), one tablet daily, with investigator-selected NNRTI/PI/INSTI and discontinuation of abacavir, lamivudine/emtricitabine and entecavir or other hepatitis B drugs as appropriate

Arm type

Active comparator

Investigational medicinal product name

DESCOVY

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

DESCOVY (10mg/200mg if currently regimen contains ritonavir or cobicistat; 25mg/200mg if current regimen does not contain ritonavir or cobicistat), one tablet daily, with continued use* of current NNRTI/PI/INSTI and discontinuation of abacavir, lamivudine/emtricitabine, and entecavir or other hepatitis B drugs as appropriate (*changes in NNRTI/PI/INSTI are allowed after week 12)

Number of subjects in period 1	Immediate initiation arm	Deferred initiation (at week 12) of DESCOVY
Started	17	14
Completed	15	13
Not completed	2	1
Discontinued treatment	2	-
Transient HIV viraemia (200 – 1000 copies/mL)	-	1

Baseline characteristics

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Reporting group title

Overall trial

Reporting group description

Reporting group values	Overall trial	Total
Number of subjects	31	31
Age categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	0	0
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	29	29
Elderly (≥65 years)	2	2
Gender categorical
Units: Subjects
Female	1	1
Male	30	30

End points

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Reporting group title

Immediate initiation arm

Reporting group description

Reporting group title

Deferred initiation (at week 12) of DESCOVY

Reporting group description

Primary: Cases of recurrent tubulopathy

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End point title

Cases of recurrent tubulopathy ^[1]

End point description

End point type

Primary

End point timeframe

From randomisation to end of follow-up

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Please see uploaded report

End point values	Immediate initiation arm	Deferred initiation (at week 12) of DESCOVY
Number of subjects analysed	17	14
Units: cases	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Randomisation to end of follow-up

Assessment type

Systematic

Dictionary name

Not specified in CSR

Dictionary version

N/A

Reporting group title

Immediate initiation arm

Reporting group description

Reporting group title

Deferred initiation (at week 12) of DESCOVY

Reporting group description

Serious adverse events	Immediate initiation arm	Deferred initiation (at week 12) of DESCOVY
Total subjects affected by serious adverse events
subjects affected / exposed	9 / 17 (52.94%)	2 / 14 (14.29%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Injury, poisoning and procedural complications
Fractures
subjects affected / exposed	1 / 17 (5.88%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Alcohol withdrawal symptoms
subjects affected / exposed	1 / 17 (5.88%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Acute pancreatitis
subjects affected / exposed	1 / 17 (5.88%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chest infection, Pneumonia, Respiratory failure, Exacerbation of COPD
subjects affected / exposed	2 / 17 (11.76%)	1 / 14 (7.14%)
occurrences causally related to treatment / all	0 / 7	0 / 11
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Cellulitis, Abscess
subjects affected / exposed	2 / 17 (11.76%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Suicidal ideation
subjects affected / exposed	1 / 17 (5.88%)	0 / 14 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Right hip pain, Torn Achilles tendon
subjects affected / exposed	1 / 17 (5.88%)	1 / 14 (7.14%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Immediate initiation arm	Deferred initiation (at week 12) of DESCOVY
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 17 (100.00%)	14 / 14 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma, Polycythaemia
subjects affected / exposed	2 / 17 (11.76%)	0 / 14 (0.00%)
occurrences all number	2	0
Vascular disorders
Hypertension
subjects affected / exposed	2 / 17 (11.76%)	2 / 14 (14.29%)
occurrences all number	2	2
Surgical and medical procedures
Tooth Extraction, CT guided nerve root block
subjects affected / exposed	0 / 17 (0.00%)	2 / 14 (14.29%)
occurrences all number	0	2
General disorders and administration site conditions
Chills, Tiredness, Fatigue, Fever, Temperature, Leg Swelling
subjects affected / exposed	4 / 17 (23.53%)	1 / 14 (7.14%)
occurrences all number	5	1
Immune system disorders
Hayfever
subjects affected / exposed	1 / 17 (5.88%)	0 / 14 (0.00%)
occurrences all number	1	0
Reproductive system and breast disorders
Nipple pain, Itching foreskin, Testicular pain , Swollen penis head
subjects affected / exposed	2 / 17 (11.76%)	2 / 14 (14.29%)
occurrences all number	2	2
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders
Additional description: Dental abscess, Root Canal, Flu, Cold, Cough, Oral thrush, Asthma, Chest infection, Coryzal symptoms, Tonsillitis, Nose bleeding, Upper respiratory tract infection, Breathlessness, Dental work, Sinus infection, Infective exacerbation COPD, Epitaxis
subjects affected / exposed	10 / 17 (58.82%)	11 / 14 (78.57%)
occurrences all number	27	22
Psychiatric disorders
Low mood, Vivid dreams, Memory problems, Depression, Concentration difficulties, Insomnia
subjects affected / exposed	1 / 17 (5.88%)	5 / 14 (35.71%)
occurrences all number	1	9
Investigations
Deranged UPCR / UACR, Abnormal LFTs
subjects affected / exposed	2 / 17 (11.76%)	0 / 14 (0.00%)
occurrences all number	2	0
Injury, poisoning and procedural complications
Fall on stairs, Pain post fall, Aches from fall, Bike accident
subjects affected / exposed	0 / 17 (0.00%)	3 / 14 (21.43%)
occurrences all number	0	4
Cardiac disorders
Atypical chest pain, Fainting episode
subjects affected / exposed	0 / 17 (0.00%)	2 / 14 (14.29%)
occurrences all number	0	2
Nervous system disorders
Nervous system disorders
Additional description: Dizziness Peripheral neuropathy Headache Leg numbness Transient global amnesia Worsening short term memory Blackouts Seizures *Daytime somnolence
subjects affected / exposed	6 / 17 (35.29%)	6 / 14 (42.86%)
occurrences all number	6	11
Ear and labyrinth disorders
Labyrinthitis
subjects affected / exposed	0 / 17 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	1
Eye disorders
Floater left eye, Lens of eye opacification, Genetic peripheral retinal atrophy, MSSA Eyes
subjects affected / exposed	4 / 17 (23.53%)	0 / 14 (0.00%)
occurrences all number	4	0
Gastrointestinal disorders
Gastrointestinal disorders
Additional description: Heartburn, Gastroenteritis, Diarrhoea, Nausea, Norovirus, Vomiting, Cramping, Aphthous ulcer, Stomach discomfort, Hemorrhoids, Stool darkening, Mouth dryness, Looser stool, Gastritis, Constipation, Lower abdominal discomfort, Abdominal bloating
subjects affected / exposed	8 / 17 (47.06%)	8 / 14 (57.14%)
occurrences all number	12	19
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders
Additional description: Skin infection Cellulitis Seborrheic warts Ingrown hair Dermatitis Nail infection Psoriasis Rash Cyst Multiple small wounds Sporotrichosis Echtym / MSSA Night sweats Itchiness no rash *Back lump
subjects affected / exposed	6 / 17 (35.29%)	5 / 14 (35.71%)
occurrences all number	15	5
Renal and urinary disorders
Renal and urinary disorders
Additional description: Haematuria Urinary frequency Urinary tract infection Kidney pain Acute urinary retention Renal stones Benign prostatic hypertrophy Nocturia *Drop>25% in eGFR
subjects affected / exposed	4 / 17 (23.53%)	7 / 14 (50.00%)
occurrences all number	5	9
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorders
Additional description: Left flank pain Back pain Knee pain Shoulder pain Hip pain Finger pain Joint pain Gout Osteopenia Bilateral sacroiliitis Sciatica Strained tendon Weakness Torn knee cartilage *Arthralgia
subjects affected / exposed	9 / 17 (52.94%)	11 / 14 (78.57%)
occurrences all number	15	22
Infections and infestations
Infections and infestations
Additional description: Gonorrhoea (throat) Non-gonoccocal urethritis Possible Syphilis Tooth infection Rectal chlamydia Right lower gum infection Viral URTI Genital, Oral, Perianal HSV *Pharyngeal candida
subjects affected / exposed	2 / 17 (11.76%)	7 / 14 (50.00%)
occurrences all number	3	13
Metabolism and nutrition disorders
Metabolism and nutritional disorders
Additional description: Vitamin D deficiency Folate deficiency Hypercho- lesterolaemia Mixed hyper- lipidemia Glucose intolerance Weight gain *Low plasma folate
subjects affected / exposed	1 / 17 (5.88%)	5 / 14 (35.71%)
occurrences all number	1	8

More information

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Were there any global substantial amendments to the protocol? No

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
Safety of tenofovir alafenamide (TAF) in patients with a history of tubulopathy on tenofovir disoproxil fumarate (TDF)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Cases of recurrent tubulopathy

Primary: Cases of recurrent tubulopathy

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: Safety of tenofovir alafenamide (TAF) in patients with a history of tubulopathy on tenofovir disoproxil fumarate (TDF)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Cases of recurrent tubulopathy

Primary: Cases of recurrent tubulopathy

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Safety of tenofovir alafenamide (TAF) in patients with a history of tubulopathy on tenofovir disoproxil fumarate (TDF)